Вы находитесь на странице: 1из 269

The common cold in children: Clinical features and diagnosis

Author:
Diane E Pappas, MD, JD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 25, 2015.

INTRODUCTION The common cold is an acute, self-limiting viral infection of the upper
respiratory tract, involving, to variable degrees, sneezing, nasal congestion and discharge
(rhinorrhea), sore throat, cough, low grade fever, headache, and malaise. It can be caused
by members of several families of viruses; the most common are the more than 100
serotypes of rhinoviruses.

The common cold is the most frequent human illness. An estimated 25 million individuals
seek medical care for uncomplicated upper respiratory tract infections (URI) annually in
the United States [1,2]. Approximately 30 percent of these visits result in a prescription for
antibiotics. Inaccurate perceptions that colds are caused by bacteria and that antibiotics
improve outcome fuel the number of visits and requests for antibiotics [3]. Infants and
children are affected more often and experience more prolonged symptoms than adults.
The common cold accounts for approximately 22 million missed days of school and 20
million absences from work, including parents time away from work while caring for ill
children [2,4].

The epidemiology, clinical features, complications, and diagnosis of the common cold in
children will be discussed here. The treatment and prevention of the common cold in
children and the common cold in adults are discussed separately. (See "The common cold
in children: Management and prevention" and "The common cold in adults: Diagnosis and
clinical features" and "The common cold in adults: Treatment and prevention".)

VIROLOGY The symptoms of the common cold can be caused by a variety of viruses.
Rhinoviruses, which include more than 100 serotypes, cause up to 50 percent of colds in
children and adults [2]. Other common causes of colds in preschool children include
respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses, and
adenoviruses (table 1). (See "Epidemiology and clinical manifestations of adenovirus
infection" and "Epidemiology, clinical manifestations, and pathogenesis of rhinovirus
infections" and "Seasonal influenza in children: Clinical features and diagnosis", section on
'Clinical features' and "Parainfluenza viruses in children", section on 'Clinical
presentation' and "Respiratory syncytial virus infection: Clinical features and diagnosis",
section on 'Clinical manifestations'.)

Cold symptoms also can be caused by nonpolio enteroviruses (echoviruses and


coxsackieviruses), coronaviruses, and human metapneumovirus [5-7]. (See "Clinical
manifestations and diagnosis of enterovirus and parechovirus
infections" and "Coronaviruses" and "Human metapneumovirus infections".)

Many of the viruses that cause colds also cause other characteristic clinical syndromes in
children [7]:

RSV Bronchiolitis in children younger than the age of two years (see "Bronchiolitis
in infants and children: Clinical features and diagnosis", section on 'Clinical
features' and "Respiratory syncytial virus infection: Clinical features and diagnosis",
section on 'Clinical manifestations')
Influenza viruses Influenza, pneumonia, and croup (see "Seasonal influenza in
children: Clinical features and diagnosis", section on 'Clinical features')
Parainfluenza viruses Croup (see "Croup: Clinical features, evaluation, and
diagnosis", section on 'Clinical presentation' and "Parainfluenza viruses in children",
section on 'Clinical presentation')
Coxsackievirus A (an enterovirus) Herpangina (fever and ulcerated papules on the
posterior oropharynx) (see "Clinical manifestations and diagnosis of enterovirus and
parechovirus infections", section on 'Herpangina' and "Hand, foot, and mouth disease
and herpangina: An overview", section on 'Herpangina')
Other nonpolio enteroviruses Aseptic meningitis (see "Viral meningitis: Clinical
features and diagnosis in children", section on 'Clinical features')
Adenoviruses Pharyngoconjunctival fever (palpebral conjunctivitis, watery eye
discharge, and pharyngeal erythema) (see "Epidemiology and clinical manifestations
of adenovirus infection")
Human metapneumovirus Pneumonia and bronchiolitis [5,6] (see "Human
metapneumovirus infections", section on 'Children')

Immune response Rhinoviruses, adenoviruses, influenza viruses, and enteroviruses


produce lasting immunity, but immunity does little to prevent subsequent colds because
there are so many serotypes. RSV, parainfluenza viruses, and coronaviruses do not
produce lasting immunity [7,8]. Reinfection may occur, but subsequent infection with the
same agent is generally milder and of shorter duration.

EPIDEMIOLOGY

Seasonal patterns The common cold may occur at any time of year, but there is
typically a high prevalence during the fall and winter months as the different viruses move
through the community in a predictable manner. In the northern hemisphere, this yearly
epidemic begins with an increase in the number of rhinovirus infections in September [9],
followed by parainfluenza viruses in October and November. The winter months are
characterized by an increase in respiratory syncytial virus (RSV), influenza viruses, and
coronaviruses [10]. Adenovirus infections are continuously present at a low rate throughout
the common cold season. The epidemic finally ends with a small wave of rhinovirus
infections in March and April [11]. Enteroviruses most often cause illness in the summer,
but can be detected throughout the year.

Transmission Viruses that cause colds are spread by three mechanisms [7]:

Hand contact: Self-inoculation of ones own conjunctivae or nasal mucosa after


touching a person or object contaminated with cold virus
Inhalation of small particle droplets that become airborne from coughing (droplet
transmission)
Deposition of large particle droplets that are expelled during sneezing and land on
nasal or conjunctival mucosa (typically requires close contact with an infected person)

The most successful means of viral spread for the majority of upper respiratory infections
(URI), including rhinoviruses, is transmission of infectious secretions from contaminated
fingers and hands to the mucous membranes of the nose or eyes of a susceptible recipient
[12]. The risk of person-to-person transfer is dependent upon the amount of time people
spend together, the proximity of their contact with one another, and the amount of virus
shed by the infected patient. In experimental studies, rhinovirus was efficiently transferred
from hand-to-hand after minimal contact (10 seconds) and subsequent contact with nasal
or conjunctival mucosa resulted in infection [13]. Particle aerosols were an inefficient
method of rhinovirus transmission [13,14]. However, both influenza virus and coronavirus
can be transmitted via aerosols. (See "Seasonal influenza in children: Clinical features and
diagnosis", section on 'Transmission' and "Coronaviruses", section on 'Epidemiology'.)

Substantial titers of rhinovirus are present in nasal secretions of infected individuals. Low
titers of rhinovirus are present in saliva in approximately one-half of infected individuals.
Viral contamination of the hands of infected individuals is common. Rhinoviruses may
remain viable on human skin for as long as two hours [15]. Rhinoviruses also can survive
for up to one day on inanimate surfaces although porous materials such as tissues and
cotton handkerchiefs do not appear to support virus survival [15-18].

Surface contamination of pediatric office toys with respiratory viral RNA does not appear to
be an important method of transfer. In an observational study, approximately 20 percent of
the toys in a pediatric office waiting room were contaminated with picornavirus RNA
(rhinovirus or enterovirus). Cleaning with a disposable germicidal wipe (containing
quaternary ammonium with alcohol) was only modestly effective in removing the viral RNA,
but transfer from the toys to the fingers was inefficient [19].

Period of infectivity Viral shedding peaks on the third day after inoculation; this
coincides with a peak in symptoms [20,21]. In experimental studies, viral titers in nasal
washings returned to near baseline values by five days after inoculation [20]. Low levels of
viral shedding may persist for up to two weeks.

Incubation period The incubation period (time between contact with infectious material
until the onset of symptoms) for most common cold viruses is 24 to 72 hours.

PATHOPHYSIOLOGY Symptoms of the common cold are largely due to the innate
immune response to infection, rather than to direct viral damage to the respiratory tract
[22]. After deposition on nasal or conjunctival mucosa, cold viruses attach to receptors on
epithelial cells in the nasopharynx and enter the cells [7]. During rhinovirus infection, viral
replication occurs in only a small number of nasal epithelial cells [23,24]. The infected cells
release cytokines, including interleukin (IL)-8, which attracts polymorphonuclear cells
(PMNs) [25-27]. Large numbers of PMNs (100-fold increase) accumulate in the nasal
secretions and mucociliary clearance is slowed [28].

Symptoms usually appear one to two days after viral inoculation, coinciding with the influx
of PMNs in the nasal submucosa and epithelium [28-30]. The severity of symptoms
correlates with mucosal IL-8 concentrations. A change in the character of the nasal
discharge from clear to yellow/white or green correlates with the increase in PMNs, but not
with an increase in positive bacterial cultures [31]. The colored discharge may signify the
presence of PMNs (yellow or white) or of PMN enzymatic activity (green color).

By an unknown mechanism, rhinovirus infection increases vascular permeability in the


nasal submucosa, releasing albumin and kinins (bradykinin), which may then contribute to
the symptoms of the common cold [28,32]. Bradykinin causes rhinitis and sore throat when
sprayed into the noses of volunteers [33]. Histamine concentration does not increase in
experimental rhinovirus infection [28,32]. (See "Epidemiology, clinical manifestations, and
pathogenesis of rhinovirus infections".)

Histologic studies in young adults with natural and experimentally induced colds
demonstrate that the nasal epithelium remains intact, although there is an influx of PMNs
into the nasal submucosa and epithelium [29,30]. In vitro, rhinoviruses and coronaviruses
do not cause gross destruction of nasal epithelial cells; however, adenoviruses and
influenza A have a cytopathic effect, with resultant destruction of nasal epithelial cells [34].

CLINICAL FEATURES

Frequency and duration Children younger than six years have an average of six to
eight colds per year (up to one per month, September through April), with a typical
symptom duration of 14 days [2,35,36]. Young children in daycare appear to have more
colds than children cared for at home. However, when they enter primary school, children
who attended daycare are less vulnerable to colds than those who did not [37,38].
Older children and adults have an average of two to four colds per year, with a typical
symptom duration of five to seven days [2,11]. The duration of symptoms is increased
among cigarette smokers [39].

Symptoms and signs

Overview The symptom profile of the common cold varies from patient to patient, in
part due to age, and in part due to the causative virus, although the wide range and
overlapping manifestations of the various cold-causing viruses make it impossible to
determine the specific causative virus without laboratory testing [2,8,36].

In infants, fever and nasal discharge are common manifestations. Additional


manifestations may include fussiness, difficulty feeding, decreased appetite, and difficulty
sleeping.

In school-aged children, nasal congestion, nasal discharge and cough are the predominant
symptoms. In a prospective study of 81 colds in school-aged children (5 to 12 years),
parents recorded signs and symptoms during the first 10 days of illness [36]. Signs and
symptoms included cough, sneeze, feverish (defined as ill-appearing, flushed, warm to
touch), congestion, nasal discharge, and headache; sore throat and hoarseness were not
evaluated. Rhinovirus RNA was detected in 46 percent of episodes. The frequency and
duration of the various manifestations were as follows (figure 1):

Nasal congestion was reported in 59 percent at the onset of illness, peaked (88
percent) on day 3, and persisted in 75 percent on day 7
Runny nose peaked (72 percent) on day 3 and persisted in 50 percent on day 6
Cough was reported in 46 percent at onset, peaked (69 percent) on day 1, and
persisted in 50 percent on day 8
Sneezing was reported in 36 percent at the onset of illness, peaked (55 percent) on
day 1, and persisted in 35 percent on day 6
Feverishness was reported in 15 percent at the onset of illness and declined over
the first three days
Headache was reported in 15 percent at the onset of illness, 20 percent on day 1,
and approximately 15 percent through day 4

Approximately three-quarters of children remained symptomatic on day 10 of illness.

Fever Fever may be the predominant manifestation of the common cold during the
early phase of infection in young children. It is uncommon in older children and adults.
(See "The common cold in adults: Diagnosis and clinical features", section on 'Clinical
features'.)
New onset of fever or recurrence of fever (if one was present at the onset of illness) may
indicate secondary bacterial infection (eg, acute otitis media, sinusitis, pneumonia).
(See 'Complications' below.)

Nasal manifestations Nasal congestion, nasal discharge, and sneezing are common
in children [36]. Examination may reveal erythema and swelling of the nasal mucosa and
nasal discharge. Nasal discharge may be clear initially, but often becomes colored (yellow
or green) within a few days [7]. Coloring of the nasal discharge is probably related to the
increase in number or enzymatic activity of polymorphonuclear cells [31]. Coloring of the
nasal discharge does not indicate bacterial superinfection or acute bacterial sinusitis
[2,31]. (See 'Pathophysiology' above.)

Acute bacterial sinusitis may be indicated by persistence of nasal discharge for more than
10 days without improvement, severe symptoms, or worsening symptoms (as defined
below). (See 'Sinusitis' below.)

Cough Cough occurs in more than two-thirds of children with the common cold and
may be the most bothersome symptom for the childs caregivers [36,40]. Cough may affect
the childs sleep, school performance, and ability to play; it also may disturb the sleep of
other family members and be disruptive in the classroom [41]. The cough may linger for an
additional week or two after other symptoms have resolved, but should gradually improve.
Diagnoses other than the common cold should be considered if the cough worsens or fails
to improve. (See 'Differential diagnosis' below.)

Other symptoms and signs Other symptoms and signs of the common cold may
include sore throat (typically an early manifestation), hoarseness, headache, irritability,
difficulty sleeping, decreased appetite, anterior cervical adenopathy, and conjunctival
injection. Vomiting and diarrhea are uncommon [2,7,36].

Middle ear abnormalities Middle ear abnormalities are common during the course of
an uncomplicated cold [42,43]. In an observational study of 86 children (2 to 12 years) with
colds, two-thirds had abnormal middle ear pressure (assessed by tympanometry) at some
point during the two weeks after onset [42]. Abnormal middle ear pressures were most
common during the first week. They shifted from ear to ear and were present only
intermittently during the course of the cold.

Abnormal middle ear pressure may predispose to the development of acute otitis media.
The development of acute otitis media is not affected by treatment with combination
decongestant-antihistamines [44]. (See 'Acute otitis media' below.)

The cause of abnormal middle ear pressure during the common cold is unknown. Viral
nasopharyngitis may result in Eustachian tube dysfunction and abnormal middle ear
pressure, or abnormal middle ear pressure may result from the viral infection of the
mucosa of the middle ear and/or Eustachian tube.
Radiographic features Self-limiting radiographic abnormalities of the paranasal
sinuses are common during the course of an uncomplicated cold:

In a study of 31 healthy young adults with the recent onset of cold symptoms,
abnormalities of the paranasal sinuses were evident on computed tomographic (CT)
scans during the acute phase of illness in 27 (87 percent) [45]. Antibiotics were not
administered, and follow-up CT scans two weeks later showed complete resolution or
marked improvement in 11 of the 14 subjects evaluated (79 percent).
In another study, 37 (62 percent) of 60 children (4 to 7 years old) with a cold had
major abnormalities (more than one-third volume loss or air-fluid level) in their
maxillary and/or ethmoid sinuses by magnetic resonance imaging (MRI). Twenty-six
of the 37 had a follow-up MRI at two weeks; 30 percent had a new cold and two had
received an antibiotic. At follow-up, the major abnormalities were no longer present in
54 percent of ethmoid and 65 percent of maxillary sinuses [46].

It is unknown whether these abnormalities are the result of impaired sinus drainage or the
result of actual viral infection of the sinus mucosa. Nose blowing has been demonstrated
to propel nasal secretions into the paranasal sinuses [47]. However, the degree to which
this contributes to the accumulation of fluid in the sinuses is uncertain.

COMPLICATIONS

Acute otitis media The majority of children with a cold have abnormal middle ear
pressure at some point during its course. (See 'Middle ear abnormalities' above.) Abnormal
middle ear pressure may predispose to acute otitis media (AOM).

The risk of secondary acute otitis media is greatest among children 6 to 11 months of age
[7]. Approximately one-third to one-half of colds in young children are complicated by
development of AOM as defined by acute onset of symptoms, inflammation of the
tympanic membrane, and fluid in the middle ear [48-50]. However, bacterial or suppurative
otitis media, defined as a bulging tympanic membrane with purulent material behind it or
purulent otorrhea from perforation of the tympanic membrane [51], occurs in only 5 to 19
percent of colds in young children [50]. In a prospective study, the frequency of AOM was
increased among children who had middle ear effusion before they developed the cold
[50].

AOM may be indicated by new-onset fever and earache after the first few days of cold
symptoms. (See "Acute otitis media in children: Diagnosis", section on
'Diagnosis' and "Acute otitis media in children: Epidemiology, microbiology, clinical
manifestations, and complications", section on 'Clinical manifestations'.)

Asthma exacerbation Viral upper respiratory infections (URI) commonly are


associated with wheezing in susceptible children and are associated with at least 50
percent of asthma exacerbations in children. (See "Asthma in children younger than 12
years: Initial evaluation and diagnosis", section on 'Respiratory tract infections'.)

Sinusitis Viral URI is the most important risk factor for the development of bacterial
sinusitis. Between 6 and 13 percent of viral URIs in children are complicated by acute
bacterial sinusitis [49]. (See "Acute bacterial rhinosinusitis in children: Clinical features and
diagnosis", section on 'Predisposing factors'.)

Secondary bacterial infection of the paranasal sinuses may be indicated by (see "Acute
bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Clinical
features'):

Persistent nasal symptoms without improvement for more than 10 days, or


Severe symptoms (temperature 39C [102.2F], ill-appearance, purulent nasal
discharge for three to four days), or
Worsening symptoms (exacerbation of nasal discharge or cough, new onset fever,
or recurrence of fever)

Lower respiratory tract disease Bacterial pneumonia is an uncommon complication of


the common cold. It may be indicated by new-onset fever after the first few days of cold
symptoms. Prolonged cough in the absence of a new fever may signify viral lower
respiratory tract infection. (See "Community-acquired pneumonia in children: Clinical
features and diagnosis", section on 'Clinical presentation'.)

Other complications Other complications of the common cold in children may include
epistaxis, conjunctivitis, and pharyngitis. (See "Epidemiology and etiology of epistaxis in
children", section on 'Mucosal irritation' and "Conjunctivitis", section on 'Viral
conjunctivitis' and "Group A streptococcal tonsillopharyngitis in children and adolescents:
Clinical features and diagnosis", section on 'Viral infections'.)

DIAGNOSIS The diagnosis of the common cold is made clinically, based upon history
and examination findings, including exposure to someone with a cold, nasal congestion,
nasal discharge, sore throat, fever (in young children), anterior cervical adenopathy, and
erythema of nasal mucosa and oropharynx [7]. Laboratory tests are not helpful in making
the diagnosis. (See 'Clinical features' above.)

Clinical features that may indicate a diagnosis other than an uncomplicated cold include
persistent fever, high-fever (>39C [102.2F]), ill-appearance, absence of nasal symptoms,
oral mucosal lesions (eg, the posterior vesicles of herpangina), wheezing, focal findings on
lung examination (eg, dullness to percussion, reduced air entry, crackles, bronchial
breathing), hemoptysis, acute onset or difficulty breathing (may suggest inhaled foreign
body), and/or features of a chronic respiratory disorder (eg, failure to thrive, finger
clubbing, over-inflated chest, chest deformity, atopy) [41,52,53]. Chest radiography may be
warranted in children with focal findings on lung examination, relentlessly progressive
cough, hemoptysis, or features of an undiagnosed chronic respiratory disorder [41].
(See 'Complications' above and 'Differential diagnosis' below.)

Laboratory testing can identify the viral pathogen if it is necessary to do so [2]. The wide
range and overlapping manifestations of the various cold-causing viruses make it
impossible to clinically determine the causative virus in an individual patient [2].

DIFFERENTIAL DIAGNOSIS The differential diagnosis of the common cold includes


other causes of rhinitis (allergic, seasonal, vasomotor, rhinitis medicamentosa), acute
bacterial sinusitis, nasal foreign body, inhaled foreign body, pertussis, structural
abnormalities of the nose or sinuses, influenza, and bacterial pharyngitis or tonsillitis
[2,7,41]. These conditions usually can be differentiated from the common cold by history
and physical examination.

Allergic, seasonal, or vasomotor rhinitis; rhinitis medicamentosa Historical features


usually differentiate these disorders from the common cold (eg, previous history,
pattern of onset, exposure, etc) (see "An overview of rhinitis")
Acute bacterial sinusitis Patients with acute bacterial sinusitis may complain of
facial pain; acute bacterial sinusitis is differentiated from the common cold by the
persistence, increased severity, or worsening of symptoms (see "Acute bacterial
rhinosinusitis in children: Clinical features and diagnosis", section on 'Acute bacterial
rhinosinusitis')
Nasal foreign body Clinical features suggestive of nasal foreign body include
unilateral, fetid, purulent, or blood-stained nasal discharge; the foreign body usually
can be seen with anterior rhinoscopy after suctioning purulent secretions
(see "Diagnosis and management of intranasal foreign bodies")
Inhaled foreign body Clinical features suggestive of inhaled foreign body may
include acute onset of cough, a choking episode, monophonic wheezing, and
localized decreased air entry (see "Airway foreign bodies in children", section on
'Presentation')
Pertussis Pertussis classically begins with mild cough and coryza (catarrhal
phase); however the cough gradually increases and becomes paroxysmal
(see "Pertussis infection in infants and children: Clinical features and diagnosis",
section on 'Classic presentation')
Structural abnormalities of the nose or sinuses Structural abnormalities of the
nose or sinuses may result in nasal congestion or stuffiness; these lesions usually are
not associated with other manifestations of the common cold (eg, cough, sore throat,
fever)
Influenza Although influenza virus may cause the common cold, it usually causes
more severe illness; abrupt onset of fever (often >39C [102.2F]), headache,
myalgia, and malaise in addition to cough, sore throat, and rhinitis (see "Seasonal
influenza in children: Clinical features and diagnosis", section on 'Clinical features')
Bacterial pharyngitis or tonsillitis Group A streptococcal tonsillopharyngitis usually
is not accompanied by nasal symptoms, which are the predominant manifestation of
the common cold in children (see "Group A streptococcal tonsillopharyngitis in
children and adolescents: Clinical features and diagnosis", section on 'Clinical
features')

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, The Basics and Beyond the Basics. The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)

Basics topics (see "Patient education: Giving your child over-the-counter medicines
(The Basics)" and "Patient education: Cough in children (The Basics)")
Beyond the Basics topic (see "Patient education: The common cold in children
(Beyond the Basics)")

SUMMARY

The common cold is an acute, self-limiting viral syndrome of the upper respiratory
tract, involving, to variable degrees, sneezing, nasal congestion and discharge, sore
throat, cough, low grade fever, headache, and malaise. (See 'Introduction' above.)
The symptoms of the common cold can be caused by a variety of viruses (table 1).
Rhinoviruses cause up to 50 percent of colds in children and adults. Other common
causes of colds in preschool children include respiratory syncytial virus (RSV),
influenza viruses, parainfluenza viruses, and adenoviruses. (See 'Virology' above.)
The majority of colds are transmitted by hand contact; cold-inducing viruses may
remain viable on human skin for at least two hours and on inanimate surfaces for a
day. (See 'Transmission' above.)
Children younger than six years have an average of six to eight colds per year with
typical symptom duration of 14 days. Nasal congestion, nasal discharge, and cough
are the predominant symptoms (figure 1). Yellow or green coloring of the nasal
discharge does not indicate bacterial superinfection or acute bacterial sinusitis.
(See 'Symptoms and signs' above.)
Abnormal middle ear pressure occurs frequently during the course of the common
cold, particularly during the first week. Radiographic abnormalities of the paranasal
sinuses (rhinosinusitis) also occur frequently during the course of the common cold
and resolves without antibiotic treatment. (See 'Middle ear abnormalities' above
and 'Radiographic features' above.)
Complications of the common cold include acute otitis media, acute bacterial
sinusitis, asthma exacerbation, and lower respiratory tract disease.
(See 'Complications' above.)
The diagnosis of the common cold is made clinically, based upon history and
examination findings, including exposure to someone with a cold, nasal congestion,
nasal discharge, sore throat, fever (in young children), anterior cervical adenopathy,
and erythema of nasal mucosa and oropharynx. Other diagnoses should be
considered if the child has fever >39C (102.2F), ill-appearance, absence of nasal
symptoms, oral mucosal lesions, wheezing, focal findings on lung examination,
hemoptysis, or features of a chronic respiratory disorder (eg, failure to thrive, finger
clubbing, over-inflated chest, chest deformity, atopy). Laboratory tests are not helpful
in making the diagnosis. (See 'Diagnosis' above.)
The differential diagnosis of the common cold includes other causes of rhinitis
(allergic, seasonal, vasomotor, rhinitis medicamentosa), acute bacterial sinusitis,
nasal foreign body, inhaled foreign body, pertussis, structural abnormalities of the
nose or sinuses, influenza, and bacterial pharyngitis or tonsillitis. These conditions
usually can be differentiated from the common cold by history and physical
examination. (See 'Differential diagnosis' above.)

ACKNOWLEDGMENT We are saddened by the death of J. Owen Hendley, MD, who


passed away in May 2015. UpToDate wishes to acknowledge Dr. Hendley's past work as
an author for this topic.

Use of UpToDate is subject to the Subscription and License Agreement.

he common cold in children: Management and prevention

Author:
Diane E Pappas, MD, JD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jan 24, 2017.

INTRODUCTION The common cold is an acute, self-limiting viral infection of the upper
respiratory tract characterized by variable degrees of sneezing, nasal congestion and
discharge (rhinorrhea), sore throat, cough, low grade fever, headache, and malaise.
The management and prevention of the common cold in children will be discussed here.
The epidemiology, clinical features, and diagnosis of the common cold in children and the
common cold in adults are discussed separately. (See "The common cold in children:
Clinical features and diagnosis" and "The common cold in adults: Diagnosis and clinical
features" and "The common cold in adults: Treatment and prevention".)

CAREGIVER EDUCATION The common cold is usually a mild and self-limiting viral
illness, usually caused by rhinoviruses. Caregiver education is the mainstay of
management [1,2] and is recommended by the American Academy of Pediatrics (AAP) [3],
the United Kingdom's National Institute for Health and Care Excellence (NICE) [4,5], and
British Thoracic Guidelines for the assessment and management of cough in children [6].

Antiviral therapy is not available for the viruses that cause the common cold with the
exception of influenza virus. The clinical features of influenza and treatment of influenza
with antiviral agents are discussed separately. (See "Seasonal influenza in children:
Prevention and treatment with antiviral drugs", section on 'Antiviral therapy'.)

Expected course of illness In infants and young children, the symptoms of the
common cold usually peak on day 2 to 3 of illness and then gradually improve over 10 to
14 days (figure 1) [7,8]. The cough may linger in a minority of children, but should steadily
resolve over three to four weeks. In older children and adolescents, symptoms usually
resolve in five to seven days (longer in those with underlying lung disease or who smoke
cigarettes) [9-11].

Indications for re-evaluation Re-evaluation may be warranted if the symptoms


worsen (eg, difficulty breathing or swallowing, high fever) or exceed the expected duration.
Worsening or persistent symptoms (eg, persistent cough) may indicate the development of
complications or the need to consider a diagnosis other than the common cold (eg,
pneumonia, pertussis). (See "The common cold in children: Clinical features and
diagnosis", section on 'Complications' and "The common cold in children: Clinical features
and diagnosis", section on 'Differential diagnosis'.)

Supportive care We generally recommend one or a combination of the following


interventions as first-line therapy for children with the common cold [3,12-16]. Although
most of these interventions have not been studied in randomized trials, they are relatively
inexpensive and unlikely to be harmful [13,15,17].

Maintaining adequate hydration Maintaining adequate hydration may help to


thin secretions and soothe the respiratory mucosa [15].
Ingestion of warm fluids Warm liquids (eg, tea, chicken soup) may have a
soothing effect on the respiratory mucosa, increase the flow of nasal mucus (possibly
also mediated by the inhalation of steam), and loosen respiratory secretions, making
them easier to remove [14,15,18]. The warmed liquids should be appropriate for the
age of the infant or child. (See "Introducing solid foods and vitamin and mineral
supplementation during infancy", section on 'When to initiate complementary
foods' and "Dietary recommendations for toddlers, preschool, and school-age
children", section on 'Dietary guidelines'.)
Topical saline Topical saline may be beneficial, is inexpensive, and is unlikely to
be harmful or impede recovery. The application of saline to the nasal cavity may
temporarily remove bothersome nasal secretions, improve mucociliary clearance, and
lead to vasoconstriction (decongestion) [19]. Side effects may include mucosal
irritation or nosebleed.
In infants, topical saline is applied may with saline nose drops and a bulb syringe
(table 1). In older children, a saline nasal spray or saline nasal irrigation (eg, squeeze
bottle, neti pot, or nasal douche) may be used. It is important that saline irrigants be
prepared from sterile or bottled water; cases of amebic encephalitis associated with
nasal irrigation prepared from tap water have been reported [20]. (See "Free-living
amebas and Prototheca", section on 'Epidemiology'.)
The Centers for Disease Control and Prevention (CDC) provides information about
safe methods for nasal irrigation.
A 2015 systematic review of five randomized trials (including 544 children and 205
adults) concluded that nasal saline irrigation may be beneficial in relieving upper
respiratory infection symptoms [21]. Different outcome measures precluded pooling of
results. In the largest trial, nasal saline irrigation modestly improved symptoms,
decreased use of other therapies, decreased recurrence of symptoms, and
decreased school absence [22].
Humidified air A cool mist humidifier/vaporizer may add moisture to the air to
loosen nasal secretions although this treatment is not well studied [16,23,24]. It is
important to counsel caregivers who use cool mist humidifiers to clean the humidifier
after each use according to the manufacturer's instructions to minimize the risk of
infection or inhalation injury [25-27].
We do not recommend the inhalation of steam or heated humidified air as a treatment
for nasal symptoms in children with the common cold. Inhalation of heated humidified
air or steam does not reduce symptoms and may result in burns [28].
A 2013 systematic review of six randomized trials (394 participants) evaluating the
effects of inhalation of heated humidified air on symptoms of the common cold found
the benefits to be inconsistent [29]. A subsequent randomized trial including 899
patients (3 years) found that advice to use steam inhalation did not reduce
symptoms of acute respiratory infection [30].
The World Health Organization (WHO) suggests that neither steam nor cool mist
therapy be encouraged in the management of a cough or cold [15].

Over-the-counter medications Over-the-counter (OTC) products for symptomatic


relief of the common cold in children include antihistamines, decongestants, antitussives,
expectorants, mucolytics, antipyretics/analgesics, and combinations of these medications
(table 2).
Children <6 years Except for antipyretics/analgesics, OTC medications for the
common cold should be avoided in children <6 years of age [31-33].
6 to 12 years Except for antipyretics/analgesics, we suggest not using OTC
medications for the common cold in children 6 to 12 years of age.
Adolescents 12 years OTC decongestants may provide symptomatic relief of
nasal symptoms in adolescents 12 years. (See 'Nasal symptoms' below.)

In randomized trials, systematic reviews, and meta-analyses, OTC medications have not
been proven to work any better than placebo in children and may have serious side effects
[34-43]. OTC cough and cold medications have been associated with fatal overdose in
children younger than two years [44-46]. OTC medications have the potential for enhanced
toxicity in young children because metabolism, clearance, and drug effects may vary
according to age. Safe dosing recommendations have not been established for children
[17]. (See "Over-the-counter cough and cold preparations: Approach to pediatric
poisoning".)

If parents choose to administer OTC medications to treat the common cold in children >6
years, they should be advised to use single-ingredient medications for the most
bothersome symptom and be provided with proper dosing and administration instructions
to avoid potential toxicity [17]. As an example, inverting the container rather than holding it
upright when administering intranasal medication may provide a dose that is 20 to 30
times greater than recommended [42]. (See 'Symptomatic therapy' below and "Over-the-
counter cough and cold preparations: Approach to pediatric poisoning".)

SYMPTOMATIC THERAPY Symptoms of the common cold need not be treated unless
they bother the child or other family members (eg, interrupting sleep, interfering with
drinking, causing discomfort) [47]. Symptomatic therapies have associated risks and
benefits, particularly in young children (table 2).

Discomfort due to fever We suggest that discomfort due to fever in the first few days
of the common cold be treated with acetaminophen (for children older than three months)
or ibuprofen (for children older than six months) [48]. (See "Fever in infants and children:
Pathophysiology and management", section on 'Management of fever'.)

When suggesting antipyretics and analgesics, it is important for clinicians to counsel


caregivers against the concomitant use of combination over-the-counter (OTC)
medications to avoid overdose from multiple medications that contain the same ingredient
(eg, acetaminophen). (See "Clinical manifestations and diagnosis of acetaminophen
(paracetamol) poisoning in children and adolescents", section on 'Inappropriate dosing by
a caregiver'.)

Nasal symptoms Nasal symptoms include rhinitis and nasal congestion/obstruction.


Nasal obstruction can interfere with drinking and may be the most bothersome symptom in
infants and young children [13].
For first-line therapy of bothersome nasal symptoms, we suggest one or more supportive
interventions (eg nasal suction; saline nasal drops, spray, or irrigation; adequate hydration;
cool mist humidifier) rather than OTC medications or topical aromatic therapies. Although
supportive interventions have not been demonstrated to be effective in randomized trials,
the common cold is a self-limiting illness and supportive interventions are safe and
inexpensive [17]. (See 'Supportive care' above and 'Unproven therapies' below.)

Our second-line interventions for bothersome nasal symptoms that do not improve with
supportive care vary according to age:

<6 years For children <6 years with bothersome nasal symptoms that persist
despite supportive interventions, we generally suggest increasing the frequency of
nasal suction, sprays, or irrigation. We do not use OTC medications for nasal
symptoms in children <6 years. The benefits are unproven and there are associated
risks. (See 'Over-the-counter medications' above.)
Ipratropium nasal spray 0.06% is available by prescription for children older than five
years and may be warranted on a case-by-case basis. Two sprays are administered
to each nostril three times per day for four days.
6 to 12 years For children age 6 to 12 years with bothersome nasal symptoms
that do not respond to supportive interventions, we generally suggest increasing the
frequency of nasal suction, sprays, or irrigation rather than other interventions. We
suggest not using OTC decongestants or decongestant/antihistamine combinations.
The benefits are unproven and there are associated risks [43]. Ipratropium nasal
spray is available by prescription and may be warranted on a case-by-case basis.
The regimen varies according to age:
6 through 11 years Ipratropium 0.06% nasal spray, two sprays in each nostril
three times per day for four days
12 years Ipratropium 0.06% nasal spray, two sprays in each nostril three to
four times per day for four days
In a systematic review of seven randomized trials comparing ipratropium nasal spray
with placebo in children 5 years and adults, ipratropium was effective in reducing
subjective nasal discharge but not nasal congestion [49]. Adverse effects
(nosebleeds, nasal dryness, mouth dryness) were approximately two to four times as
common in patients treated with ipratropium.
12 years For children 12 years with bothersome nasal symptoms that do not
respond to supportive interventions, we suggest OTC decongestants (oral or topical)
or ipratropium nasal spray.
Decongestants (oral or topical) cause vasoconstriction of the nasal mucosa.
We prefer oral pseudoephedrine to phenylephrine and other oral OTC nasal
decongestants. Side effects of oral decongestants may include tachycardia,
elevated diastolic blood pressure, and palpitations [50].
Commonly used topical decongestants include oxymetazoline, xylometazoline,
and phenylephrine [1]. Side effects of topical decongestants include nosebleeds
and drying of the nasal membranes. Topical decongestants should only be used
for two to three days; longer use may result in rebound nasal congestion after
discontinuation [1,13].
A 2016 systematic review found low-quality evidence that multiple doses of
oral and/or topical decongestants subjectively improved nasal congestion in adults
[51]. No studies directly compared oral with topical decongestants. In randomized
trials in adult patients with allergic rhinitis, oral pseudoephedrine was more effective in
reducing nasal congestion than phenylephrine or placebo, whereas phenylephrine
was no more effective than placebo [52-54].

Diagnoses other than the common cold should be considered in children whose nasal
symptoms persist or worsen despite second line interventions. (See 'Persistent
symptoms' below.)

Cough Cough may affect the child's sleep, school performance, and ability to play; it
also may disturb the sleep of other family members and be disruptive in the classroom [6].
Although caregivers frequently seek interventions to suppress cough, they should
understand that cough clears secretions from the respiratory tract and suppression of
cough may result in retention of secretions and potentially harmful airway obstruction
[3,15].

We suggest that airway irritation contributing to cough be relieved with oral hydration,
warm fluids (eg, tea, chicken soup), honey (in children older than one year), or cough
lozenges or hard candy (in children in whom they are not an aspiration risk) rather than
OTC or prescription antitussives, antihistamines, expectorants, or mucolytics. Fluids,
honey, cough lozenges, and hard candy are inexpensive and unlikely to be harmful,
although they may provide only placebo effect [55]. (See 'Unproven therapies' below.)

Oral hydration and warm fluids are discussed above. (See 'Supportive
care' above.)
Honey We suggest honey as an option for treating cough in children 1 year with
the common cold. The honey (2.5 to 5 mL [0.5 to 1 teaspoon]) can be given straight
or diluted in liquid (eg, tea, juice [47]). Corn syrup may be substituted if honey is not
available. Honey has a modest beneficial effect on nocturnal cough and is unlikely to
be harmful in children older than one year of age. Honey should be avoided in
children younger than one year because of the risk of botulism. (See "Botulism",
section on 'Infant botulism'.)
In a randomized trial, 300 children (one to five years of age) with upper respiratory
infection and nocturnal cough were assigned to receive a single dose (10 g) of honey
(eucalyptus, citrus, or labiatae) or placebo (a date extract similar to honey in
appearance and taste) before bedtime; caregivers completed a symptom survey on
the days before and after the intervention; 270 children completed the study [56].
Symptoms improved in all children after the intervention. However, children who
received honey had greater mean improvement in cough frequency (1.77 to 1.85
versus 1.00 points), severity (1.78 to 1.94 versus 0.99 points) and bothersomeness
(2.00 to 2.16 versus 1.25 points) than those who received placebo. Adverse effects
(abdominal pain, nausea, vomiting) occurred in five patients, approximately evenly
distributed among each of the honey and the placebo groups. The findings of this trial
were confirmed in a 2014 systematic review and meta-analysis (mean difference in
cough frequency -1.85, 95% CI -3.36 to -0.33) [57]. Honey also reduced cough
frequency compared with no treatment and diphenhydramine, but not compared
with dextromethorphan.
Given the relative safety and low cost of honey, the World Health Organization (WHO)
and American Academy of Pediatrics (AAP) suggest it as a potential treatment for
upper respiratory infection in young children who are older than one year [15,47].
Lozenges We suggest hard candy or lozenges as an option for treating cough in
children in children in whom they are not an aspiration risk. Although there is no
evidence from controlled trials that cough lozenges and hard candy are effective in
decreasing cough, they are unlikely to be harmful [15]. The AAP suggests that cough
lozenges or hard candy may be used to coat the irritated throat for children older than
six years [47].

We do not use codeine or other antitussive agents (eg, dextromethorphan) for the
treatment of cold-related cough in children. They have potential harms with no proven
benefit [58]. Adverse effects of codeine in children include somnolence, respiratory
depression, and even death [59]; adverse effects of dextromethorphan include behavioral
disturbances and respiratory depression [3].

The AAP recommends against codeine and dextromethorphan-containing medications for


the treatment of cough associated with viral respiratory infections because there are no
well-controlled studies demonstrating efficacy and safety [3,59]. The European Medicines
Agency recommends against codeine to treat cough and cold in children younger than 12
years and in children between 12 and 18 years who have breathing problems (eg, asthma)
[60]. The WHO guidelines recommend against the use of codeine preparations for cough
in children but suggest that dextromethorphan may be warranted in the unusual
circumstance when severe prolonged coughing interferes with feeding or sleeping [15]. In
such cases, a diagnosis other than the common cold should be considered (eg, pertussis,
asthma, pneumonia) [61]. (See "The common cold in children: Clinical features and
diagnosis", section on 'Differential diagnosis' and "Causes of chronic cough in
children" and "Approach to chronic cough in children".)

Sore throat Symptomatic relief of sore throat in children and adolescents is discussed
separately. (See "Sore throat in children and adolescents: Symptomatic treatment".)
Middle ear abnormalities We do not suggest decongestants or decongestant-
antihistamine combinations for symptoms of middle ear abnormalities (eg, conductive
hearing loss) in children with the common cold. Although abnormalities of middle ear
pressure associated with the common cold may predispose to development of acute otitis
media, in a prospective cross-over study, treatment with a decongestant-antihistamine did
not prevent the development of acute otitis media [62]. (See "Acute otitis media in children:
Epidemiology, microbiology, clinical manifestations, and complications", section on
'Pathogenesis'.)

PERSISTENT SYMPTOMS

Persistent nasal symptoms Diagnoses other than the common cold should be
considered in children who have nasal discharge that is more severe or prolonged
than expected with the common cold (eg, persists for more than 10 days without
improvement or is worsening). (See "The common cold in children: Clinical features
and diagnosis", section on 'Differential diagnosis'.)
Alternative diagnoses include:
Nasal foreign body (see "Diagnosis and management of intranasal foreign
bodies")
Allergic rhinitis, nonallergic rhinitis, medication-induced rhinitis (see "An
overview of rhinitis")
Acute bacterial sinusitis (see "Acute bacterial rhinosinusitis in children: Clinical
features and diagnosis")
Persistent cough Diagnoses other than the common cold should be considered
in children who have cough that is more severe or prolonged than expected with the
common cold (eg, persists for more than two weeks without improvement or is
worsening) [61]. Alternative diagnoses include pneumonia, asthma, pertussis, cystic
fibrosis, inhaled foreign body, among others. (See "The common cold in children:
Clinical features and diagnosis", section on 'Differential diagnosis' and "Causes of
chronic cough in children" and "Approach to chronic cough in children".)

UNPROVEN THERAPIES

Antibiotics There is no role for antibiotics in the treatment of the common cold [6].
Antibiotics do not alter the course of the common cold and do not prevent secondary
complications, but may cause significant side effects and contribute to increasing
bacterial antimicrobial resistance [63]. The use of antibiotics should be reserved for
clearly diagnosed secondary bacterial infections, including bacterial otitis media,
sinusitis, and pneumonia. (See "The common cold in children: Clinical features and
diagnosis", section on 'Complications'.)
Antihistamines We do not suggest antihistamines for the treatment of the
common cold. In randomized trials, neither antihistamines nor combination
antihistamine-decongestants have been effective in relieving nasal symptoms or
cough in children with the common cold [35,37,38,64], but these medications may
have adverse effects, including sedation, paradoxic excitability, respiratory
depression, and hallucinations (table 2).
Intranasal glucocorticoids We do not suggest intranasal corticosteroids for the
treatment of nasal symptoms of the common cold. A 2015 systematic review of three
trials (353 participants) found no benefit [65].
Antitussives We do not suggest prescription (codeine) or OTC
(dextromethorphan) antitussive medications to treat cough in children with the
common cold. Their efficacy has not been proven and they have the potential for
enhanced toxicity [3,35,39,44,60,66]. (See "Dextromethorphan abuse and poisoning:
Clinical features and diagnosis", section on 'Epidemiology' and "Opioid intoxication in
children and adolescents", section on 'Clinical manifestations'.)
Expectorants and mucolytics We do not suggest OTC expectorants
(eg, guaifenesin) or mucolytics (eg, acetylcysteine, bromhexine, letosteine) to treat
cough in children with the common cold. Expectorants and mucolytics increase
mucus production and thin respiratory secretions, respectively, to make the secretions
easier to expel [41]. Neither expectorants nor mucolytics are of proven benefit in
children [13,15,41]. By itself, guaifenesin alone is relatively safe, causing only mild
gastrointestinal irritation, but in OTC medications guaifenesin is usually combined
with other ingredients [61]. Adverse effects of mucolytics include bronchospasm,
gastrointestinal disturbance, and fever [15].
Bronchodilators We do not suggest bronchodilators to treat cough in
nonasthmatic children with the common cold. Bronchodilators are not effective for
acute cough in nonasthmatic children [6,67,68]. However, children with asthma who
develop a cold should use their bronchodilator rescue agent as indicated according to
their asthma action plan. (See "Asthma in children younger than 12 years: Rescue
treatment for acute symptoms", section on 'Summary'.)
Aromatic vapors (for external rub) We do not suggest topical
aromatic agents/external rubs (eg, menthol, camphor, eucalyptus oil) for the
treatment of nasal congestion or cough in children with the common cold.
In a randomized crossover trial comparing menthol and eucalyptus oil in 42 healthy
school children, menthol increased the perception of nasal patency, but did not affect
spirometry [69].
In another randomized trial that compared a vapor rub combination (camphor,
menthol, and eucalyptus oils) with petrolatum and no treatment, vapor rub had no
effect on rhinorrhea, but reduced cough severity, improved child and parent sleep,
and reduced a combined symptom score; all outcomes were parent-reported [70].
The vapor rub combination was associated with at least one mild irritant effect in
nearly one-half of children. Because the study was not well blinded (86 percent of
parents applying the vapor rub correctly guessed that they were applying it), the
likelihood of a significant placebo effect cannot be eliminated [71]. In addition, parent
report of cough must be interpreted with caution; parental reporting of the frequency
and severity of cough is unreliable compared with objective measures [72-74].
Vitamins, minerals, and herbal products
Vitamin C We suggest not using vitamin C for the treatment of the common
cold in children. In a 2013 meta-analysis of randomized trials, vitamin C (
200 mg/day) initiated after the onset of symptoms did not reduce the duration
(seven trials, 3249 cold episodes) or severity (four trials, 2708 cold episodes) of
cold symptoms [75]. No serious adverse effects were reported.
Zinc We suggest not using zinc for the treatment of the common cold in
children. The efficacy of zinc in reducing the duration or severity of cold
symptoms in children remains unclear and side effects are common [76].
Although several systematic reviews of randomized trials suggest that zinc may
shorten the duration of cold symptoms, there was significant heterogeneity
among the individual trials [76,77]. In a 2012 systematic review and meta-
analysis of eight trials (934 participants: 371 adults and 563 children), zinc
reduced the duration of symptoms (mean difference -1.65 days, 95% CI -2.5 to
-0.8) [76]. In subgroup analysis, zinc reduced the duration of symptoms in adults
(mean difference -2.63 days, 95% CI -3.69 to -1.58), but not in children (mean
difference -0.26 days, 95% CI -0.78 to 0.25). The effects of zinc also differed by
formulation (zinc acetate was effective; zinc gluconate and zinc sulfate were not)
and dose of ionic zinc (dose of 75 mg were more effective than lower doses).
Adverse effects, including bad taste and nausea, were common and may
contribute to the limited usefulness of zinc in children [76,78].
Zinc nasal products, including homeopathic intranasal zinc gluconate, have been
associated with long-standing or permanent loss of sense of smell and are not
recommended for children [79-81].
Echinacea purpurea We suggest not using Echinacea purpurea for the
treatment of the common cold in children. Several rigorously designed
randomized trials and a meta-analysis of randomized trials in adults found that
echinacea is no better than placebo for the treatment of upper respiratory
infections (URI) [82-85]. Similarly, a randomized trial in children (age 2 to 11
years) found no differences in the duration or severity of URI symptoms in
children treated with echinacea or placebo [86]. However, children treated with
echinacea had an increased rate of rash (7 versus 2.7 percent). (See "Clinical
use of echinacea", section on 'Upper respiratory tract infection'.)
Pelargonium sidoides (Umckaloabo, South African geranium) extract We
suggest not using Pelargonium sidoides extract for the treatment of the common
cold in children. Although a systematic review found one study suggesting that
10 days of therapy was effective in adults, the evidence was very low quality
[87]. Evidence regarding the safety of P. sidoides in children is limited. In pooled
analysis of trials evaluating P. sidoides for the treatment of acute respiratory
infections, adverse events were rarely reported but slightly more common among
recipients of P. sidoides than placebo.

PREVENTION

Child care and school Most children with colds need not be excluded from out-of-
home child care or school because transmission is likely to have occurred before the child
became symptomatic [88]. The risk of spread can be decreased by following common
sense prevention measures, discussed in the following sections.

Hygiene The best methods for preventing transmission of the common cold are
frequent handwashing and avoiding touching one's mouth, nose, and eyes. In
observational studies, alcohol-based hand sanitizers and virucidal hand treatments (eg,
iodine, salicylic acid, pyroglutamic acid) were associated with decreased transmission [89-
91]. (See "The common cold in children: Clinical features and diagnosis", section on
'Transmission'.)

Cold viruses can be transmitted from the hands to objects in the environment or to other
people. To avoid contaminating their hands, children with the common cold can be
instructed to cough into a tissue or the crook of their elbow rather than into their hands.
Used tissues should be discarded in a waste basket.

Disinfectants Decontamination of environmental surfaces with virucidal disinfectants


such as phenol/alcohol (eg, Lysol) may help decrease the rate of transmission of cold-
inducing viruses [92]. Virucidal impregnated nasal tissues also may reduce the
transmission of cold viruses [93-95].

A randomized trial of antibacterial cleaning products versus standard cleaning products in


households with at least one preschool child detected no difference in respiratory
symptoms (runny nose, cough, sore throat) among household members [96]. However,
antibacterial products would not necessarily be expected to be active against viral
pathogens.

Immunizations There is not an immunization to prevent the common cold. However,


there are immunizations to prevent some of the viruses that can cause clinical syndromes
similar to common cold.

Yearly influenza immunization is recommended for all individuals older than six months to
prevent influenza infection and its complications. (See "Seasonal influenza in children:
Prevention with vaccines", section on 'Target groups'.)

Monthly injection of palivizumab (a monoclonal antibody preparation) is recommended to


prevent respiratory syncytial virus (RSV) lower respiratory tract infection in high risk
infants. Prevention of RSV with palivizumab is discussed separately. (See "Respiratory
syncytial virus infection: Prevention", section on 'Immunoprophylaxis'.)
Unproven preventive measures We do not suggest herbal products, vitamins,
minerals, or probiotics to prevent the common cold in children. These agents have not
been proven beneficial and may be harmful.

Herbal products Meta-analyses have not found conclusive evidence


that Echinacea purpurea or Allium sativum (garlic) prevents the common cold in
children [85,97]. (See "Clinical use of echinacea", section on 'Prevention'.)
Vitamin D In randomized trials, neither daily nor monthly administration of vitamin
D reduced the incidence or severity of the common cold in adults; studies in children
are lacking. (See "Vitamin D and extraskeletal health", section on 'Immune system'.)
Vitamin C A 2013 meta-analysis of 24 trials (10,708 participants) found no
evidence that daily vitamin C supplementation prevents the common cold in the
general community (risk ratio [RR] 0.97, 95% CI 0.94-1.00) [75]. However, daily
vitamin C supplementation may shorten the duration of the common cold in children.
In meta-analysis of 14 trials (2530 cold episodes), daily vitamin C (at least
200 mg/day) by children shortened the duration of the common cold by 14 percent
(95% CI 7.3 to 21 percent); no serious adverse effects were reported.
Zinc Although randomized trials indicate that oral zinc may provide some benefit
in preventing colds and decreasing cold duration and severity [98,99], the benefits are
limited by the need for prolonged daily administration (5 months) and adverse
effects including bad taste and nausea.
Probiotics We do not suggest probiotics for the prevention of colds in children. A
2015 meta-analysis of 12 randomized trials in children and adults found low quality
evidence that, compared with placebo, probiotics (various strains of lactobacilli
and Bifidobacterium) reduced the number of subjects who had 1 acute respiratory
infection (odds ratio 0.53, 95% CI 0.37-0.76) and the mean duration of illness (mean
difference 1.89 days, 95% CI 1.75-2.03) [51]. Additional studies are necessary to
confirm these results and determine which doses and strains are most beneficial
before probiotics can be routinely recommended.

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient education: Giving your child over-the-counter medicines
(The Basics)" and "Patient education: Cough in children (The Basics)")
Beyond the Basics topics (see "Patient education: The common cold in children
(Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

The common cold is usually a mild and self-limiting viral illness. Caregiver education
is the mainstay of management and should include information about the expected
course, indications for reevaluation, supportive interventions, the potential dangers of
over-the-counter (OTC) medications for young children, and symptomatic therapy.
(See 'Caregiver education' above.)
In infants and young children, the symptoms of usually peak on day 2 to 3 of illness
and then gradually improve over 10 to 14 days (figure 1). In older children and
adolescents, symptoms usually resolve in five to seven days. Re-evaluation may be
warranted if the symptoms worsen or exceed the expected duration. (See 'Expected
course of illness' above and 'Indications for re-evaluation' above.)
OTC cough and cold medications should be avoided in children <6 years. We
suggest not using OTC cough and cold medications in children between 6 and 12
years of age (Grade 2B). These medications have no proven benefit for children and
may have serious adverse effects (table 2). (See 'Over-the-counter
medications' above.)
Symptomatic therapy may be warranted if the symptoms bother the child (eg,
interrupting sleep, interfering with drinking, causing discomfort) or other family
members. (See 'Symptomatic therapy' above.)
For first-line therapy of bothersome nasal symptoms, we suggest one or more
supportive interventions (eg nasal suction; saline nasal drops, spray, or irrigation;
adequate hydration; cool mist humidifier) rather than OTC medications or topical
aromatic therapies (Grade 2C). (See 'Nasal symptoms' above and 'Unproven
therapies' above.)
Second-line interventions for bothersome nasal symptoms vary according to
age:
-For children <6 years, we generally suggest increasing the frequency of
nasal suction, sprays, or irrigation (Grade 2C).
-For children 6 to 12 years, we generally suggest increasing the frequency
of nasal suction, sprays, or irrigation rather than other interventions (Grade
2C).
-For children 12 years, we suggest either ipratropium nasal spray or OTC
decongestants (oral or topical) (Grade 2C).
We suggest that airway irritation contributing to cough be relieved with oral
hydration, warm fluids (eg, tea, chicken soup), honey (in children older than one
year), or cough lozenges or hard candy (in children in whom they are not an
aspiration risk) rather than OTC or prescription antitussives, antihistamines,
expectorants, or mucolytics (Grade 2C). (See 'Cough' above and 'Unproven
therapies' above.)
Symptomatic relief of sore throat is discussed separately. (See "Sore throat in
children and adolescents: Symptomatic treatment".)
We suggest not using zinc, Echinacea purpurea, or vitamin C for the treatment of
the common cold in children (Grade 2B). (See 'Unproven therapies' above.)
Most children with the common cold need not be excluded from out-of-home child
care or school. The risk of spread can be decreased through frequent hand washing
and appropriate cough hygiene. (See 'Prevention' above.)
We suggest not using Echinacea purpurea, Allium sativum (garlic), vitamin
D, vitamin C, or zinc for the prevention of the common cold in children (Grade 2B).
(See 'Unproven preventive measures' above.)

ACKNOWLEDGMENT We are saddened by the death of J Owen Hendley, MD, who


passed away in May 2015. UpToDate wishes to acknowledge Dr. Hendley's past work as
an author for this topic.

Patient education: The common cold in children (Beyond the Basics)

Author:
Diane E Pappas, MD, JD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Aug 04, 2015.

COMMON COLD OVERVIEW The common cold is the most common illness in the
United States. Infants and children are affected more often and experience more
prolonged symptoms than adults. The common cold accounts for approximately 22 million
missed days of school and 20 million absences from work, including time away from work
caring for ill children.

This topic review discusses the causes, symptoms, and treatment of the common cold in
children. The common cold in adults is discussed separately. (See "Patient education: The
common cold in adults (Beyond the Basics)".)
COMMON COLD CAUSES The common cold is a group of symptoms caused by a
number of different viruses. There are more than 100 different varieties of rhinovirus, the
type of virus responsible for the greatest number of colds. Other viruses that cause colds
include enteroviruses (echovirus and coxsackieviruses) and coronavirus. Because there
are so many viruses that cause the symptoms of the common cold, people may have
multiple colds each year and dozens over a lifetime.

Children under six years average six to eight colds per year (up to one per month,
September through April), with symptoms lasting an average of 14 days. This means that a
child could be ill with intermittent cold symptoms for nearly half of the days in this time
period, without cause for concern. Young children in daycare appear to suffer from more
colds than children cared for at home. However, when day-care children enter primary
school, they catch fewer colds, presumably because they are already immune to a larger
number.

Seasonal patterns The common cold may occur at any time of year, although most
colds occur during the fall and winter months, regardless of the geographic location. Colds
are not caused by cold climates or being exposed to cold air.

Transmission Colds are transmitted from person-to-person, either by direct contact or


by contact with the virus in the environment. Colds are most contagious during the first two
to four days.

Direct contact People with colds typically carry the cold virus on their hands, where it
is capable of infecting another person for at least two hours. If a child with a cold touches
another child or adult, who then touches their eye, nose, or mouth, the virus can later
infect that person.

Infection from particles on surfaces Some cold viruses can live on surfaces (such as
countertops, door handles, or toys) for up to one day.

Inhaling viral particles Droplets containing viral particles can be exhaled into the air by
breathing or coughing. Rhinoviruses are not usually transmitted as a result of contact with
infected droplets, although influenza virus and coronavirus can be transmitted via small
droplets. Cold viruses are not usually spread through saliva.

COMMON COLD SYMPTOMS The signs and symptoms of a cold usually begin one to
two days after exposure. In children, nasal congestion is the most prominent symptom.
Children can also have clear, yellow, or green-colored nasal discharge; fever (temperature
higher than 100.4F or 38C) is common during the first three days of the illness. The table
describes how to take a child's temperature (table 1). (See "Patient education: Fever in
children (Beyond the Basics)".)
Other symptoms may include sore throat, cough, irritability, difficulty sleeping, and
decreased appetite. The lining of the nose may become red and swollen, and the lymph
nodes (glands) in the neck may become slightly enlarged.

The symptoms of a cold are usually worst during the first 10 days. However, some children
continue to have a runny nose, congestion, and a cough beyond 10 days. In addition, it is
not unusual for a child to develop a second cold as the symptoms of the first cold are
resolving; this can make it seem as if the child has a single cold that lasts for weeks or
even months, especially during the fall and winter. This is not a cause for concern, unless
the child has any of the more serious symptoms, discussed below. (See 'When to seek
help' below.)

Symptoms of allergies (allergic rhinitis) are slightly different than those of a cold, and may
include bothersome itching of the nose and eyes.

COMMON COLD COMPLICATIONS Most children who have colds do not develop
complications. However, parents should be aware of the signs and symptoms of potential
complications.

Ear infection Between 5 and 19 percent of children with a cold develop a bacterial or
viral ear infection. If a child develops a fever (temperature higher than 100.4F or 38C)
after the first three days of cold symptoms, an ear infection may be to blame. (See "Patient
education: Ear infections (otitis media) in children (Beyond the Basics)".)

Asthma Colds can cause wheezing in children who have not wheezed before, or
worsening of asthma in children who have a history of this condition.

Sinusitis Children who have nasal congestion that does not improve over the course of
10 days may have a bacterial sinus infection.

Pneumonia Children who develop a fever after the first three days of cold symptoms
may have bacterial pneumonia, especially if the child also has a cough and is breathing
rapidly.

COMMON COLD TREATMENT

Symptomatic treatment The treatment of an infant or child with a cold is different than
treatment recommended for adults. Antihistamines, decongestants, cough medicines, and
expectorants, alone and in combinations, are all marketed for the symptoms of a cold.
However, there have been few clinical trials of these products in infants and children, and
there are no studies that demonstrate any benefit in infants or children.

The United States Food and Drug Administration (FDA) advisory panel has recommended
against the use of these medications in children younger than six [1]. We agree with this
recommendation because these medications are not proven to be effective and have the
potential to cause dangerous side effects. For children older than 6 years, cold
medications may have fewer risks; however, there is still no proven benefit.

Parents may give acetaminophen (sample brand name: Tylenol) to treat a child (older than
three months) who is uncomfortable because of fever during the first few days of a cold.
Ibuprofen (sample brand names: Advil, Motrin) can be given to children older than six
months. Aspirin should not be given to any child under age 18 years. There is no benefit of
these medications if the child is comfortable. Parents should speak with their child's
healthcare provider about when and how to treat fever. (See "Patient education: Fever in
children (Beyond the Basics)".)

Humidified air may improve symptoms of nasal congestion and runny nose. For infants,
parents can try saline nose drops to thin the mucus, followed by bulb suction to temporarily
remove nasal secretions (table 2). An older child may try using a saline nose spray.

Honey may be helpful for nighttime cough in children older than 12 months.

Parents should encourage their child to drink an adequate amount of fluids; it is not
necessary to drink extra fluids. Children often have a reduced appetite during a cold, and
may eat less than usual. If an infant or child completely refuses to eat or drink for a
prolonged period, the parent should contact their child's healthcare provider.

Antibiotics Antibiotics are not effective in treating colds. They may be necessary if the
cold is complicated by a bacterial infection, like an ear infection, pneumonia, or sinusitis.
Parents who think their child has developed one of these infections should contact their
child's healthcare provider.

Inappropriate use of antibiotics can lead to the development of antibiotic resistance, and
can possibly lead to side effects, such as an allergic reaction.

Herbal and alternative treatments A number of alternative products, including zinc,


and herbal products such as echinacea, are advertised to treat or prevent the common
cold. There is some evidence that prophylactic use of vitamin C may decrease the duration
of the common cold in children and adults. With the exception of vitamin C, none of these
treatments have been proven to be effective in clinical trials; their use is not
recommended.

COMMON COLD PREVENTION Simple hygiene measures can help to prevent


infection with the viruses that cause colds. These measures include:

Hand washing is an essential and highly effective way to prevent the spread of
infection. Hands should be wet with water and plain soap, and rubbed together for 15
to 30 seconds. It is not necessary to use antibacterial hand soap. Teach children to
wash their hands before and after eating and after coughing or sneezing.
Alcohol-based hand rubs are a good alternative for disinfecting hands if a sink is not
available. Hand rubs should be spread over the entire surface of hands, fingers, and
wrists until dry, and may be used several times. These rubs can be used repeatedly
without skin irritation or loss of effectiveness.
It may be difficult or impossible to completely avoid people who are ill, although
parents should try to limit direct contact.
Most children with colds need not be excluded from day care or school. It is likely
that they spread the virus before they developed cold symptoms.
Using a household cleaner that kills viruses, such as phenol/alcohol (sample brand
name: Lysol), may help to reduce viral transmission.

WHEN TO SEEK HELP If a child develops any of the following features, the parent
should call their healthcare provider, regardless of the time of day or night.

Refusing to drink anything for a prolonged period


Behavior changes, including irritability or lethargy (decreased responsiveness); this
usually requires immediate medical attention
Difficulty breathing, working hard to breathe, or breathing rapidly; this usually
requires immediate medical attention

Parents should call the healthcare provider if the following symptoms develop, or if there
are general concerns about the child:

Fever greater than 101F (38.4C) lasts more than three days. The table describes
how to take a child's temperature (table 1).
Nasal congestion does not improve or worsens over the course of 14 days.
The eyes become red or develop yellow discharge.
There are signs or symptoms of an ear infection (pain, ear pulling, fussiness).

SUMMARY

The common cold is a group of symptoms caused by a number of different viruses.


Children under six years average six to eight colds per year (up to one per month,
September through April), with symptoms lasting an average of 14 days. This means
that a child could be ill with intermittent cold symptoms for nearly half of the days in
this time period, without cause for concern.
Colds are most contagious during the first two to four days. People with colds
typically carry the cold virus on their hands, where it is capable of infecting another
person for at least two hours. Some cold viruses can live on surfaces (such as
countertops, door handles, or toys) for as long as one day. Droplets containing viral
particles can be exhaled into the air by breathing, coughing, or sneezing.
The signs and symptoms of a cold usually begin one to two days after exposure. In
children, nasal congestion is the most prominent symptom. Children can also have
clear, yellow, or green-colored nasal discharge. Fever (temperature higher than
100.4F or 38C) is common during the first three days of the illness. Other symptoms
may include sore throat, cough, irritability, difficulty sleeping, and decreased appetite.
Most children who have colds do not develop complications. However, parents
should be aware of the signs and symptoms of potential complications, including ear
infections, asthma, sinusitis, and pneumonia.
There have been few clinical trials of cold medications (antihistamines,
decongestants, cough medicines, and expectorants) in infants and children, and there
are no studies that demonstrate any benefit in infants or children. We
do not recommend their use in infants and children because of the lack of proven
efficacy and the potential risk of dangerous side effects.
Parents may give acetaminophen (sample brand name: Tylenol) to children older
than three months or ibuprofen (sample brand names: Advil, Motrin) to children older
than six months to treat discomfort associated with fever. Humidified air can improve
symptoms of nasal congestion and runny nose. Honey may be helpful for nighttime
cough in children older than 12 months.
Parents should encourage their child to drink an adequate amount of fluids; it is not
necessary to drink extra fluids.
Antibiotics are not effective in treating colds. They may be necessary if the cold is
complicated by a bacterial infection, like an ear infection, pneumonia, or sinusitis.
Parents who think their child has developed one of these infections should contact
their child's healthcare provider. Inappropriate use of antibiotics can lead to the
development of antibiotic resistance, and can possibly lead to side effects, such as an
allergic reaction.
A number of alternative products, including zinc, vitamin C, and herbal products
such as echinacea, are advertised to treat or prevent the common cold. None of
these treatments has been proven to be effective in clinical trials; their use is not
recommended.
Simple hygiene measures can help to prevent infection with the viruses that cause
colds, including hand washing or use of an alcohol-based hand rub and limiting
contact with others who are ill.

WHERE TO GET MORE INFORMATION Your healthcare provider is the best source of
information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients).


Related topics for patients, as well as selected articles written for healthcare professionals,
are also available. Some of the most relevant are listed below.

Patient level information UpToDate offers two types of patient education materials.
The Basics The Basics patient education pieces answer the four or five key questions
a patient might have about a given condition. These articles are best for patients who want
a general overview and who prefer short, easy-to-read materials.

Patient education: Cough, runny nose, and the common cold (The Basics)
Patient education: Sore throat in children (The Basics)
Patient education: Sinusitis in adults (The Basics)
Patient education: Giving your child over-the-counter medicines (The Basics)
Patient education: Eustachian tube problems (The Basics)
Patient education: Pneumonia in children (The Basics)
Patient education: Swollen neck nodes in children (The Basics)
Patient education: Adenovirus infections (The Basics)
Patient education: Mycoplasma pneumonia in children (The Basics)
Patient education: Enterovirus D68 (The Basics)

Beyond the Basics Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are best for patients who want in-depth
information and are comfortable with some medical jargon.

Patient education: The common cold in adults (Beyond the Basics)


Patient education: Fever in children (Beyond the Basics)
Patient education: Ear infections (otitis media) in children (Beyond the Basics)

Professional level information Professional level articles are designed to keep


doctors and other health professionals up-to-date on the latest medical findings. These
articles are thorough, long, and complex, and they contain multiple references to the
research on which they are based. Professional level articles are best for people who are
comfortable with a lot of medical terminology and who want to read the same materials
their doctors are reading.

Acute bacterial rhinosinusitis in children: Clinical features and diagnosis


Acute bacterial rhinosinusitis in children: Microbiology and treatment
Approach to the child with recurrent infections
Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis
Epidemiology, clinical manifestations, and pathogenesis of rhinovirus infections
The common cold in adults: Treatment and prevention
The common cold in children: Clinical features and diagnosis
Zinc deficiency and supplementation in children and adolescents
The common cold in children: Management and prevention

The following organizations also provide reliable health information.

National Library of Medicine


(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Allergy and Infectious Diseases
(www.niaid.nih.gov/)
Centers for Disease Control and Prevention (CDC)
Phone: (404) 639-3534
Toll-free: (800) 311-3435
(www.cdc.gov)

ACKNOWLEDGMENT We are saddened by the death of J. Owen Hendley, MD, who


passed away in May 2015. UpToDate wishes to acknowledge Dr. Hendley's past work as
an author for this topic.

[1-6]

OTITIS MEDIA AGUDA

Acute otitis media in children: Epidemiology, microbiology, clinical manifestations,


and complications

Authors:
Jerome O Klein, MD
Stephen Pelton, MD
Section Editors:
Sheldon L Kaplan, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 29, 2016.

INTRODUCTION Acute otitis media (AOM) is defined by moderate to severe bulging of


the tympanic membrane (TM) or new onset of otorrhea not due to acute otitis externa
accompanied by acute signs of illness and signs or symptoms of middle ear inflammation
[1]. (See "Acute otitis media in children: Diagnosis", section on 'Acute otitis media'.)
The epidemiology and microbiology of AOM in the United States have been influenced by
several factors, including:

Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 and


the 13-valent pneumococcal conjugate vaccine in 2010
Publication of guidelines by the American Academy of Pediatrics and the American
Academy of Family Physicians (AAFP) in 2004 and updated in 2013, which provided
detailed diagnostic criteria for AOM [1,2]
The educational campaign of the Centers for Disease Control and Prevention (CDC)
and other authoritative groups to influence parents and clinicians to avoid
inappropriate usage of antimicrobial agents for uncertain diagnoses of AOM [3]

The risk factors, microbiology, clinical features, and complications of AOM will be reviewed
here. Related topics are presented separately:

Acute otitis media in children: Diagnosis


Acute otitis media in children: Treatment
Acute otitis media in children: Prevention of recurrence
Otitis media with effusion (serous otitis media) in children: Clinical features and
diagnosis
Otitis media with effusion (serous otitis media) in children: Management
External otitis: Pathogenesis, clinical features, and diagnosis
Acute otitis media in adults (suppurative and serous)
Chronic otitis media, cholesteatoma, and mastoiditis in adults

DEFINITION AOM is defined by moderate to severe bulging of the tympanic membrane


(TM) or new onset of otorrhea not due to acute otitis externa accompanied by acute signs
of illness and signs or symptoms of middle ear inflammation [1]. Bulging of the TM (picture
1) is considered the quintessential sign that distinguishes AOM from otitis media with
effusion and a normal TM [4-7]. (See "Acute otitis media in children: Diagnosis", section on
'Acute otitis media'.)

EPIDEMIOLOGY AOM is the most frequent diagnosis in sick children visiting clinicians'
offices and the most common reason for administration of antibiotics [8-10]. AOM occurs at
all ages but is most prevalent between 6 and 24 months of age, after which it begins to
decline [11].

Incidence Nearly 80 percent of children in the United States <2 years of age have at
least one episode of AOM annually, and most continue to have episodes through age five
years [12-16]. AOM is slightly more common in boys than girls. An observational study that
reviewed claims data from a nationwide managed health care plan (2001 to 2011) found a
declining incidence of AOM following the introduction of the 13-valent pneumococcal
conjugate vaccine (PCV13), which accelerated beginning in 2009. In 2011, the incidence
of AOM was 0.82 episodes per child per year in children younger than two years [16].

Early onset AOM is the most important predictor of recurrent disease [11]. Children who
have had little or no experience with AOM by the age of three years are unlikely to have
subsequent severe or recurrent disease. AOM is infrequent in school-age children,
adolescents, and adults. (See "Acute otitis media in adults (suppurative and serous)",
section on 'Epidemiology of AOM'.)

Universal immunization of infants with the 7-valent pneumococcal conjugate vaccine


(PCV7) has decreased the incidence of AOM. In clinical trials, PCV7 reduced the overall
incidence of AOM by 6 to 7 percent (although there was a 34 percent decrease in
pneumococcal AOM) [17,18]. Postmarketing studies using medical claims from two states
found that office visits for otitis media decreased by 12 and 43 percent after the
introduction of PCV7 [19]. These studies used prevaccine and postvacccine claims data
and are not able to distinguish the effect of vaccine from secular changes, such as
changes in diagnostic criteria. The 13-valent pneumococcal vaccine replaced PCV7 in
2010. Review of claims data from a nationwide managed health care plan noted a decline
in episodes of AOM, children with recurrent otitis media, episodes of mastoiditis, and
tympanostomy tube insertion in children in 2011 compared with 2001 to 2009 [16].
(See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children", section
on '13-valent vaccine'.)

Risk factors A number of risk factors for AOM have been established, the most of
important of which is age.

Age The age-specific attack rate for AOM peaks between 6 and 18 months of age
[20]. After that, the incidence declines with age, although there is a small increase
between five to six years (the time of school entry). AOM is infrequent in school-age
children, adolescents, and adults. (See "Acute otitis media in adults (suppurative and
serous)", section on 'Epidemiology of AOM'.)
The occurrence of disease early in life is probably a result of a number of factors,
including immature anatomy, physiology, genetic predisposition, and immunologic
naivet. Some of these factors are identifiable (eg, the change in skull configuration
and vectors of the eustachian tube, development of antibodies following exposure to
bacterial pathogens), but others remain to be defined.
Family history Pooled analysis of three studies (1240 children) found that the risk
of AOM was increased if any other member of the family had history of AOM (relative
risk [RR] 2.63, 95% CI 1.86-3.72) [21].
The role of genetic factors in the development of AOM is suggested by a two-year
prospective study of same-sex twins and triplets [22]. The estimate of discordance for
an episode of AOM was greater among dizygotic than monozygotic twins (0.49 versus
0.04 percent). Potential pathogenetic mechanisms for the heritability of AOM include
anatomic, physiologic, and/or immunologic features. Polymorphisms in
proinflammatory cytokine genes and genes involved in innate and adaptive immunity
that increase susceptibility to otitis media and recurrent AOM have been identified
[23-26].
Day care The transmission of bacterial and viral pathogens is common in day care
centers. Multiple observational studies indicate that children attending day care
centers, especially with four or more other children, have a higher incidence of AOM
than children who receive care at home [14,27-29]. In pooled analysis of six studies
(1972 children), the RR of AOM for children who attended day care outside the home
compared with children who received care at home was 2.45 (95% CI 1.51-3.98) [21].
In pooled analysis of four studies (1030 children), the RR of AOM for children who
attended family day care versus home care was 1.59 (95% CI, 1.19-2.13) [21].
Lack of breastfeeding Lack of or limited breastfeeding is associated with an
increased risk of AOM [14,15,21,30,31]. In pooled analysis of six studies (2548
children), the risk of AOM was decreased among children who were breastfed for at
least three months (RR 0.87, 95% CI 0.79-0.95) [21].
Breastfeeding diminishes colonization of the nasopharynx by bacterial otopathogens
[21,30]. Additional reasons for the lower incidence of AOM among breastfed infants
are uncertain but may be related to immunologic or nonimmune protective factors in
breast milk, the facial musculature associated with breastfeeding, or the position
maintained during feeding from the breast contrasted with bottle feeding [32,33]. An
observational study suggests that the nasopharyngeal microbiome in breast fed
children is different from that in formula fed children, with a reduction in colonization
patterns with high densities of Streptococcus pneumoniae or
nontypeable Haemophilus influenzae [34]. (See "Infant benefits of breastfeeding",
section on 'Anti-microbial components'.)
Tobacco smoke and air pollution Exposure to tobacco smoke and ambient air
pollution increases the risk of AOM. In pooled analysis of three studies (1784
children), the RR of AOM was 1.66 (95% CI 1.33-2.06) among children whose
parents smoked [21]. In another pooled analysis, the odds ratio for recurrent AOM
was 1.48 (95% CI 1.08-2.04) if either parent smoked [35]. The mechanism for this
association is not entirely clear but may be related to increased nasopharyngeal and
oropharyngeal carriage of S. pneumoniae [36,37]. (See "Secondhand smoke
exposure: Effects in children", section on 'Middle ear disease'.)
Data are lacking regarding an association between ambient air pollution and middle
ear disease in children. Several observational studies have noted modest
associations between some air pollutants and otitis media in children, but the findings
are inconsistent [38-41]. Community-wide surveillance in a large city identified an
association between levels of sulfur dioxide (a marker for air pollution) and higher
ragweed pollen counts and invasive pneumococcal infections in children and adults
[42].
Pacifier use In pooled analysis of two studies (4110 children), children who used
a pacifier had a slightly higher incidence of AOM than children who did not (RR 1.24,
95% CI 1.06-1.46) [21].
Race and ethnicity Native Americans, Alaskan and Canadian Inuit children, and
indigenous Australian children have a higher incidence of severe and recurrent AOM
than do children of Caucasian descent [43,44]. In some indigenous populations, 40
percent of the children may have chronic perforation of the tympanic membrane by 18
months of age [45]. In a prospective study, severe otitis media was also more likely to
be reported in Bedouin than in Jewish children in Israel [46]; the authors attributed the
recurrent, nonresponsive, or chronic OM to crowded living conditions and colonization
early in life among Bedouin children, however, genetic differences were not
investigated. (See 'TM perforation' below.)
Developing areas Lack of access to medical care and local environmental factors
lead to severe suppurative episodes of OM in children living in developing areas [47].
The prevalence of chronic suppurative otitis media is discussed separately.
(See "Chronic suppurative otitis media (CSOM): Clinical features and diagnosis",
section on 'Epidemiology'.)
Other risk factors Other important risk factors in the development of single and
recurrent episodes of AOM include [20]:
Social and economic conditions (poverty and household crowding increase the
risk)
Season (increased incidence during the fall and winter months)
Altered host defenses and underlying disease (eg, cleft palate, Down syndrome,
allergic rhinitis)

PATHOGENESIS The middle ear is a narrow box that is part of an aerated system that
includes the nares, the eustachian tube, and the mastoid air cells (figure 1). The system is
lined with respiratory mucosa; events affecting one part of the system are usually reflected
in similar changes throughout the system. Extension of the suppurative process to
adjacent structures may lead to complications such as mastoiditis, labyrinthitis, petrositis,
meningitis, and lateral sinus thrombosis. (See 'Complications and sequelae' below.)

The pathogenesis of AOM in at-risk children generally involves the following sequence of
events [48-51]:

The patient has an antecedent event (usually a viral upper respiratory tract infection)
while colonized with an otopathogen(s) [15]. Some evidence suggest that co-
colonization with bacterial otopathogens only, in the absence of viral respiratory tract
infection, may be sufficient to trigger the cascade of events [50,52,53].
The event results in inflammatory edema of the respiratory mucosa of the nose,
nasopharynx, and eustachian tube.
Inflammatory edema obstructs the narrowest portion of the eustachian tube, the
isthmus.
Obstruction of the isthmus causes poor ventilation and resultant negative middle ear
pressure. This leads to the accumulation of secretions produced by the middle ear
mucosa.
The secretions have no egress and accumulate in the middle ear space.
Viruses and bacteria that colonize the upper respiratory tract enter the middle ear
via aspiration, reflux, or insufflation.
Microbial growth in the middle ear secretions often progresses to suppuration with
clinical signs of AOM (bulging tympanic membrane [TM], middle ear fluid,
erythematous TM).
The middle ear effusion may persist for weeks to months following sterilization of the
middle ear infection. (See "Acute otitis media in children: Treatment", section on
'Clinical course'.)

MICROBIOLOGY

Overview The microbiology of AOM has been documented by cultures of middle ear
effusion obtained by needle aspiration (table 1) [54]. Similar studies have been performed
to identify viral etiologies of AOM.

Bacterial and/or viral respiratory tract pathogens can be isolated from most middle ear
aspirates from children with AOM when a variety of microbiologic methods are used
[55,56]. In one series, bacteria (with or without viruses) were detected in 92 percent,
viruses (with or without bacteria) in 70 percent, and both bacteria and viruses in 66 percent
[55].

The finding of combined bacterial and viral infections in two-thirds of cases has important
clinical implications [57]. Mixed viral and bacterial infections may respond differently to
antibiotic therapy than purely bacterial infections [58,59]. The presence of viruses may
increase middle ear inflammation [60,61], decrease neutrophil function [62], and reduce
antibiotic penetration into the middle ear [63].

Bacteria Three species of bacteria account for most of the bacterial isolates from
middle ear fluid: S. pneumoniae, nontypeable H. influenzae (NTHi), and Moraxella
catarrhalis (table 1). This continues to be true even after the introduction of the conjugate
pneumococcal vaccines to the routine childhood immunization schedule [9,56,64-67].
However, the relative importance of the species has changed, and the pneumococcal
serotypes causing AOM have evolved to predominantly nonvaccine serotypes.

In prelicensure clinical trials, the 7-valent pneumococcal conjugate vaccine (PCV7)


reduced the incidence of pneumococcal AOM by 34 percent, although the overall
incidence of AOM declined by only 6 to 7 percent [17,18]. In the years immediately
following introduction of PCV7, two prospective studies, both in community-based pediatric
practices, noted significant declines in the proportion of S. pneumoniae isolates from
middle ear fluid (from approximately 45 to 30 percent) [64,68]. During the same time
frames, the proportion of NTHi isolates increased from approximately 40 to 55 percent
[64,68]. However, more recently, the proportion of S. pneumoniae and NTHi isolates is
reported to be nearly equivalent [66,69]. Such changes in proportion are distinct from
changes in incidence of disease.

Several studies have examined the microbiology and clinical features of bilateral versus
unilateral AOM [70,71]. Children with bilateral AOM were more likely to have bacteria
isolated from middle ear aspirate than children with unilateral AOM. H. influenzae was
isolated more often in children with bilateral than unilateral AOM, whereas S.
pneumoniae was isolated with equal frequency in children with bilateral and unilateral
AOM.

Following the introduction of PCV13, studies of tympanocentesis-confirmed AOM in


children in Israel and the United States demonstrated declines in overall episodes of AOM
and in episodes of AOM due to vaccine serotypes. Disease due to nonvaccine serotypes
and nonpneumococcal otopathogens (nonvaccine pneumococcal serotypes or NTHi) has
not yet increased [67,72].

S. pneumoniae S. pneumoniae accounts for approximately 50 percent of bacterial


isolates from the middle ear fluid of young children with severe, persistent, or refractory
AOM [66]. The proportion of pneumococcal isolates resistant to penicillin varies worldwide,
but resistance is more likely to be found in children with recurrent and/or persistent AOM
and in those recently exposed to antimicrobial agents [48,66]. S. pneumoniae is commonly
associated with first or early OM episodes [73,74], as well as with greater clinical severity
as reflected by high fever, more intense otalgia, and the potential for complications such as
bacteremia and mastoiditis [75]. Pneumococcal OM is also associated with a greater
inflammatory response with both elevated peripheral blood and middle ear fluid white
blood cell counts compared with other pathogens [73].

Widespread use of PCV7 has changed the S. pneumoniae serotypes responsible for AOM.
Before the introduction of PCV7 (table 2), serotypes included in the vaccine accounted for
60 to 70 percent of AOM isolates in the 6- to 59-month age group [76]. Following universal
immunization of infants with PCV7, most isolates recovered from the nasopharynx of
asymptomatic children and the middle ear of children with AOM are nonvaccine serotypes
[66,68,77-79]. Specifically, serotype 19A emerged as an important cause of both
respiratory tract infection and invasive disease. Of specific concern, multidrug-resistant
19A pneumococcus has been reported as the cause of recalcitrant AOM [77,79,80] and
coalescent mastoiditis [81]. PCV13, which was licensed in 2010, includes serotype 19A
(table 2). Surveillance after licensure of PCV13 has documented a decline in the
prevalence of nasopharyngeal colonization with serotypes unique to PCV13 including 19A
[82-84]. A decline in AOM episodes due to vaccine serotypes, including serotype 19A, has
also been reported in Israeli children referred for tympanocentesis following the
introduction of PCV13 [72]. Declines in AOM have also been seen in the first months of
life, suggesting herd benefit from decreased transmission of vaccine serotypes in the
community [85]. (See "Impact of universal infant immunization with pneumococcal
(Streptococcus pneumoniae) conjugate vaccines in the United States".)

H. influenzae H. influenzae accounts for approximately 45 percent of bacterial isolates


from the middle ear fluid of young children with severe, persistent, or refractory AOM
[9,66,79]. H. influenzae AOM is more often bilateral than unilateral [70,71,86]. OM caused
by NTHi is frequently associated with concurrent conjunctivitis and less severe symptoms
such as lower fever and a less inflamed tympanic membrane (TM) [71,73]. NTHi infection
is also associated with more complex OM, including increased risk for treatment failure,
recurrence despite appropriate antibiotic therapy, and chronicity [86]. Most H.
influenzae isolates from the middle ear are nontypeable [66]. Approximately one-third to
one-half of strains of H. influenzae recovered from middle ear fluids from children in the
United States produce beta-lactamase [48,65,87]. (See "Microbiology, epidemiology and
treatment of Haemophilus influenzae", section on 'Nontypeable H. influenzae'.)

Universal immunization of infants with the conjugate H. influenzae type b vaccine has had
little effect on Haemophilus AOM because more than 90 percent of Haemophilus AOM is
caused by nontypeable strains. However, studies of the microbiology of AOM after the
introduction of the pneumococcal conjugate vaccine suggest the proportion of cases due
to H. influenzae is increasing. It is unclear how the incidence of disease due to NTHi has
changed. Some studies suggest an increase in incidence following introduction of
pneumococcal conjugate vaccines, while others suggest declines in NTHi AOM in early
episodes but increased incidence in recurrent disease [9,17,66,68,85,88].

M. catarrhalis M. catarrhalis accounts for approximately 10 percent of bacterial middle


ear isolates in children with AOM in the United States [87], a percentage that has been
little affected by universal immunization of infants with pneumococcal conjugate vaccine
[9,68]. More than 90 percent of strains produce beta-lactamase [68,87].

Group A Streptococcus Group A Streptococcus occasionally causes AOM (2 to 10


percent of isolates) [9]. Group A streptococcal AOM tends to occur in older children and to
be more frequently associated with local complications (eg, TM perforation, mastoiditis)
and less frequently associated with fever and systemic or respiratory symptoms than AOM
caused by other organisms [89,90].

Staphylococcus aureus Staphylococcus aureus is an uncommon cause of AOM, but its


prevalence appears to have increased after licensure of PCV7 [9,88,91,92]. It is found
often as a cause of acute otorrhea in children with tympanostomy tubes in place.

Other bacteria Anaerobic bacteria infrequently cause AOM. Enteric gram-negative


bacilli such as Escherichia coli may cause AOM in the first months of life
[93,94]. Pseudomonas aeruginosa has a special role in chronic suppurative otitis media.
(See "Pseudomonas aeruginosa infections of the eye, ear, urinary tract, gastrointestinal
tract, and central nervous system", section on 'Ear infections'.)
Viruses Microbiologic and epidemiologic data suggest that viral infection is frequently
associated with AOM [55,95-98]. With advances in microbiologic techniques, including
reverse transcriptase PCR, viruses are increasingly detected in the middle ear fluid of
children with AOM [55,97]. The most frequently isolated viruses are respiratory syncytial
virus (RSV), picornaviruses (eg, rhinovirus, enterovirus), coronaviruses, influenza viruses,
adenoviruses, and human metapneumovirus. However, in an epidemiologic study, only
influenza, RSV, and human metapneumovirus activity in the community were associated
with an increase in AOM diagnoses [99]. (See appropriate topic reviews.)

Other pathogens Mycoplasma pneumoniae rarely has been isolated from middle ear
fluids of children with AOM. Chlamydia trachomatis has been associated with otitis media
in infants younger than six months of age. C. pneumoniae has been isolated from some
patients with acute and chronic otitis media [54]. (See "Chlamydia trachomatis infections in
the newborn" and "Mycoplasma pneumoniae infection in children", section on 'Clinical
features'.)

In young infants The microbiology of AOM in infants younger than two months has
been evaluated in several observational studies, the most recent of which is from the
1990s [93,94,100-106]. Bacterial pathogens isolated from the middle ear aspirates of
young infants with AOM most commonly are similar to those identified in older children
(eg, S. pneumoniae and H. influenzae). In infants younger than two weeks, pathogens that
cause neonatal sepsis (group B Streptococcus, enteric gram-negative bacilli, and S.
aureus) also may be found.

Developing countries In developing countries, the most common bacterial causes of


AOM are the same as in developed countries [107-109]. AOM due to both H.
influenzae and S. pneumoniae, in combination, is observed more frequently in certain
populations [46]. In addition, OM may be caused by Mycobacteria
tuberculosis, Corynebacterium diphtheriae, and Clostridium tetani. Parasitic (Ascaris
lumbricoides) and fungal (Blastomyces dermatitidis, Candida and Aspergillus species)
middle ear infections may occur but are rare [107].

CLINICAL MANIFESTATIONS

Symptoms and signs Children with AOM, particularly infants, may present with
nonspecific symptoms and signs, including fever, irritability, headache, apathy, disturbed or
restless sleep, poor feeding/anorexia, vomiting, and diarrhea [110-114]. Fever occurs in
one- to two-thirds of children with AOM, though temperature >40C (104F) is unusual
unless accompanied by bacteremia or other focus of infection [115]. The lack of specificity
of symptoms of AOM in young children, particularly in infants, makes the diagnosis
challenging. (See "Acute otitis media in children: Diagnosis", section on 'Diagnosis'.)

Ear pain (otalgia) is the most common complaint in children with AOM and the best
predictor of AOM [110,111,113]. However, ear pain and other ear-related symptoms (eg,
ear rubbing) are not always present [110,111,116]. In a prospective study of 335
consecutive episodes of AOM, otalgia was severe in 42 percent, mild to moderate in 40
percent, and absent in 17 percent [116]. Children older than two years complained of ear
pain more often than children younger than two years (25 versus 7 percent) [116]. Other
causes of ear pain in children are discussed separately. (See "Evaluation of earache in
children".)

The most important sign for distinguishing AOM from OM with effusion and normal is the
presence of bulging of the tympanic membrane (TM) (picture 1) [4-6]. Other signs and
symptoms of AOM include otorrhea and hearing loss. Findings that may be associated
with complications of AOM include vertigo, nystagmus, tinnitus, swelling about the ear, and
facial paralysis [113]. (See 'Complications and sequelae' below.)

Clinical syndromes

Otitis-conjunctivitis The symptom complex of otitis media and purulent conjunctivitis


is called otitis-conjunctivitis (conjunctivitis-otitis) syndrome [117-120]. In a series of 124
patients with otitis-conjunctivitis, 50 percent were younger than two years [119]. The ear
pain typically began on the same day as, or within three days after, the ophthalmologic
symptoms. Otitis-conjunctivitis is usually caused by NTHi, although it can be caused by
other organisms [120,121].

Bullous myringitis Bullous myringitis is inflammation of the TM that occurs in


association with AOM in which bullae are present on the TM (picture 2A-B). Bullous
myringitis occurs in approximately 5 percent of cases of AOM in children younger than two
years [122]. Children with bullous myringitis usually have more pain at the time of
diagnosis than children without bullous myringitis [76]. The distribution of viral and bacterial
pathogens in cases of bullous myringitis is similar to that in cases of AOM without bullae
[123-128]. The treatment and prognosis for bullous myringitis are the same as for AOM
without bullae. (See "Acute otitis media in children: Treatment".)

DIAGNOSIS The diagnosis of AOM requires [1,7]:

Signs and symptoms of middle ear inflammation (eg, bulging of the tympanic
membrane [TM], distinct erythema of the TM or otalgia, fever) (picture 1), and
Middle ear effusion (eg, TM opacity, decreased or absent TM mobility (movie 1), an
air-fluid level, or otorrhea)

Thus, a diagnosis of AOM can be made in a child with moderate to severe bulging of the
TM; new onset of otorrhea not due to acute otitis externa; or mild bulging of the TM and
recent onset (<48 hours) of ear pain or intense erythema of the TM (picture 3) [1].

The diagnosis of AOM is discussed separately. (See "Acute otitis media in children:
Diagnosis".)
Clues to etiology Despite the lack of specificity of most ear-related findings in the
diagnosis of AOM, some clinical features correlate with particular organisms.

Eye findings, particularly conjunctivitis, are more common with H. influenzae [73]
(see 'Otitis-conjunctivitis' above)
H. influenzae is isolated more often from children with bilateral than unilateral AOM,
whereas S. pneumoniae is isolated with equal frequency in bilateral and unilateral
AOM [70,71]
Although spontaneous TM perforation can occur in all types of bacterial AOM, AOM
caused by group A streptococci (GAS) is associated with higher rates of TM
perforation than AOM caused by other pathogens [89,90]
AOM caused by S. pneumoniae is more likely to present with severe symptoms
(high fever and moderate to severe pain) [73,75].

Dual pathogen infection AOM due to both S. pneumoniae and nontypeable H.


influenzae has received increasing attention as part of the spectrum of middle ear disease.
Mixed infection, most commonly S. pneumoniae and H. influenzae, has been identified in
children with persistent AOM and/or recurrent OM from multiple countries [129-131]. The
persistence and recurrence of these polymicrobial OM infections likely reflects biofilms in
the middle ear space and is more likely in children with recurrent disease.

COMPLICATIONS AND SEQUELAE

Intratemporal complications Intratemporal (extracranial) complications of AOM


include [132,133]:

Hearing loss (secondary to middle ear fluid, ossicular fixation or disruption, or


involvement of the eighth cranial nerve)
Balance and motor problems
Tympanic membrane (TM) perforation, tympanosclerosis (asymptomatic whitish
plaques) (picture 4)
Middle ear atelectasis (retraction or collapse of the TM due to chronic or recurrent
decreased pressure in the middle ear) (picture 5)
Cholesteatoma (picture 6)
Ossicular fixation or discontinuity secondary to proliferation of fibrous tissue in the
mucous membranes ("adhesive otitis media")
Extension of the suppurative process to adjacent structures (mastoiditis, petrositis,
labyrinthitis)

Hearing loss Most patients with middle ear effusion have persistent or fluctuating
conductive hearing loss. Fluid filling the middle ear space prevents the TM from vibrating
adequately, thereby diminishing movement of the ossicular chain. The hearing loss
remains as long as fluid fills the middle ear space. The median loss is 25 dB, which is
equivalent to putting plugs in the child's ears. (See "Hearing impairment in children:
Etiology", section on 'Infection'.)

Despite treatment with appropriate antimicrobial agents, middle ear fluid may persist for
weeks to months after the onset of signs of AOM (see "Acute otitis media in children:
Treatment", section on 'Clinical course'). Some studies have noted that children with
prolonged time spent with middle ear effusion have lower scores on tests of speech,
language, and cognitive abilities than children without prolonged middle ear effusion [134-
137]. Other studies found no significant differences in developmental outcome between
children with and without prolonged middle ear effusion [138-142]. Systematic reviews and
meta-analyses have found either inconclusive evidence or small to no negative effects of
prolonged middle ear effusion on speech and language development [143-145]. However,
the findings may not be generalizable to children at increased risk of speech and language
delay (eg, those with craniofacial anomalies, pre-existing developmental delays, persistent
bilateral OM, etc).

Sensorineural hearing loss is an uncommon consequence of AOM but may occur.

Balance and motor problems Children with AOM may have balance, motor, or
vestibular problems related to vestibular dysfunction or labyrinthitis [133,146-149].
(See "Pathophysiology, etiology, and differential diagnosis of vertigo", section on 'Otitis
media'.)

TM perforation The increased pressure in the middle ear can result in central
ischemia, necrosis, and spontaneous perforation of the TM, usually accompanied by
otorrhea (picture 7) [132].

The frequency of spontaneous perforation is increased in Native Americans, Australian


Aborigines, and in children in developing countries [43]. AOM caused by group A
streptococci (GAS) is associated with higher rates of TM perforation than AOM caused by
other pathogens [89,90]. The risk of perforation is also increased in children initially
observed without antimicrobial therapy [150,151].

The treatment of TM perforation associated with AOM is discussed separately. (See "Acute
otitis media in children: Treatment", section on 'AOM with perforation'.)

Chronic suppurative otitis media Unresolved or complicated AOM with perforation of


the TM may lead to chronic suppurative otitis media (CSOM) or chronic otomastoiditis,
which is defined as the presence of perforation of the TM with chronic purulent drainage
from the middle ear cleft for more than six weeks (picture 8). Most often CSOM is the end
stage of recurrent AOM episodes that begin in the first year of life. (See "Chronic
suppurative otitis media (CSOM): Clinical features and diagnosis".)

Children with TM perforation and suppurative discharge that persists despite


oral and/or topical antibiotics should be referred to an infectious disease specialist or
otolaryngologist as soon as possible. Children with perforation without drainage that
persists for three months or longer should be referred to an otolaryngologist for further
management [132]. Prevention of CSOM entails prompt and appropriate treatment of
acute middle ear infection [43]. Chemoprophylaxis is not warranted. (See "Chronic
suppurative otitis media (CSOM): Treatment, complications, and prevention".)

Cholesteatoma A cholesteatoma is an abnormal growth of squamous epithelium in the


middle ear and mastoid that may progressively enlarge to surround and destroy the
ossicles. Recurrent AOM, which may lead to retraction pockets in the TM, is a risk factor
for cholesteatoma.

Clinical features suggestive of acquired cholesteatomas include deep retraction pockets,


as in panel A (picture 9), a white mass behind the TM (picture 6), focal granulation at the
periphery of the TM (picture 10), new-onset hearing loss, and ear drainage for more than
two weeks despite treatment. The diagnosis and management of cholesteatoma are
discussed separately. (See "Cholesteatoma in children", section on 'Clinical
features' and "Cholesteatoma in children", section on 'Surgical treatment'.)

Mastoiditis Because the mastoid air cells are connected to the distal end of the middle
ear through a small canal or antrum (figure 2), most episodes of AOM are associated with
some inflammation of the mastoid. In rare cases, resolution of the mastoid infection does
not occur, and acute mastoiditis develops with pus filling the air cells. (See "Acute
mastoiditis in children: Clinical features and diagnosis", section on 'Pathogenesis'.)

The epidemiology of mastoiditis in children is discussed separately. (See "Acute


mastoiditis in children: Clinical features and diagnosis", section on 'Epidemiology'.)

Other intratemporal complications Other intratemporal complications of AOM include


[133]:

Petrositis (extension of the infection into the petrous portion of the mastoid bone)
(see "Acute mastoiditis in children: Clinical features and diagnosis", section on
'Complications')
Labyrinthitis (extension of infection into the cochlear and vestibular apparatus)
(see "Pathophysiology, etiology, and differential diagnosis of vertigo", section on 'Otitis
media')
Facial paralysis (the facial nerve courses through the middle ear and mastoid); facial
paralysis also may occur as a complication of acute mastoiditis or chronic suppurative
otitis media (see "Facial nerve palsy in children", section on 'Otitis media')

Intracranial complications Intracranial complications of AOM are uncommon in


developed countries. However, they remain a concern in developing countries where
access to medical care is limited [107,152]. Intracranial complications of AOM include:
Meningitis (see "Bacterial meningitis in children older than one month: Clinical
features and diagnosis", section on 'Clinical features')
Epidural abscess (see "Intracranial epidural abscess", section on 'Clinical
manifestations')
Brain abscess (see "Pathogenesis, clinical manifestations, and diagnosis of brain
abscess", section on 'Clinical manifestations')
Lateral sinus thrombosis (see "Septic dural sinus thrombosis", section on 'Septic
lateral sinus thrombosis')
Cavernous sinus thrombosis (see "Septic dural sinus thrombosis", section on 'Septic
cavernous sinus thrombosis')
Subdural empyema (collection of purulent material between the dura and the
arachnoid membrane)
Carotid artery thrombosis

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Ear infections (otitis media) (The Basics)")
Beyond the Basics topics (see "Patient education: Ear infections (otitis media) in
children (Beyond the Basics)")

SUMMARY

Acute otitis media (AOM) is defined by the presence of fluid in the middle ear
accompanied by acute signs of illness and signs or symptoms of middle ear
inflammation, including bulging (picture 1). (See 'Introduction' above
and 'Definition' above.)
Viral upper respiratory infection is the most common predisposing factor for the
development of AOM. The incidence of AOM in the United States is highest between
6 and 18 months of age and during the respiratory virus season. In addition to young
age, other risk factors for AOM include family history, day care attendance, not having
been breastfed, exposure to tobacco smoke, pacifier use, and ethnicity (Native
Americans and Alaskan and Canadian Inuit populations). (See 'Risk factors' above.)
Inflammation of the upper respiratory tract predisposes to AOM via dysfunction of
the eustachian tube, leading to negative pressure and accumulation of middle ear
secretions and impairment in host defenses such as normal mucociliary action of the
respiratory mucosa. Microbial growth in the middle ear secretions may result in
suppuration and clinical signs of AOM. (See 'Pathogenesis' above.)
Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi),
and Moraxella catarrhalis account for most of the bacterial isolates from middle ear
fluid. The most common viral pathogens include respiratory syncytial virus,
rhinoviruses, influenza viruses, and adenoviruses. (See 'Microbiology' above.)
Children with AOM, particularly infants, may present with nonspecific symptoms and
signs (eg, fever, fussiness, headache, anorexia, vomiting, and diarrhea). Specific
findings of AOM or complications/sequelae of AOM include ear pain, otorrhea, bulging
of the tympanic membrane (TM) (picture 1), hearing loss, vertigo, nystagmus, tinnitus,
swelling about the ear, and facial paralysis. (See 'Symptoms and signs' above.)
AOM may occur in conjunction with conjunctivitis; this symptom complex is usually
caused by NTHi. AOM also may occur with bullae on the TM (bullous myringitis
(picture 2A)); the distribution of viral and bacterial pathogens in cases of bullous
myringitis is similar to that in cases of AOM without bullae. (See 'Clinical
syndromes' above.)
The diagnosis of AOM requires evidence of middle ear inflammation (eg, bulging)
and middle ear effusion. (See "Acute otitis media in children: Diagnosis", section on
'Diagnosis'.)
Complications of AOM include mild conductive hearing loss; vestibular, balance, and
motor dysfunctions; TM perforation; inflammation of the mastoid and/or mastoiditis;
petrositis; and labyrinthitis. Intracranial complications are rare in developed countries;
they include meningitis, epidural abscess, brain abscess, lateral sinus thrombosis,
cavernous sinus thrombosis, subdural empyema, and carotid artery thrombosis.
(See 'Complications and sequelae' above.)

Acute otitis media in children: Diagnosis

Author:
Ellen R Wald, MD
Section Editors:
Morven S Edwards, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 27, 2016.
INTRODUCTION Acute otitis media (AOM), also called suppurative otitis media, is one
of the most frequent diagnoses for children seeking acute medical care [1]. It accounts for
a large proportion of pediatric antibiotic prescriptions and is associated with considerable
medical expenditures [2,3].

The diagnosis of AOM will be reviewed here. The epidemiology, pathogenesis, treatment,
and prevention of AOM are discussed separately. (See "Acute otitis media in children:
Epidemiology, microbiology, clinical manifestations, and complications" and "Acute otitis
media in children: Treatment" and "Acute otitis media in children: Prevention of
recurrence".)

TERMINOLOGY

Middle ear effusion Middle ear effusion (MEE) refers to fluid in the middle ear cavity.
MEE occurs in both otitis media with effusion and AOM.

Acute otitis media AOM refers to acute infection of middle ear fluid. (See "Acute otitis
media in children: Epidemiology, microbiology, clinical manifestations, and complications",
section on 'Definition'.)

Otitis media with effusion Otitis media with effusion (OME) refers to middle ear fluid
that is not infected. OME is also called serous, secretory, or nonsuppurative otitis media.
OME frequently precedes the development of AOM or follows its resolution. (See "Otitis
media with effusion (serous otitis media) in children: Clinical features and diagnosis",
section on 'Clinical features'.)

The distinction between OME and AOM may be difficult, since they are part of a
continuous spectrum. (See "Acute otitis media in children: Treatment", section on 'Clinical
course' and 'Otitis media with effusion' below.)

ANATOMY The anatomic features of the right tympanic membrane are depicted in the
figure (figure 1). The normal middle ear is aerated, and the tympanic membrane is slightly
convex, translucent, mobile, and intact (picture 1). In contrast, in established AOM, the
middle ear is fluid-filled, and the tympanic membrane is usually bulging, yellow or white in
color, opaque, and immobile (picture 2). In some cases, the tympanic membrane may be
erythematous, but erythema of the tympanic membrane is a nonspecific finding; it is only
helpful in making a diagnosis of AOM if there is concomitant bulging. Increased pressure in
the middle ear may lead to central ischemia, necrosis, and perforation of the tympanic
membrane.

IMPORTANCE OF ACCURATE DIAGNOSIS The importance of accurate diagnosis of


AOM cannot be overstated. Accurate diagnosis ensures appropriate treatment for children
with AOM, who require antibiotic therapy, and avoidance of antibiotics in children with otitis
media with effusion, in whom antibiotics are unnecessary. Accurate diagnosis also
prevents overuse of antibiotics, which leads to the development of resistant organisms [4-
6]. (See "Otitis media with effusion (serous otitis media) in children: Management", section
on 'Overview of management' and "Acute otitis media in children: Treatment", section on
'Antibiotic therapy versus observation'.)

Establishing the diagnosis of AOM in infants and young children can be difficult. The child
may not cooperate with the examination, and the tympanic membrane may be obscured
by cerumen. In addition, symptoms of AOM may overlap with those of upper respiratory
tract infection or may be subtle or absent [7-11]. (See "Acute otitis media in children:
Epidemiology, microbiology, clinical manifestations, and complications", section on
'Symptoms and signs'.)

OTOSCOPY The diagnosis of AOM is facilitated by systematic assessment of the


tympanic membrane using a pneumatic otoscope and stringent diagnostic criteria to
distinguish AOM from otitis media with effusion (OME). Otoscopy is performed using
appropriate tools and an adequate light source (eg, a halogen bulb with brightness 100
foot-candles [1000 lux]) [12]. The otoscope bulb should be replaced at least every two
years, and the battery replaced when outdated [12]. Pneumatic otoscopy skills, including
accurate interpretation of findings, can be improved through training [13,14]. Excellent
training modules are available online (eg, Children's Hospital of Pittsburgh ePROM:
Enhancing Proficiency in Otitis Media).

A pneumatic otoscope with a round head is preferred because it has the best seal (picture
3). The magnifying glass can be moved aside if and when cerumen removal is necessary.
The nipple on the metal head is the site of attachment for the insufflator bulb, which is
used to assess mobility of the tympanic membrane. (See 'Mobility' below.)

Cerumen must be removed from the external canal under direct vision in order to be sure
that the view of the tympanic membrane is unobstructed. Once cerumen has been
removed, systematic assessment of the entire tympanic membrane is undertaken, as
described below. (See "Cerumen", section on 'Cerumen removal'.)

Overview The diagnosis of AOM requires middle ear effusion (MEE) and acute signs of
middle ear inflammation (bulging of the tympanic membrane is the most specific and
reproducible sign of middle ear inflammation) [15,16]. The classic examination findings
include a tympanic membrane that is white or pale yellow, bulges into the external auditory
canal, and has decreased or absent mobility (picture 4) [17-19]. However, this constellation
of findings is not always present. (See 'Diagnosis' below.)

Accurate diagnosis of AOM requires systematic evaluation of the tympanic membrane for
position, translucency, mobility, color, and other findings (eg, fluid level, perforation).
Systematic assessment of the tympanic membrane is facilitated by the use of the
COMPLETES mnemonic [20]:

Color (eg, gray, white, pale yellow, amber, pink, red, blue)
Other conditions (eg, fluid level, bubbles, perforation, otorrhea, bullae,
tympanosclerosis [scars], atrophic areas, retraction pockets, cholesteatoma)
Mobility
Position (eg, neutral, retracted, full, or bulging)
Lighting (a halogen light source and fully charged battery should be used)
Entire surface (the four quadrants of the tympanic membrane should be examined)
(figure 1)
Translucency
External auditory canal and auricle (eg, deformed, displaced, inflamed, foreign body)
Seal (a good seal requires an airtight pneumatic system and a speculum that is
large enough to prevent air leak)

Although the COMPLETES mnemonic serves as a reminder of the important aspects of


the otoscopic examination, it reflects neither the order of the examination nor the
importance of the individual components in distinguishing AOM from OME [20].

Experienced otoscopists at a tertiary care children's hospital developed and validated a


classification scheme describing the signs and symptoms that they use to diagnose AOM
[15]:

Bulging tympanic membrane (with or without opacification or air-fluid level): AOM


Opacification of the tympanic membrane or air-fluid level: OME
Absence of bulging, opacification, and air-fluid level: no MEE

Although the cases of AOM, OME, and no MEEs that were used to develop and validate
the classification scheme were not microbiologically confirmed, the otoscopists had
completed a training program in which their diagnoses were validated against
myringotomy findings. Expert otoscopists from other centers concurred in the relative
importance of the findings of otoscopy [19]. We agree that bulging of the tympanic
membrane is the crucial finding that differentiates AOM from OME.
(See 'Diagnosis' below.)

Position A bulging tympanic membrane is the hallmark of AOM [10,15,17,19]. The


position of the tympanic membrane is the most critical characteristic in distinguishing AOM
from OME [10,15,17,19]. Position may be described as neutral, retracted, full, or bulging.

The normal position of the tympanic membrane is neutral (picture 1).


When there is negative pressure in the middle ear cavity, as may occur in persistent
OME, the tympanic membrane is retracted (picture 5). When the tympanic membrane
is retracted, the manubrium of the malleus appears to be shortened, and the lateral
process becomes more prominent and seems closer to the otoscope [20,21].
When there is infected fluid in the middle ear, the tympanic membrane may appear
to be full; larger amounts of infected fluid make it appear to bulge. Bulging is first
apparent in the posterosuperior area, where the tympanic membrane is most
compliant (figure 1). When the tympanic membrane is bulging, the malleus handle is
obscured (picture 4) [21].

A bulging tympanic membrane is the single most important sign of acute inflammation
[10,15,17,19]. In a large study correlating examination findings with a diagnosis of AOM,
the triad of bulging tympanic membrane, impaired mobility, and redness or cloudiness of
the tympanic membrane predicted myringotomy diagnosis of AOM in 83 to 99 percent of
cases [17]. In another study correlating examination findings with a diagnosis of AOM, 92
percent of children with AOM had a bulging tympanic membrane compared with none of
the children with OME or no effusion [15]. In a systematic review, the adjusted likelihood
ratio (LR) for bulging tympanic membrane was 51 (95% CI 36-73) [10].

In a large study correlating examination findings with a diagnosis of AOM, retracted


tympanic membranes were unlikely to be associated with AOM [17]. Normally positioned
tympanic membranes were unlikely to be associated with AOM unless mobility was
distinctly impaired.

Translucency Translucency of the tympanic membrane is another important aspect of


the examination. The tympanic membrane normally appears translucent (picture 1). In
contrast, the tympanic membrane appears cloudy or opaque when there is fluid in the
middle ear. Opacification of the tympanic membrane is not helpful in differentiating AOM
from OME. In a study correlating examination findings with a diagnosis of AOM by
experienced otoscopists, opacity of the tympanic membrane was present in 50 of 50 cases
of AOM and 33 of 34 cases of OME [15].

An air-fluid level is present when the tympanic membrane appears translucent above and
opaque below the line of demarcation (picture 6). Air fluid levels are more suggestive of
OME than AOM [15]. Air-fluid levels fluctuate with pneumatic otoscopy, a technique that
helps distinguish fluid levels from tympanosclerosis, which, being part of the tympanic
membrane, moves with it. (See 'Mobility' below.)

Mobility Pneumatic assessment of the mobility of the tympanic membrane is an


important means of determining the presence of MEE, an essential criterion for AOM
[20,22,23]. However, pneumatic assessment does not indicate whether the fluid is infected
and cannot be used in isolation to make a diagnosis of AOM.

Bulging of the tympanic membrane remains the single most important sign of AOM and
precludes the necessity of pneumatic otoscopy because all bulging membranes have
decreased or absent mobility. In addition, pneumatic otoscopy can be extremely painful in
children with AOM.

Procedure Mobility of the tympanic membrane is assessed by creating positive and


negative pressures within the external auditory canal by using the insufflator bulb of the
otoscope. A good seal between the speculum and the external auditory canal is essential
in order to make a judgment regarding mobility. A seal cannot be obtained if the tympanic
membrane is perforated or contains a patent tympanostomy tube, or if the speculum is too
small.

To ensure an airtight seal, the largest speculum that fits comfortably into the cartilaginous
portion of the external auditory canal should be used (a 4 mm speculum will work for most
children) [20]. The outer diameter of the speculum may be increased by putting a small
piece of rubber tubing around the tip of the speculum [21,24].

A leak in the pneumatic system is another reason for a poor seal. The pneumatic system
should be checked for leaks periodically by occluding the tip of the speculum with a finger
and squeezing the rubber bulb to see if resistance is felt [20].

Mobility of the tympanic membrane is best visualized in the posterosuperior quadrant or


pars flaccida, where the tympanic membrane is most compliant (figure 1). Positive
pressure is created when the insufflator bulb is compressed, and negative pressure when
it is released. The tympanic membrane moves away from the observer with positive
pressure and toward the observer with negative pressure (movie 1).

When there is high negative pressure in the middle ear cavity, the tympanic membrane
may be maximally retracted and unable to move away from the observer with positive
pressure (movie 2). Mobility of a retracted tympanic membrane can be assessed by
creating negative pressure in the external auditory canal. The otoscope should be
removed from the external canal and the bulb compressed. After the bulb is compressed,
the otoscope is reinserted into the external canal. When the seal is secured, the bulb is
released, creating negative pressure, which allows the retracted tympanic membrane to
move toward the observer into a neutral position.

Interpretation Mobility is described as normal (movie 1), increased, absent (movie 2),
or decreased.

Increased mobility of an area of the tympanic membrane may be caused by atrophy


(an atrophied tympanic membrane is referred to as "dimeric"). The site of a previous
perforation or tympanostomy tube also may have increased mobility.
Absent or decreased mobility of the tympanic membrane may be caused by MEE
(infected or uninfected) or scarring of the tympanic membrane (tympanosclerosis or
myringosclerosis) (picture 7). (See 'Other findings' below.)

The finding of decreased or absent mobility of the tympanic membrane can confirm a
diagnosis of MEE. When using this criterion to establish MEE, it is essential that the
adequacy of the seal be assured; if it is not, the diagnosis of MEE may be faulty.
Decreased or absent mobility should not be used as the sole criterion for AOM since it
provides no information regarding whether the fluid is infected or uninfected.
(See 'Diagnosis' below.)
In a study correlating examination findings with a diagnosis of AOM by experienced
otoscopists, decreased mobility of the tympanic membrane was present in 50 of 50 cases
of AOM and 23 of 34 cases of OME [15].

Color Assessment of the color of the tympanic membrane is another important aspect
of the otoscopic examination.

Under normal conditions, the color of the tympanic membrane is pearly gray or pink
(picture 1).
When there is uninfected fluid in the middle ear (ie, OME), the color is usually
amber, gray, or blue.
A white or pale yellow tympanic membrane usually indicates pus in the middle ear
cavity, which is a sign of AOM (picture 4).
Asymptomatic whitish plaques of calcium and phosphate crystals that move with the
tympanic membrane are known as tympanosclerosis or myringosclerosis (picture 7).
(See 'Other findings' below.)
A red or hemorrhagic-appearing tympanic membrane may indicate acute
inflammation, but a hyperemic tympanic membrane also may be caused by
vasodilatation related to manipulation of the canal (as occurs during removal of
cerumen), crying, or high fever. In the crying child, vascular engorgement is limited to
the periphery and handle of the malleus [25]. Vessels crossing the tympanic
membrane suggest inflammation.

The finding of an erythematous tympanic membrane is less important in the diagnosis of


AOM than assessment of the position and mobility [10,15,17]. In a large study correlating
otoscopic findings and AOM, a distinctly red tympanic membrane (defined as hemorrhagic,
strongly, or moderately red) in the absence of bulging or impaired mobility predicted a
diagnosis of AOM in only 15 percent of cases [17]. In a systematic review, the adjusted LR
for a distinctly red TM was 8.4 (95% CI 6.7-11) and for a slightly red tympanic membrane
was 1.4 (95% CI 1.1-1.8) [10].

Other findings In addition to position, translucency, mobility, and color, the tympanic
membrane should be assessed for the following other findings [20]:

Bubbles or fluid levels (picture 6), which indicate MEE. (See 'Translucency' above.)
Acute perforation with purulent otorrhea, which satisfies the criteria for diagnosis of
AOM provided that otitis externa is excluded. (See "External otitis: Pathogenesis,
clinical features, and diagnosis".)
Bullae, which are caused by inflammation of the tympanic membrane that occurs in
association with AOM (picture 8). (See "Acute otitis media in children: Epidemiology,
microbiology, clinical manifestations, and complications", section on 'Bullous
myringitis'.)
Tympanosclerosis of the tympanic membrane (asymptomatic whitish plaques of
calcium and phosphate crystals) (picture 7), which may be the result of chronic middle
ear inflammation, perforation, myringotomy with or without tympanostomy tube
placement, or trauma. Tympanosclerosis moves with the tympanic membrane during
otoscopy. (See "Otitis media with effusion (serous otitis media) in children: Clinical
features and diagnosis", section on 'Complications and sequelae'.)
Atrophic areas, which may be the sequelae of otitis media or its treatment; atrophic
areas may have increased mobility. (See 'Mobility' above.)
Retraction pockets (picture 9), which may be sequelae of otitis media. Retraction
pockets can predispose to the development of cholesteatoma (a benign growth of
desquamated, stratified, squamous epithelium). A cholesteatoma may appear as a
cyst within the tympanic membrane, greasy white debris, or as a mass (picture 10). If
not treated, the cholesteatoma may gradually enlarge, with eventual erosion of the
ossicular chain, mastoid air cells, and external auditory canal. Patients with
cholesteatoma or suspected cholesteatoma should be referred to an otolaryngologist.
(See "Cholesteatoma in children".)
The light reflex is a cone of light in the anterior inferior portion of the tympanic
membrane that may be seen during otoscopy. Neither its presence nor absence is a
helpful sign in distinguishing AOM from OME. When present, the light reflex can be
observed for change during the assessment of mobility.

TYMPANOMETRY AND ACOUSTIC REFLECTOMETRY Tympanometry and acoustic


reflectometry are techniques to predict the presence or absence of middle ear effusion
(MEE). Neither technique provides information regarding whether the fluid is infected or
uninfected [26,27]. If tympanometry and/or acoustic reflectometry are normal, acute otitis
media is unlikely.

DIAGNOSIS

Clinical diagnosis The clinical diagnosis of AOM requires [15]:

Bulging of the tympanic membrane, or


Very infrequently, other signs of acute inflammation and middle ear effusion (MEE)

A diagnosis of AOM also can be established if there is acute purulent otorrhea and otitis
externa has been excluded [22]. (See "External otitis: Pathogenesis, clinical features, and
diagnosis", section on 'Diagnosis'.)

Bulging of the tympanic membrane The best and most reproducible sign of
acute inflammation is distinct fullness or bulging of the tympanic membrane (picture
4) [10,15,17,19]. Experienced otoscopists rarely make the diagnosis of AOM in the
absence of bulging of the tympanic membrane [15,19]. (See 'Position' above.)
Other signs of inflammation Signs of acute inflammation are necessary to
differentiate AOM from otitis media with effusion (OME). Marked redness of the
tympanic membrane is another sign of acute inflammation [22]. However, marked
redness of the tympanic membrane without bulging is unusual in AOM [15]. A
distinctly red tympanic membrane in the absence of bulging or impaired mobility has a
positive predictive value of only 15 percent for AOM [17].
Nonotoscopic signs and symptoms such as fever, ear tugging, or otalgia must be
accompanied by abnormal otoscopic findings to make a diagnosis of AOM. As an
example, a child who complains of ear pain may be diagnosed with AOM when he or
she also has a bulging tympanic membrane.
MEE MEE can be confirmed by one or both of the following findings on otoscopy
[22]:
Bubbles or an air-fluid level (picture 6)
Two or more of the following:
-Abnormal color (white, yellow, amber, or blue)
-Opacity (involving part or all of the tympanic membrane) not due to
scarring
-Impairment of mobility (movie 2)
MEE also can be confirmed by myringotomy/tympanocentesis, but this procedure is
rarely performed in the primary care setting [5,10].
MEE is necessary but not sufficient for a diagnosis of AOM; there also must be
bulging of the tympanic membrane or other signs of acute inflammation. If a child has
MEE but no evidence of acute inflammation, he or she has OME.

Etiologic diagnosis Tympanocentesis (aspiration of the middle ear fluid) for culture is
required for etiologic diagnosis. Etiologic diagnosis is not necessary in most cases of AOM
since the antimicrobial agent can be chosen empirically. However, tympanocentesis is
warranted if the patient with AOM appears toxic, has immune deficits, or has failed
previous courses of antibiotic therapy. (See "Acute otitis media in children: Treatment",
section on 'Treatment failure'.)

DIFFERENTIAL DIAGNOSIS The main consideration in the differential diagnosis of


AOM is otitis media with effusion (OME).

Otitis media with effusion Middle ear effusion (MEE) with decreased mobility and
opacification or cloudiness of the tympanic membrane occurs in both AOM and OME.
However, careful evaluation of the position, color, and other findings of the tympanic
membrane can help to distinguish AOM from OME [20]. (See 'Otoscopy' above.)

In AOM, the tympanic membrane is usually bulging (picture 4); in OME, it is usually
retracted (picture 7) or in the neutral position.
In AOM, the tympanic membrane is typically white or pale yellow; in OME, it is
typically amber or blue.
In AOM, pus may be visualized behind the tympanic membrane (picture 4); the
tympanic membrane may be perforated with acute purulent otorrhea, or bullae may
be present. In OME, a fluid level (picture 6) or bubbles may be seen.

Other conditions Other conditions share some of the otoscopic and nonotoscopic
features of AOM, but the history and physical examination should readily distinguish these
conditions from AOM. (See "External otitis: Pathogenesis, clinical features, and
diagnosis".)

Redness of tympanic membrane Redness of the tympanic membrane may be


caused by crying, high fever, upper respiratory infection with congestion and
inflammation of the mucosa lining the entire respiratory tract, trauma, and/or cerumen
removal. (See 'Color' above.)
Decreased or absent mobility of tympanic membrane In addition to AOM and
OME, decreased or absent mobility of the tympanic membrane may be caused by
tympanosclerosis (picture 5) or a high negative pressure within the middle ear cavity.
(See 'Mobility' above and 'Other findings' above.)
Ear pain Ear pain may be caused by otitis externa, ear trauma, throat infections,
foreign body, or temporomandibular joint syndrome. (See "Evaluation of earache in
children".)

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Acute otitis media and otitis media with effusion in children".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

Basics topic (see "Patient education: Ear infections (otitis media) (The Basics)")
Beyond the Basics topic (see "Patient education: Ear infections (otitis media) in
children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS


Acute otitis media (AOM) is defined by acute bacterial infection of middle ear fluid; it
must be distinguished from otitis media with effusion (OME), which is defined by fluid
in the middle ear cavity that is not infected. (See 'Terminology' above.)
Accurate diagnosis of AOM is facilitated by competent skills in pneumatic otoscopy
and adherence to stringent diagnostic criteria. (See 'Importance of accurate
diagnosis' above.)
The key to distinguishing AOM from OME is the performance of otoscopy using
appropriate tools and an adequate light source; otoscope bulbs should be replaced at
least every two years. (See 'Otoscopy' above.)
Systematic assessment of the tympanic membrane includes evaluation of position,
translucency, mobility, color, and other findings (eg, air-fluid levels).
(See 'Overview' above.)
Clinical diagnosis of AOM requires either a bulging tympanic membrane or, very
infrequently, other signs of acute inflammation and evidence of middle ear effusion
(MEE). A diagnosis of AOM also can be established if the tympanic membrane has
perforated, acute purulent otorrhea is present, and otitis externa has been excluded.
(See 'Clinical diagnosis' above.)
MEE, which may indicate either OME or AOM, can be confirmed by the observation
of bubbles or an air-fluid level (picture 6), or at least two of the following (see 'Clinical
diagnosis' above):
Abnormal color (white, yellow, amber, or blue)
Opacity not due to tympanosclerosis (involving part or all of the tympanic
membrane)
Impaired mobility (movie 2)

Acute otitis media in children: Treatment

Authors:
Jerome O Klein, MD
Stephen Pelton, MD
Section Editors:
Morven S Edwards, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jan 24, 2017.
INTRODUCTION Acute otitis media (AOM), also called purulent otitis media and
suppurative otitis media, occurs frequently in children. It is the most common diagnosis for
which they receive antibiotics [1,2].

The treatment of uncomplicated AOM will be reviewed here. The epidemiology,


pathogenesis, diagnosis, complications, and prevention of AOM are discussed separately,
as is otitis media with effusion (serous otitis media).

(See "Acute otitis media in children: Epidemiology, microbiology, clinical


manifestations, and complications".)
(See "Acute otitis media in children: Diagnosis".)
(See "Acute otitis media in children: Prevention of recurrence".)
(See "Otitis media with effusion (serous otitis media) in children: Clinical features
and diagnosis".)
(See "Otitis media with effusion (serous otitis media) in children: Management".)

DIAGNOSIS OF AOM The clinical diagnosis of acute otitis media (AOM) requires
bulging of the tympanic membrane or other signs of acute inflammation and middle ear
effusion (picture 1) [3,4]. (See "Acute otitis media in children: Diagnosis", section on
'Diagnosis'.)

The importance of accurate diagnosis of AOM cannot be overstated. Accurate diagnosis


ensures appropriate treatment for children with AOM, who require antibiotic therapy, and
avoidance of antibiotics in children with otitis media with effusion, in whom antibiotics are
unnecessary. Accurate diagnosis also prevents overuse of antibiotics, which leads to an
increased prevalence of resistant organisms.

CLINICAL COURSE With appropriate antibiotic therapy, the systemic and local signs
and symptoms of acute otitis media (AOM) usually resolve in 24 to 72 hours [5,6].
Symptoms and signs resolve more slowly in children who are managed with analgesia and
observation initially. In a 2013 meta-analysis of seven randomized trials and three
observational studies (1409 children), ear pain resolved within three days in 50 percent of
children and within seven to eight days in 90 percent of children who did not receive
antibiotic therapy [7].

Whether initially treated with antibiotics or not, persistence of middle ear effusion after the
resolution of acute symptoms is common. In a prospective study of 2565 children followed
from birth, middle ear effusion (diagnosed via pneumatic otoscopy) persisted for weeks to
months after the onset of AOM [8]. At two weeks, 70 percent still had effusion; at one
month, 40 percent still had effusion; at two months, 20 percent still had effusion; and at
three months, 10 percent still had effusion (figure 1).

The clinical features, complications, and management of persistent middle ear effusion are
discussed separately. (See "Otitis media with effusion (serous otitis media) in children:
Clinical features and diagnosis" and "Otitis media with effusion (serous otitis media) in
children: Management".)

SYMPTOMATIC THERAPY

Systemic and topical analgesics Pain is a common feature of acute otitis media
(AOM) and may be severe [5]. We recommend treatment to reduce ear pain in children
with AOM whether or not they are treated with antibiotics [3].

We suggest oral ibuprofen or acetaminophen for pain control in children with AOM.
Topical benzocaine, procaine, or lidocaine preparations (if available) are an alternative for
children 2 years but should not be used in children with tympanic membrane perforation.
Topical benzocaine is avoided in children <2 years because of the risk of
methemoglobinemia [9]. Topical benzocaine products have been withdrawn from the
market in the United States because they have not been evaluated by the US Food and
Drug Administration (FDA) for safety, effectiveness, and quality [10]. (See "Topical
anesthetics in children", section on 'Benzocaine'.)

In a 2016 systematic review of nonsteroidal antiinflammatory drugs and acetaminophen for


pain relief in AOM, fewer children who received oral ibuprofen or acetaminophen than
placebo had pain at 48 hours (7, 10, and 25 percent, respectively [one trial, 219
participants]) with no difference in the rate of adverse effects [11]. Ibuprofen and
acetaminophen appeared to be equally effective, although data were limited (two trials, 39
participants), and data were insufficient to draw firm conclusions regarding the efficacy of
combined ibuprofen and acetaminophen versus acetaminophen alone.

The efficacy of topical benzocaine and lidocaine in reducing AOM-associated ear pain has
also been evaluated in randomized trials [12]. In a trial in which 54 children (5 to 19 years)
who presented to an emergency department with ear pain and AOM were randomly
assigned to treatment with a topical benzocaine preparation or olive oil placebo, more
children in the treatment group reported a 25 percent reduction in ear pain score 30
minutes after treatment (96 versus 70 percent) [13].

In a similar trial in 63 children (3 to 12 years) randomly assigned to topical


aqueous lidocaine (lignocaine) or saline, patient-reported pain scores in lidocaine
recipients were consistently reduced by at least 25 percent during the first 30 minutes
following application [14]. No adverse effects were reported. Further studies of lidocaine
are needed to optimize the dose, as well as identify the duration of pain relief and the
effectiveness in younger children.

Decongestants and antihistamines We recommend not using


decongestants and/or antihistamines in the symptomatic management of AOM in children.

Studies of the efficacy of antihistamines and decongestants in treating AOM suggest a lack
of benefit and a potential for delayed resolution of middle ear fluid. A 2007 systematic
review found that decongestants and antihistamines alone or in combination were
associated with increased medication side effects and did not improve healing or prevent
surgery or other complications in AOM [15]. In addition, treatment with antihistamines may
prolong the duration of middle ear effusion [16].

In children with AOM and known or suspected nasal allergy, an oral decongestant or
antihistamine may provide symptomatic relief of nasal congestion. When treating such
children, practitioners should weigh the potential symptomatic benefit against the reported
adverse events and potential for prolongation of middle ear effusion.
(See "Pharmacotherapy of allergic rhinitis", section on 'Approach to specific patient
groups'.)

The American Academy of Pediatrics (AAP) recommends that over-the-counter cough and
cold medications not be given to infants and children <6 years of age because of the risk
of life-threatening side effects [17,18]. (See "The common cold in children: Management
and prevention", section on 'Over-the-counter medications'.)

Other therapies We do not suggest distraction, external application of heat or cold, or


instillation of olive oil or herbal extracts into the external auditory canal to treat pain in
children with AOM. These therapies have been proposed, but there are no placebo-
controlled trials that directly address their effectiveness [3].

A topical herbal extract (containing Allium sativum [garlic], Verbascum


thapsus [mullein], Calendula flores [marigold], and Hypericum perforatum [St. John's wort]
in olive oil) was compared with topical anesthetic treatment in a randomized trial of 103
children (6 to 18 years) with AOM-associated pain [19]. Both groups experienced
comparable improvements in pain throughout the three days of the study, but there was no
placebo group.

ANTIBIOTIC THERAPY VERSUS OBSERVATION In addition to pain control, there are


two strategies for initial management of acute otitis media (AOM): 1) immediate treatment
with antibiotics and 2) observation with initiation of antibiotic therapy if the symptoms and
signs worsen or fail to improve after 48 to 72 hours.

The choice of strategy depends upon the age of the child and the severity of illness:

We recommend that children <6 months with AOM be treated immediately with an
appropriate antibiotic. (See 'Initial antimicrobial therapy' below.)
Febrile infants younger than 60 days who are diagnosed with AOM may require
additional evaluation before initiation of antimicrobial therapy to avoid masking an
invasive bacterial infection. (See "Febrile infant (younger than 90 days of age):
Outpatient evaluation", section on 'Ancillary studies'.)
We suggest that children six months to two years with bilateral AOM be treated
immediately with an appropriate antibiotic. We also suggest antibiotic treatment for
children six months to two years with unilateral AOM.
For children six months to two years with unilateral AOM and mild symptoms, the
American Academy of Pediatrics (AAP) guideline (2013) permits initial observation
after joint decision-making with the parent(s)/caregiver [3]. However, given the high
rate of treatment failure among children <24 months with unilateral nonsevere AOM
who are initially managed with observation and analgesia [20], we suggest that such
children be treated with antimicrobial therapy. (See 'Initial antimicrobial
therapy' below.)
We suggest that children 2 years who appear toxic; have persistent otalgia for
more than 48 hours; have temperature 102.2F (39C) in the past 48 hours; have
bilateral AOM or otorrhea; or have uncertain access to follow-up be immediately
treated with an appropriate antibiotic. (See 'Initial antimicrobial therapy' below.)
For children 2 years who are normal hosts (eg, immune competent, without
craniofacial abnormalities) with mild symptoms and signs and no otorrhea, initial
observation may be appropriate if the caretakers understand the risks and benefits of
such an approach. (See 'Initial observation' below.)

The treatment of otorrhea in children with tympanostomy tubes is discussed separately.


(See "Tympanostomy tube otorrhea in children: Causes, prevention, and management",
section on 'Treatment'.)

In a 2006 meta-analysis of individual data from six high-quality randomized trials (1643
children age 6 months to 12 years), children who were younger than two years who had
bilateral AOM and children with otorrhea benefited most from antibiotic therapy [5]. Among
children younger than two years with bilateral AOM, 25 percent (95% CI 14-36 percent)
fewer children treated with antibiotics than with symptomatic care continued to have
pain and/or fever on days three to seven of illness. Among children with otorrhea, 36
percent (95% CI 19-53 percent) fewer children treated with antibiotics than with
symptomatic care continued to have pain and/or fever on days three to seven of illness.

A 2015 meta-analysis of 13 randomized trials (3401 children, 3938 episodes of AOM)


comparing antibiotics with placebo found [6]:

Antibiotics reduced pain at two to three days (seven trials, 2320 patients): 11.6
versus 15.9 percent (relative risk [RR] 0.70 95% CI 0.57-0.86)
Antibiotics reduced tympanic membrane perforations (five trials, 1075 patients): 1.9
versus 4.8 percent (RR 0.37 95% CI 0.18-0.76)
Antibiotics reduced contralateral episodes of AOM (four trials, 906 patients): 10.6
versus 18.8 percent (RR 0.49 95% CI 0.25-0.95)
Antibiotics did not affect the rate of late recurrence (six trials, 2200 patients):
approximately 20 percent
Antibiotics increased adverse events (vomiting, diarrhea, or rash): 27.1 versus 19.6
percent (RR 1.38 95% CI 1.19-1.59)
Serious complications (eg, mastoiditis, meningitis) were rare in both the treatment
and placebo groups

Randomized trials comparing immediate versus delayed antibiotics have used different
outcome measures (eg, parental satisfaction, rate of filled prescriptions, etc) and types of
follow-up (eg, telephone versus office examination), but also document earlier resolution of
symptoms and signs of tympanic membrane inflammation among children who receive
immediate treatment [21-26].

Systematic reviews and meta-analyses suggest that many children with AOM do well with
initial observation and analgesia only, and that the benefits of antibiotics are modest [6,27-
30]. However, many of the studies included in the meta-analyses had increased risk of
bias (related to nonstringent diagnostic criteria, inclusion of children with mild disease,
exclusion of patients <2 years of age, use of an inappropriate antibiotic or inappropriate
dose, etc), making the results difficult to interpret [31-34]. Exclusion of children with severe
symptoms biases toward the null hypothesis (ie, no difference between early antimicrobial
treatment and observation).

Individual randomized trials that used stringent diagnostic criteria and experienced
otoscopists to make the diagnosis of AOM and appropriate antibiotic regimens to treat
AOM indicate that children younger than two years benefit from antibiotic therapy [35,36].
Pooled data from these trials indicate increased rates of treatment failure among placebo
recipients <24 months with unilateral nonsevere AOM (40 versus 14 percent among
antibiotic recipients; relative risk 0.34, 95% CI (0.18-0.65) [20]. These and other
randomized trials suggest that children with "severe" (defined by fever and ear pain score)
or bilateral AOM also benefit from antibiotic therapy [20,37,38].

The 2013 AAP and American Academy of Family Physicians (AAFP) guideline
recommends immediate antimicrobial treatment for children <6 months, children with
severe signs or symptoms (defined by moderate or severe ear pain, ear pain for 48
hours, or temperature 39C [102.2F]) and bilateral AOM in children <24 months of age
[3]. The 2013 AAP/AAFP guideline recommends either immediate treatment or
observation (with pain control) for children between 6 and 24 months with unilateral
nonsevere AOM and for children 24 months with unilateral or bilateral nonsevere AOM.
However, given the additional analysis now available showing a high rate of treatment
failure among children <24 months with unilateral nonsevere AOM [20], we suggest that
such children be treated at the time of diagnosis with antimicrobial therapy.

Guidelines from many other countries (eg, the Dutch College of General Practitioners)
recommend a no or delayed antibiotic strategy for most children 6 months of age with
AOM.
INITIAL ANTIMICROBIAL THERAPY When the decision is made to treat acute otitis
media (AOM) with antimicrobial agents, the selection among available drugs (table 1) is
based upon:

Clinical and microbiologic efficacy


Acceptability (taste, texture) of the oral preparation
Absence of side effects and toxicity
Convenience of the dosing schedule
Cost

First-line therapy

No recent beta-lactam therapy, no concomitant purulent conjunctivitis, and no


history of recurrent AOM We suggest amoxicillin as the first-line therapy for
children with AOM who are treated with antibiotics and at low-risk for amoxicillin
resistance (ie, have not received a beta-lactam antibiotic in the previous 30 days, do
not have concomitant purulent conjunctivitis, and have no history of recurrent AOM).
The dose is 90 mg/kg per day divided in two doses (we suggest a maximum of
3 g/day).
Recent beta-lactam therapy, concomitant purulent conjunctivitis, or history of
recurrent AOM We suggest amoxicillin-clavulanate as the first-line therapy for
children with AOM who are treated with antibiotics and at increased risk of beta-
lactam resistance (ie, have received a beta-lactam antibiotic in the previous 30 days,
have concomitant purulent conjunctivitis, which is usually caused by
nontypeable Haemophilus influenzae, or have a history of recurrent AOM as
nontypeable H. influenzae is dominant in recurrent episodes) [39-42]. The dose is
90 mg/kg per day of amoxicillin and 6.4 mg/kg per day of clavulanate divided in two
doses (we suggest a maximum daily dose of the amoxicillin component of 3 g).
Adolescents 16 years who can take large tablets can use extended-release
amoxicillin-clavulanate 1 to 2 g of amoxicillin and 62.5 to 125 mg of clavulanate every
12 hours.

Initial antimicrobial therapy for children with penicillin allergy are discussed below.
(See 'Penicillin allergy' below.)

A 2001 meta-analysis concluded there is no evidence to support any particular antibiotic


regimen versus another for treatment of AOM [27]. Amoxicillin 90 mg/kg per day divided in
two doses (we suggest a maximum of 3 g/day) is the first-line drug of choice because it is
effective, safe, relatively inexpensive, and has a narrow microbiologic spectrum [3,43].

Increasing the dose of amoxicillin from 40 mg/kg per day to 90 mg/kg per day increases
the concentration of amoxicillin in the middle ear [44]. The increased concentrations
provide activity against most intermediate strains of Streptococcus pneumoniae, as well as
many of the resistant strains. Only S. pneumoniae that are highly resistant to penicillin,
approximately 2 percent of pneumococcal isolates using a breakpoint of 8 mcg/mL for
highly resistant, will not respond to high-dose amoxicillin [3,45].

Despite the increasing importance of H. influenzae, including beta-lactamase-producing


strains, high-dose amoxicillin remains the preferred choice for initial therapy in children
who have not a beta-lactam antibiotic in the previous 30 days and do not have concurrent
purulent conjunctivitis [3]. Continued monitoring of the microbiology of AOM is necessary
to determine when and if a change in first-line therapy is necessary. The presence of beta-
lactamase negative, ampicillin-resistant strains in the community is a potential concern.
These strains require minimal inhibitory concentrations of amoxicillin that may be at the
upper limit of what is achievable in the middle ear. Such isolates remain uncommon in the
United States, but have become common in France and Japan [46]. (See "Acute otitis
media in children: Epidemiology, microbiology, clinical manifestations, and complications",
section on 'Bacteria'.)

In a 2013 meta-analysis of five trials (1601 children <12 years), once or twice daily dosing
with amoxicillin or amoxicillin-clavulanate was similar to three times daily dosing in clinical
cure of AOM, recurrence of AOM, and adverse effects [47]. We suggest twice daily dosing
based on pharmacokinetic and pharmacodynamic principles, results of double
tympanocentesis (ie, before and after treatment) studies demonstrating middle ear
sterilization with twice daily regimens, and the lack of any substantial data with once daily
regimens (only 33 patients in the meta-analysis received once daily therapy) [48,49].

Penicillin allergy Acceptable alternatives to penicillin in patients with allergy to


penicillin depend upon the type of the previous hypersensitivity reaction. (See "Penicillin
allergy: Immediate reactions" and "Penicillin-allergic patients: Use of cephalosporins,
carbapenems, and monobactams".)

Delayed reaction For children who report penicillin allergy but who did not experience
an immediate type 1 hypersensitivity reaction (anaphylaxis, angioedema, bronchospasm,
or urticaria), we suggest one of the following:

Cefdinir 14 mg/kg per day orally in one or two doses (maximum 600 mg/day)
Cefpodoxime 10 mg/kg orally in two doses (maximum 400 mg/day)
Cefuroxime suspension 30 mg/kg per day orally divided in two doses (maximum
1 g/day)
Cefuroxime tablets 250 mg orally every 12 hours
Ceftriaxone 50 mg/kg intramuscularly once per day (maximum 1 g/day) for one to
three doses (if there is symptomatic improvement within 48 hours of the first dose,
additional doses are not necessary; if symptoms persist, a second, and if necessary,
a third dose are administered [50])

The oral regimens do not achieve sufficient concentration in the middle ear to eradicate
penicillin-resistant S. pneumoniae.
Immediate reaction Macrolide or lincosamide antibiotics can be used to treat AOM in
children who have had an immediate type 1 hypersensitivity reaction (anaphylaxis,
angioedema, bronchospasm, or urticaria) to amoxicillin or other beta-lactam antimicrobial
agents. However, macrolide or lincosamide resistance is common (approximately 25 to 35
percent) among isolates of S. pneumoniae, and macrolides and lincosamides generally
are not effective for eradication of H. influenzae [46,51,52].

Macrolides and lincosamides available for the treatment of AOM include:

Azithromycin 10 mg/kg per day orally (maximum 500 mg/day) as a single dose on
day one and 5 mg/kg per day (maximum 250 mg/day) for days two through five
Clarithromycin 15 mg/kg per day orally divided into two doses (maximum 1 g/day)
Erythromycin-sulfisoxazole 50 mg/kg per day orally of the erythromycin component
divided into three to four doses (maximum 2 g/day erythromycin or
6 g/day sulfisoxazole); erythromycin plus sulfisoxazole is often rejected by patients
based upon taste and frequency of dosing [53]
The optimal dose for clindamycin therapy for AOM is uncertain; the American
Academy of Pediatrics (AAP) suggests a dose of 10 to 25 mg/kg per day orally
divided in three doses (maximum 1.8 g/day) for mild to moderate infections and 30 to
40 mg/kg per day orally divided in three doses (maximum 1.8 g/day) [3,54]

Increasing the dose of macrolide antibiotics does not overcome macrolide resistance
among pneumococcal isolates (as with beta-lactam drugs) [43].

Trimethoprim-sulfamethoxazole (TMP-SMX) may be useful in regions where


pneumococcal resistance to TMP-SMX is not a concern, but TMP-SMX should not be used
if group A streptococcus (S. pyogenes) is suspected (eg, when there is an associated
tympanic membrane perforation). (See 'AOM with perforation' below.)

AOM with perforation For children with AOM and tympanic membrane perforation, we
suggest oral rather than topical antibiotic therapy. We suggest amoxicillin 90 mg/kg per
day orally divided in two doses (we suggest a maximum of 3 g/day) as the preferred first-
line oral therapy. Because of the possibility of group A streptococcus, an agent other than
TMP-SMX should be used. For patients with acute otorrhea, 10 days of oral therapy is
more effective than a shorter course [55].

Although topical therapy with quinolone otic drops (ofloxacin or ciprofloxacin) is equivalent
to oral therapy for treatment of otorrhea in children with tympanostomy tubes or chronic
suppurative otitis media, topical therapy has not been studied in children with AOM and
acute perforation [56,57]. Nonantimicrobial topical agents, such as benzocaine or olive oil,
should not be used in patients with perforation of the tympanic membrane.
(See "Tympanostomy tube otorrhea in children: Causes, prevention, and management",
section on 'Treatment'.)
Duration of therapy The duration of treatment varies with age, associated clinical
features, and antimicrobial agent:

First line therapy for children with no allergy to penicillin


We treat children <2 years of age, children with AOM and tympanic membrane
perforation, and children with a history of recurrent AOM
with amoxicillin or amoxicillin-clavulanate for 10 days. (See 'First-line
therapy' above.)
We treat children 2 years with AOM, an intact tympanic membrane, and
without recurrent AOM with amoxicillin or amoxicillin-clavulanate for five to seven
days. (See 'First-line therapy' above.)
Second-line therapy
We treat children with a delayed hypersensitivity reaction to penicillin orally with
10 days of cefdinir, cefpodoxime, or cefuroxime. For children with an immediate
type 1 hypersensitivity reaction to penicillin (anaphylaxis, angioedema,
bronchospasm, or urticaria), a five-day course of azithromycin is an acceptable
alternative. (See 'Penicillin allergy' above.)
We treat children who require parenteral therapy with one to three doses
of ceftriaxone, depending upon the clinical response. (See 'Delayed
reaction' above and 'Initial treatment failure' below.)

Most clinical trials and standard pediatric practice provide a 10-day course of an oral
antimicrobial agent for the treatment of AOM [58-61]. However, some data suggest that a
shorter course (ie, seven days) may be adequate for older children [62].

Many of the studies comparing short- and long-term antibiotic therapy had limitations that
precluded definitive conclusions (eg, lack of blinding, failure to use strict diagnostic criteria
or directly compare the same antibiotic agent) [63]. These limitations were addressed in a
trial that randomly assigned 520 children 6 through 23 months of age with strictly defined
AOM to treatment with amoxicillin-clavulanate for 10 days or for five days followed by five
days of placebo [61]. The rate of clinical failure (defined as worsening of symptoms or
otoscopic signs of AOM during treatment or lack of complete/near complete resolution of
symptoms and signs at the end of treatment) was lower among those assigned to 10 days
of treatment (16 versus 34 percent; difference of 17 percentage points [before rounding]
95% CI 9-25). The rate of adverse events did not differ between groups. The trial did not
address duration of treatment in children older than two years.

INITIAL OBSERVATION Initial observation is an alternative to antimicrobial therapy for


children 2 years who are normal hosts (eg, immune competent, without craniofacial
abnormalities), without otorrhea, and who have mild symptoms and signs of unilateral
acute otitis media (AOM) (ie, nonsevere ear pain for <48 hours and temperature <39C
[102.2F]). Clinicians who recommend initial observation should exercise rigor in
diagnosing AOM similar to that in the research protocols that support the safety of this
strategy. (See 'Antibiotic therapy versus observation' above and "Acute otitis media in
children: Diagnosis".)

When the initial observation strategy is chosen, caretakers must understand the risks and
benefits, and appropriate follow-up must be ensured so that antibiotic therapy can be
initiated if symptoms worsen or persist after 48 to 72 hours [3]. Unilateral AOM at first
observation may rapidly progress to bilateral disease during the early hours of illness.
Adequate follow-up may include a parent-initiated visit or phone contact if symptoms
worsen or do not improve at 48 to 72 hours, a scheduled follow-up appointment in 48 to 72
hours, or giving parents an antibiotic prescription that can be filled if illness does not
improve in this time frame [22,23,64-67]. (See 'Follow-up' below.)

The 2013 American Academy of Pediatrics (AAP) and American Academy of Family
Physicians (AAFP) guideline suggests initial observation (with pain control) as an option
for healthy children (ie, without conditions that predispose to AOM) between 6 and 24
months with unilateral nonsevere AOM and for children 24 months with unilateral or
bilateral nonsevere AOM [3]. This is a change from the 2004 guidelines, which suggested
initial observation as an option for children 6 months with "uncertain" diagnosis and
children 2 years with non-severe illness [68].

Guidelines from many other countries (eg, the Dutch College of General Practitioners)
recommend no antibiotics or delayed antibiotics for most children 6 months of age with
AOM.

FOLLOW-UP

Persistent symptoms Children who fail to improve after 48 to 72 hours of antibiotic


therapy should be seen in follow-up to confirm the diagnosis of acute otitis media (AOM),
evaluate other causes of persistent symptoms, and determine whether a change in
antibacterial therapy is warranted [3]. (See 'Treatment failure' below.)

Children who worsen or fail to improve after 48 to 72 hours of initial observation and
symptomatic treatment without antibiotics should be started on antibiotics. (See 'Initial
antimicrobial therapy' above.)

Resolved symptoms Follow-up for children whose symptoms have resolved depends
upon the child's age and underlying medical problems, particularly language delay or
learning problems.

We suggest that:

Children <2 years be seen 8 to 12 weeks after diagnosis (by which time middle ear
effusion will have resolved in 80 to 90 percent (figure 1)); many such children will
already have a routine healthcare visit scheduled within this time frame
Children 2 years who have language or learning problems be seen 8 to 12 weeks
after diagnosis AOM
Children 2 years who are without language or learning problems be followed up at
their next health maintenance visit, or sooner if there are concerns regarding
persistent hearing loss

The main reason for follow-up of children with resolved symptoms is to monitor the
resolution of middle ear effusion which is associated with conductive hearing loss.
Persistent middle ear effusion is common after the resolution of acute symptoms. In a
large prospective study, middle ear effusion persisted for weeks to months after the onset
of AOM in children (figure 1) [8]. (See 'Clinical course' above.)

The management of persistent middle ear effusion is discussed separately. (See "Otitis
media with effusion (serous otitis media) in children: Clinical features and diagnosis",
section on 'Hearing loss' and "Otitis media with effusion (serous otitis media) in children:
Management", section on 'Overview of management'.)

Tympanic membrane perforation Tympanic membrane perforation permits drainage


of the middle ear abscess and relieves increased middle ear pressure. With the relief of
middle ear pressure, the tympanic membrane usually heals quickly, sealing the perforation
in hours to days.

If pain occurs or persists in a child with AOM and tympanic membrane perforation, causes
other than AOM must be considered. The pain is unlikely to be due to AOM because the
pressure of middle ear fluid is relieved when the tympanic membrane is perforated. Other
possible causes include:

Extension of the infection to a contiguous space, such as the mastoid (ie,


mastoiditis) (see "Acute mastoiditis in children: Clinical features and diagnosis",
section on 'Diagnosis' and "Acute mastoiditis in children: Treatment and prevention",
section on 'Overview of management')
Irritation of the external canal from middle ear drainage, resulting in otitis externa, in
which case treatment with a topical quinolone may be beneficial (see "External otitis:
Treatment", section on 'Topical therapy')

Nonantimicrobial topical agents, such as benzocaine or olive oil, should not be used to
treat pain in patients with perforation of the tympanic membrane.

Patients with perforation that persists for three months or longer (with or without
suppurative drainage) should be referred to an otolaryngologist for further management
[69]. Prevention of chronic suppurative otitis media entails prompt and appropriate
treatment of AOM [70]. Chemoprophylaxis is not warranted. (See "Chronic suppurative
otitis media (CSOM): Clinical features and diagnosis" and "Chronic suppurative otitis
media (CSOM): Treatment, complications, and prevention".)
TREATMENT FAILURE

Definition and etiology Treatment failure is defined by lack of improvement by 48 to


72 hours in a patient treated with antimicrobial therapy.

Fluid may persist in the middle ear for prolonged periods, even when the antimicrobial
agents have sterilized the effusion and the acute signs and symptoms are no longer
present. Persistent middle ear effusion after the resolution of acute symptoms is not an
indication of treatment failure or an indication for additional antibiotic therapy [71].
(See 'Clinical course' above.)

Treatment failure suggests either the initial therapy was not adequate or another disease is
present. (See 'Approach' below and "Acute otitis media in children: Diagnosis", section on
'Differential diagnosis'.)

Inadequate therapy is usually related to infection with an organism resistant to beta-lactam


antibiotics (nontypeable H. influenzae and drug-resistant S. pneumoniae are becoming
increasingly important), but infection with less common organisms, such
as Staphylococcus aureus, also must be considered, particularly in children with
tympanostomy tubes or perforation [72-74]. (See "Acute otitis media in children:
Epidemiology, microbiology, clinical manifestations, and complications", section on
'Microbiology' and "Tympanostomy tube otorrhea in children: Causes, prevention, and
management", section on 'Pathogens'.)

Approach

Initial treatment failure

Patients initially treated with amoxicillin We suggest that patients who fail
treatment with high-dose amoxicillin be treated with amoxicillin-clavulanate [3]. The
dose is 90 mg/kg per day amoxicillin and 6.4 mg/kg per day of clavulanate divided in
two doses (we suggest a maximum of 3 g/day). Adolescents 16 years who can take
large tablets can use extended-release amoxicillin-clavulanate 1 to 2 g of the
amoxicillin component and 62.5 to 125 mg of the clavulanate component every 12
hours.
We prefer amoxicillin-clavulanate for children who fail treatment
with amoxicillin because of its efficacy against beta-lactamase-producing H.
influenzae and Moraxella catarrhalis; for S. pneumoniae, amoxicillin and amoxicillin-
clavulanate have equivalent efficacy.
Patients initially treated with amoxicillin-clavulanate and without immediate
reaction to amoxicillin Alternatives to high-dose amoxicillin-clavulanate for patients
without immediate reaction to penicillin include cephalosporins or quinolones.
However, with the exception of ceftriaxone, the alternative cephalosporins are less
potent against penicillin-resistant S. pneumoniae:
Cefdinir 14 mg/kg per day orally in one or two doses (maximum
600 mg/day) [75].
Cefpodoxime 10 mg/kg orally in two doses (maximum 400 mg/day).
Cefuroxime suspension 30 mg/kg per day orally divided in two doses (maximum
1 g/day); the spectrum of activity of cefuroxime is excellent for AOM; however,
because children may find it unpalatable [53,76], its usefulness as a second-line
agent may be limited [50].
Cefuroxime tablets 250 mg orally every 12 hours.
Ceftriaxone 50 mg/kg intramuscularly or intravenously once per day
(maximum 1g/day) for one to three doses (if there is symptomatic improvement
within 48 hours of first dose, additional doses are not necessary; if symptoms
persist, a second, and if necessary, a third dose are administered [50]).
Parenteral ceftriaxone 50 mg/kg achieves high levels in the middle ear and is
effective for the treatment of AOM in children who fail amoxicillin [3]; although the
US Food and Drug Administration (FDA) has approved a single dose of
parenteral ceftriaxone for the treatment of AOM in children, an open-label
prospective study suggested that three doses were superior in eradicating
penicillin-resistant S. pneumoniae from the middle ear [77].
Levofloxacin 10 mg/kg orally every 12 hours for 10 days for children six months
to five years or 10 mg/kg per orally once daily for 10 days for children 5 years
(maximum 500 to 750 mg/day) [78].
Levofloxacin should be reserved for children with AOM refractory to other drugs
(ideally it should only be used in children who have had serotype 19A isolated
from the middle ear that is susceptible to levofloxacin) [74]; levofloxacin is not
approved by the FDA for the treatment of AOM, and levofloxacin resistance
among S. pneumoniae respiratory isolates has been described in adults and
rarely in children [79].
Trimethoprim-sulfamethoxazole (TMP-SMX), macrolides (eg, erythromycin-
sulfisoxazole, azithromycin, clarithromycin), and lincosamides (eg, clindamycin) are
not recommended for AOM that fails to respond to treatment with high-
dose amoxicillin or amoxicillin-clavulanate. Pneumococcal surveillance studies
indicate that resistance to these agents is substantial [45,80]. Macrolides and
lincosamides have limited activity against nontypeable H. influenzae, which is a more
likely pathogen among children who have failed initial amoxicillin therapy.
Patients initially treated with macrolides or clindamycin The management of
treatment failure in children with AOM and immediate hypersensitivity reactions to
penicillin who were initially treated with macrolides or clindamycin is challenging. The
pathogens most likely in this scenario are nontypeable H. influenzae (either beta
lactamase-positive or beta lactamase negative) or multidrug resistant S. pneumoniae.
Consultation with a pediatric infectious diseases expert and/or pediatric
otolaryngologist may be warranted.
Our suggested approach is as follows:
Tympanocentesis (if available), which will provide relief of ear pain and permit
culture and susceptibility testing to guide antimicrobial selection. Concomitant
placement of a tympanostomy tube may be warranted. A discussion of the
tympanocentesis procedure is beyond the scope of this topic review, but is
available in reference [81].
If tympanocentesis is not available, we suggest levofloxacin 10 mg/kg orally
every 12 hours for 10 days for children six months to five years or 10 mg/kg per
orally once daily for 10 days for children 5 years (maximum 500 to
750 mg/day) [78]. Levofloxacin is not approved by the FDA for the treatment of
AOM and should be reserved for AOM refractory to other drugs.
Most nontypeable H. influenzae are susceptible to TMP-SMX, but susceptibility of S.
pneumoniae varies geographically. TMP-SMX may be an option in areas with high
rates of susceptibility.

Persistent treatment failure Referral to a pediatric otolaryngologist and/or pediatric


infectious diseases expert may be warranted for children with persistent treatment failure.
Tympanocentesis is recommended to make a bacteriologic diagnosis if symptoms persist
despite ceftriaxone or other broad spectrum therapies [74]. Tympanocentesis should be
performed by an appropriately trained clinician who is comfortable performing the
procedure in an awake child (unless there is access to sedation or anesthesia).
Alternatively, treatment with levofloxacin and/or tympanostomy tube placement may be
appropriate [74].

RECURRENT AOM Recurrent acute otitis media (AOM) is defined by the development
of signs and symptoms of AOM soon after completion of successful treatment. It is
particularly important to establish the diagnosis of recurrent AOM with bulging of the
tympanic membrane and signs of inflammation. Otherwise, persistent middle ear effusion
in a child with a febrile upper respiratory infection may be misinterpreted as a recurrent
episode and the child may receive antibiotics unnecessarily.

There are no randomized trials to guide treatment of recurrent AOM in children. The
approach varies depending upon the therapy that was used for recent episodes. Treatment
of recurrent AOM must include coverage for resistant pathogens, particularly S.
pneumoniae.

When recurrence occurs within 15 days of completion of antimicrobial treatment for the
previous episode, we suggest:

Ceftriaxone 50 mg/kg per day intramuscularly (IM) or intravenously (IV) for three
days, or
Ceftriaxone 50 mg/kg per dose IM or IV every 36 hours for a total of two doses, or
Levofloxacin 10 mg/kg every 12 hours orally for 10 days for children six months to
five years or 10 mg/kg per once daily for 10 days for children 5 years (maximum 500
to 750 mg/day) [78]
When the recurrence occurs more than 15 days after completion of the treatment for the
previous episode, it is most often due to a different pathogen than the previous episode.
Although the child is at higher risk for a nonsusceptible pathogen, we suggest high
dose amoxicillin-clavulanate as initial therapy, even if the child received amoxicillin-
clavulanate for the previous episode.

Tympanostomy tube insertion may be warranted for children with 3 distinct and well-
documented episodes of AOM within six months or 4 episodes within 12 months if middle
ear fluid is also present [82]. (See "Acute otitis media in children: Prevention of
recurrence", section on 'Tympanostomy tubes'.)

TREATMENT OF AOM COMPLICATIONS Acute otitis media (AOM) may be


associated with intratemporal or intracranial complications. The treatment of these
complications is discussed separately:

Cholesteatoma (see "Cholesteatoma in children", section on 'Surgical treatment')


Mastoiditis, which may be complicated by petrositis (osteomyelitis of the petrous
bone) (see "Acute mastoiditis in children: Treatment and prevention")
Facial nerve palsy, which may be isolated or associated with osteomyelitis of the
petrous bone (see "Facial nerve palsy in children", section on 'Treatment' and "Acute
mastoiditis in children: Treatment and prevention", section on 'Complicated disease')
Meningitis (see "Bacterial meningitis in children older than one month: Treatment
and prognosis")

AIRPLANE TRAVEL Children with Eustachian tube dysfunction, including those with
acute otitis media (AOM), may have pain during airplane descent [83,84]. Most
commercial airplanes have pressurized cabins, with the pressure equal to that at 7000 to
10,000 feet. During the flight, middle ear pressure gradually equilibrates through
swallowing or absorption of air by the middle ear mucosa. With airplane descent, the
pressure in the cabin increases to that at landing altitude. If middle ear pressure does not
increase accordingly (ie, if the Eustachian tube "locks in" the reduced pressure, due to
obstruction of the nasopharyngeal orifice), the tympanic membrane may be forced
medially and stretched, which can lead to painful barotrauma: bleeding into the tympanic
membrane (picture 2), formation of fluid exudates in the middle ear, and occasionally to
tympanic membrane rupture [85]. Upper respiratory infection appears to be a predisposing
condition for aerotitis (inflammation of the ear caused by changes in atmospheric pressure,
also known as barotitis). (See "Ear barotrauma", section on 'Etiology'.)

Interventions to equalize middle ear and atmospheric pressure have not been well studied
in controlled trials. We suggest that children be awake during descent and chewing gum or
food (or sucking on a pacifier or bottle if they are too young to chew gum or food) to open
the Eustachian tube and facilitate equalization of middle ear pressure [86]. Autoinflation via
the Valsalva maneuver (forced exhalation with the mouth and nose closed) or a purpose-
manufactured nasal balloon also may be helpful in older children [87]. In younger children,
nasal bulb suction may be helpful. We do not suggest preflight treatment with
antihistamines or decongestants. In a randomized trial, predeparture administration
of pseudoephedrine did not decrease ear pain, but was associated with increased
drowsiness [88].

There is little published information describing other adverse effects of airplane travel in
children with AOM. However, there are no reports of extratemporal extension of AOM
related to flying.

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Acute otitis media and otitis media with effusion in children".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Ear infections (otitis media) (The
Basics)" and "Patient education: Ruptured eardrum (The Basics)")
Beyond the Basics topic (see "Patient education: Ear infections (otitis media) in
children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

The diagnosis of acute otitis media (AOM) requires bulging of the tympanic
membrane or other signs of acute inflammation and middle ear effusion (picture 1).
The importance of accurate diagnosis is crucial to avoidance of unnecessary
treatment. (See 'Diagnosis of AOM' above and "Acute otitis media in children:
Diagnosis", section on 'Diagnosis'.)
We suggest oral ibuprofen or acetaminophen to treat ear pain in children with AOM
(Grade 2B). Topical benzocaine, procaine, or lidocaine preparations (if available) are
an alternative for children 2 years, but should not be used in children with tympanic
membrane perforation. We recommend NOT using
decongestants and/or antihistamines (Grade 1A). (See 'Symptomatic
therapy' above.)
The choice of initial treatment with antibiotics or observation depends upon the age
of the child and the laterality and severity of illness (see 'Antibiotic therapy versus
observation' above):
We recommend that children with AOM who are <6 months be treated with
antibiotics (Grade 1A).
We suggest that children with AOM who are between six months and two years
be treated with antibiotics (Grade 2A).
We suggest that children 2 years who appear toxic; have persistent otalgia for
more than 48 hours; have temperature 102.2F (39C) in the past 48 hours;
have bilateral AOM or otorrhea; or have uncertain access to follow-up be
immediately treated with an appropriate antibiotic (Grade 2A). (See 'Initial
antimicrobial therapy' above.)
For children 2 years who are normal hosts (eg, immune competent, without
craniofacial abnormalities) and have unilateral AOM with mild symptoms and
signs and no otorrhea, initial observation may be appropriate if the caretakers
understand the risks and benefits of such an approach.
When antibiotic treatment is warranted, we suggest amoxicillin as the first-line
therapy for AOM in most children (Grade 2B). The dose is 90 mg/kg per day (we use
a maximum of 3 g/day) divided in two doses. We suggest amoxicillin-clavulanate as
the first-line therapy for children with AOM who have received a beta-lactam antibiotic
in the previous 30 days or have concomitant purulent conjunctivitis (Grade 2A). The
dose is 90 mg/kg per day of amoxicillin and 6.4 mg/kg per day of clavulanate divided
in two doses. (See 'First-line therapy' above.)
Macrolides or clindamycin are an alternative for patients who have had immediate
hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchospasm, urticaria) to
penicillin (table 1). However, macrolides and clindamycin lack activity against
most Haemophilus influenzae isolates and approximately one-third of pneumococcal
isolates. Patients with other types of allergic reactions may be treated safely
with cefdinir, cefpodoxime, cefuroxime, or intramuscular ceftriaxone. (See 'Penicillin
allergy' above.)
We generally treat children <2 years, children with tympanic membrane perforation,
and children with recurrent AOM for 10 days. We generally treat children 2 years
without a history of recurrent AOM for five to seven days. (See 'Duration of
therapy' above.)
Treatment failure is defined by lack of symptomatic improvement 48 to 72 hours
after initiation of antimicrobial therapy. We suggest that patients who fail first-line
therapy be treated with amoxicillin-clavulanate (Grade 2B). Alternatives
include cefdinir, cefpodoxime, cefuroxime, and ceftriaxone. (See 'Initial treatment
failure' above.)
Acute otitis media in children: Prevention of recurrence

Authors:
Jerome O Klein, MD
Stephen Pelton, MD
Section Editors:
Sheldon L Kaplan, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Oct 18, 2016.

INTRODUCTION Prevention is an important part of the management strategy for the


child with severe and recurrent acute otitis media (AOM) and the child who is at risk for
severe and recurrent AOM.

The prevention of AOM will be reviewed here. Other topics related to otitis media are
presented separately:

(See "Acute otitis media in children: Epidemiology, microbiology, clinical


manifestations, and complications" and "Acute otitis media in children:
Diagnosis" and "Acute otitis media in children: Treatment".)
(See "Otitis media with effusion (serous otitis media) in children: Clinical features
and diagnosis" and "Otitis media with effusion (serous otitis media) in children:
Management".)
(See "External otitis: Pathogenesis, clinical features, and diagnosis" and "External
otitis: Treatment".)
(See "Malignant (necrotizing) external otitis".)

DEFINITIONS Recurrent AOM is usually defined as 3 distinct and well-documented


episodes of AOM within six months or 4 episodes within 12 months [1-3]. Children with
recurrent AOM are also referred to as "otitis prone" [4].

Infants who have their first episode before six months of age or who have siblings with
severe and recurrent AOM are at highest risk for severe and recurrent AOM. It remains
unresolved as to whether early disease damages the Eustachian tube or middle ear
leading to recurrent disease or selects those with anatomic or genetic predisposition to
recurrent disease or both.

PREVALENCE In a claims data study of AOM and recurrent AOM in the United States
between 2001 and 2011, the prevalence of recurrent AOM in children <6 years declined
from 17 to 11 percent after introduction of the 13-valent pneumococcal conjugate
vaccine [5]. In a prospective, longitudinal study in the postpneumococcal conjugate
vaccine era (2006-2016), the reported prevalence of recurrent AOM in children <2 years in
the Rochester community varied depending on how the diagnosis was made and who
made the diagnosis [4]. Among children seen by community clinicians, 27 percent were
diagnosed with recurrent AOM, whereas 14 percent of children seen by validated
otoscopists from a single practice met criteria for recurrent AOM, and only 6 percent when
tympanocentesis was employed for diagnosis of AOM.

OVERVIEW OF APPROACH

Interventions Specific interventions that may be used in the prevention of recurrent


AOM include [6-9]:

Identification and treatment of predisposing conditions (eg, exposure to tobacco


smoke)
Parental education about risks posed by day care settings
Breast feeding
Administration of influenza virus and/or pneumococcal conjugate vaccines
Antibiotic prophylaxis
Surgery (myringotomy and placement of tympanostomy tubes)

These interventions, discussed below, are typically approached in a stepwise fashion,


beginning with identification of underlying conditions, parental education and vaccine
administration, and then, if indicated, chemoprophylaxis and/or surgery [6,7].

Factors influencing choice Decisions regarding strategies for prevention of recurrent


AOM are made on a case-by-case basis. Factors to be considered in the decision include
[10]:

Age of the child Children younger than two years appear to receive the most
benefit from antibiotic prophylaxis.
Age at first episode Infants who have their first episode of AOM before six months
of age are at risk for severe and recurrent AOM [11], and early initiation of prevention
strategies may be warranted.
Time of year The child who has already had several episodes of AOM by late fall
(ie, November in the northern hemisphere) is likely to have many more before the end
of the winter, whereas the child who has recurrent episodes by late spring (ie, May in
the northern hemisphere) could be expected to have fewer additional infections
during the late spring and summer.
Attendance in large-group day care Children in this setting are likely to have more
respiratory infections, some of which will be accompanied by AOM.
Siblings Children with siblings younger than five years or who attend day care are
at increased risk for recurrent OM [12-15].
Family history The risk of AOM is increased in children whose other family
members have AOM.
The developmental status of the child, particularly language development. Children
with permanent hearing loss, suspected or confirmed speech or language delay or
disorder, developmental delay, autism spectrum disorder, or blindness or
uncorrectable visual impairment are at increased risk for speech, language, or
learning problems [16].
Underlying medical conditions that predispose to AOM (eg, cleft palate, immotile
cilia syndrome, immunoglobulin G [IgG] deficiency, Down syndrome).
The effects of recurrent AOM on the quality of life for the child and family.

Choice of intervention(s) When all factors are considered, the balance of risks and
benefits will favor less aggressive interventions for some children and more aggressive
interventions for others.

Less aggressive interventions (including no intervention) may be warranted for children


older than two years because the incidence of AOM declines after the second year of life.
Children between two and seven years with immature or defective immune function or
persistent Eustachian tube dysfunction often remain at increased risk for AOM after the
second year of life. Less aggressive interventions include treatment of predisposing
conditions, education, and provision of pneumococcal and influenza vaccines.
(See 'Treatment of predisposing conditions' below and 'Education' below
and 'Vaccines' below.)

We suggest more aggressive interventions (eg, antibiotic prophylaxis or tympanostomy


tube placement) for children with recurrent OM and one or more of the following:

Age <2 years (when optimal hearing is necessary for acquisition of language skills),
particularly in children with early onset disease
Multiple risk factors, especially if the risk factor cannot be modified (eg, time of year,
size of day care) (see "Acute otitis media in children: Epidemiology, microbiology,
clinical manifestations, and complications", section on 'Risk factors')
Underlying medical conditions that predispose to recurrent AOM
Comorbid conditions associated with developmental or language delays (the
conductive hearing loss associated with middle ear effusion may persist for weeks to
months after the acute signs of AOM have resolved and may add additional burden in
children with existing delays or deficits)

However, the ultimate decision about whether to use a more aggressive intervention and
which intervention to use is made on a case-by-case basis after discussion of the potential
benefits and risks with the caregivers.

The choice of antibiotic prophylaxis or tympanostomy tube placement is influenced by the


level of concern about antibiotic-resistant bacteria in the specific community, language
development, the risks of surgery and anesthesia, and the values and preferences of the
family. For children who have had frequent breakthrough episodes of AOM while receiving
antibiotic prophylaxis or who have multiple drug allergies and continue to warrant more
aggressive prevention strategies, we suggest tympanostomy tube placement.
(See 'Antibiotic prophylaxis' below and 'Tympanostomy tubes' below.)

The 2013 American Academy of Pediatrics (AAP) and American Academy of Family
Physicians (AAFP) clinical practice guideline for the diagnosis and management of AOM in
children 6 months through 12 years of age recommends that clinicians not prescribe
prophylactic antibiotics but "may offer" tympanostomy tubes to prevent recurrent AOM [8].
The 2013 AAP/AAFP guideline does not apply to children with underlying conditions that
may alter the natural course of AOM (eg, anatomic abnormalities, genetic conditions with
craniofacial abnormalities, immune deficiencies, or cochlear implants), whereas this topic
review does not make such exclusions.

The 2013 American Academy of Otolaryngology-Head and Neck Surgery Foundation


clinical practice guideline on tympanostomy tubes in children recommends against
tympanostomy tube insertion for children with recurrent AOM unless they have unilateral or
bilateral middle ear effusion at the time of assessment for placement of tympanostomy
tubes [16].

TREATMENT OF PREDISPOSING CONDITIONS The first step in the prevention of


recurrent AOM is identification, and treatment if warranted, of underlying conditions that
predispose the child to recurrent AOM. Such conditions include immune
deficiencies and/or anatomic abnormalities.

Children who have had suppurative infections at multiple sites, including recurrent AOM,
may have immunologic deficiencies. The most commonly identified immune abnormality in
children with recurrent AOM is an immunoglobulin G (IgG) subclass deficiency. Children
with recurrent AOM as their only manifestation of recurrent infection rarely have severe
immunologic abnormalities. However, hypogammaglobulinemia, granulocyte defects,
defective cell-mediated immunity, or HIV infection may present with recurrent AOM as part
of the spectrum of either increased infections or infections that resolve more slowly than
expected [17]. (See "Approach to the child with recurrent infections" and "IgG subclass
deficiency", section on 'Clinical manifestations' and "Primary humoral immunodeficiencies:
An overview", section on 'Presentation of humoral immunodeficiency'.)

Children with palatal clefts also are predisposed to the development of recurrent AOM.
This includes children with craniofacial abnormalities that are associated with submucous
palatal clefts, such as micrognathia and glossoptosis (seen in Robin sequence and similar
syndromes). (See "Congenital anomalies of the jaw, mouth, oral cavity, and pharynx",
section on 'Jaw anomalies'.)
EDUCATION Educating parents about ways to decrease exposure to risk factors (eg,
cigarette smoke) and increase exposure to protective factors (eg, breast feeding) is an
appropriate prevention strategy for all children with recurrent AOM [8]. Although the
effectiveness of parental education in preventing recurrent AOM has not been proven,
there is little risk of harm. The risk factors for AOM are discussed in detail separately.
(See "Acute otitis media in children: Epidemiology, microbiology, clinical manifestations,
and complications", section on 'Risk factors'.)

Specific risk/protective factors to be discussed include [1,7]:

Day care The fewer children in the day care group, the lower the exposure to
respiratory pathogens and risk for AOM.
Exposure to smoke Children exposed to cigarette smoke in the home have more
episodes of AOM than children in smoke-free homes; methods of home heating, such
as wood or coal burning stoves, also may be a risk factor. A suggested mechanism is
increased colonization with bacterial otopathogens leading to greater risk for
development of bacterial OM following viral respiratory tract infection. (See "Control of
secondhand smoke exposure".)
Breastfeeding Breastfeeding for at least three months protects against AOM
during the first year of life. Although this knowledge may not prevent recurrent AOM in
the index case, when family history suggests an increased risk of recurrent AOM,
breastfeeding may help prevent recurrent AOM in subsequent children.
Pacifiers The use of pacifiers after six months of age increases the risk of
recurrent AOM [18].

VACCINES The routine administration of pneumococcal conjugate vaccine and


influenza vaccine during infancy provides only a modest reduction in the frequency of AOM
but appears to have greater downstream benefits in reducing the development of recurrent
OM and the need for tympanostomy tube insertion [19]. These observations are consistent
with the hypothesis that prevention of early episodes has subsequent benefit in prevention
of recurrent and complex otitis media.

Pneumococcal conjugate vaccine We recommend that infants and children be


immunized with the 13-valent pneumococcal conjugate vaccine (PCV13) according to the
routine childhood immunization schedule at ages 2, 4, 6, and 12 months [8,20]. In a
randomized trial, children who received 7-valent pneumococcal conjugate vaccine (PCV7)
during infancy had a 34 percent lower risk of tympanostomy tube insertion at age two
through five years than those who received hepatitis B vaccine [19].

Randomized trials and systematic reviews have not found administration of pneumococcal
conjugate vaccines after the development of recurrent otitis media to be beneficial [21-24].
This is primarily because the importance of pneumococcal disease decreases as children
with recurrent otitis media get older. PCV13 has not been specifically studied in children
with recurrent otitis media. Despite the lack of evidence, we suggest PCV13 for children
younger than six years who continue to have recurrent episodes of AOM and have not
previously received PCV13. (See "Pneumococcal (Streptococcus pneumoniae) conjugate
vaccines in children".)

In randomized trials, administration of the PCV7 beginning at age two months was
associated with a modest reduction in AOM (6 to 8 percent) [25-27]. However, the efficacy
of prevention of culture-confirmed pneumococcal AOM caused by a vaccine serotype was
57 to 65 percent. In these and other randomized and observational studies, receipt of
PCV7 was associated with fewer medical visits for AOM and fewer tympanostomy tube
placements [19,25,26,28-33]. Several studies have noted an increase in AOM caused by
pneumococcal serotypes not included in the vaccine (ie, "replacement" serotypes)
[25,34,35].

The additional serotypes (particularly serotype 19A) in PCV13 provide additional protection
against AOM and recurrent AOM (table 1) [36]. In prospective surveillance from eight
childrens hospitals in the United States, the proportion of pneumococcal isolates from the
middle ear or mastoid of children that were PCV13 serotypes decreased from 50 percent
in 2011 to 29 percent in 2013 [37]; 19A isolates decreased from 34 to 10 percent. Initial
reports from Israel have also demonstrated declines in OM due to PCV13 vaccine
serotypes and overall otitis media [38]. Continued monitoring is necessary to characterize
the efficacy for prevention of vaccine serotype AOM and monitor for "replacement"
serotypes.

In countries where the pneumococcal conjugate vaccine is not part of the routine
immunization schedule, we suggest pneumococcal conjugate vaccine for infants and
young children at high-risk for recurrent AOM (ie, first episode of AOM at <6 months of
age, older siblings with severe and recurrent AOM). In a randomized trial, 96 infants with
AOM onset at <6 months of age were assigned to receive or not receive PCV7 [39].
Receipt of PCV7 was associated with a 26 percent reduction in AOM, a 36 percent
reduction in emergency department visits for suspected AOM, and a 50 percent reduction
in placement of ventilation tubes.

Pneumococcal polysaccharide vaccine For children older than two years who
continue to have recurrent episodes of AOM, we suggest administration of the 23-valent
pneumococcal polysaccharide (PPSV23) after completion of immunization with PCV13 to
provide coverage for as broad a range of pneumococcal serotypes as possible (table 1).
PPSV23 should be administered at least eight weeks after PCV13 [20].

A systematic review of randomized controlled trials evaluating pneumococcal vaccination


for AOM in children younger than 12 years found a moderate effect of pneumococcal
polysaccharide vaccine in the prevention of AOM in children older than 24 months who
had documented AOM before vaccination (relative risk 0.74, 95% CI 0.62 to 0.90) [21].
Influenza vaccine In the United States, annual influenza immunization is
recommended for all children 6 months [40]. In countries where universal influenza
immunization of infants is not routine, we suggest annual influenza vaccination for children
who had onset of AOM before six months of age or recurrent episodes of AOM during the
preceding winter [41]. (See "Seasonal influenza in children: Prevention with vaccines",
section on 'Target groups'.)

In a 2015 meta-analysis of five randomized trials including 4736 children age six months to
six years, influenza vaccine slightly reduced the risk of at least one episode of AOM over
six months of follow-up (risk difference [RD] 4 percent [95% CI 2 to 7]; risk ratio [RR] 0.80,
95% CI 0.67 to 0.96) [42]. In meta-analysis of two trials (1223 children), influenza vaccine
also appeared to reduce the number of antibiotic prescriptions (RD 15 percent, 95% CI [0-
30]; RR 0.70, 95% CI 0.59-0.83), but it is unclear whether this reduction was due to
influenza vaccine or increased frequency of "watchful waiting" for AOM to avoid overuse of
antibiotics. It is not surprising that influenza vaccine has only a modest impact on AOM
episodes, because infection with other respiratory viruses, such as respiratory syncytial
virus, parainfluenzae, and human metapneumovirus, appear to have a much greater
association with AOM. (See "Acute otitis media in children: Epidemiology, microbiology,
clinical manifestations, and complications", section on 'Viruses'.)

Influenza vaccination for children is discussed separately. (See "Seasonal influenza in


children: Prevention with vaccines".)

ANTIBIOTIC PROPHYLAXIS Prophylaxis with a modified dose of an antimicrobial


agent can be helpful in preventing recurrent AOM [43,44]. However, the protection afforded
by prophylaxis is not sustained after discontinuation [45].

Indications Antibiotic prophylaxis may be warranted for children who have had 3
distinct and well-documented episodes within six months or 4 episodes within 12 months
[3,46]. It also may be warranted for children with early onset of AOM (ie, at less than six
months of age) who have additional risk factors such as day care attendance, family
history of recurrent OM, or large number of siblings. However, decisions regarding the use
of antibiotic prophylaxis should be made on a case-by-case basis. The potential benefits
(20 to 50 percent fewer episodes) must be balanced with the risk of development of
nasopharyngeal colonization with antibiotic-resistant organisms [44,47]. Additional factors
that influence the decision to use antibiotic prophylaxis are discussed above. (See 'Factors
influencing choice' above.)

Potential benefits In a meta-analysis, of 14 randomized trials (1461 children)


comparing long-term antibiotics (>6 weeks) with placebo or no treatment for the prevention
of acute and chronic suppurative otitis media, antibiotic prophylaxis [44]:
Reduced the occurrence of any episode of AOM (37 versus 56 percent; pooled risk
ratio 0.65, 95% CI 0.53-0.79); approximately five children would need to be treated to
prevent one child from experiencing AOM while on treatment.
Reduced the number of episodes of AOM while on antibiotics from 3 to 1.5 per year
(incidence rate ratio 0.51, 95% CI 0.39-0.66).

The protection afforded by prophylaxis does not persist after discontinuation of


chemoprophylaxis. Many children in whom antibiotic prophylaxis is discontinued will have
recurrence of frequent AOM [45].

The findings of the meta-analysis must be interpreted with caution because the studies
that were included had different entry criteria, used different drugs for different durations,
and observed patients for various lengths of time. Most were conducted before the era of
widespread penicillin-resistant pneumococci and the recommendation for routine
immunization of infants with the pneumococcal conjugate vaccine.

Antibiotic prophylaxis compared with tubes In the only trial comparing antibiotic
prophylaxis and tympanostomy tube placement that excluded children with otitis media
with effusion, antibiotic prophylaxis was more effective [2]. In this trial, 264 children 7 to 35
months of age with recurrent AOM (3 episodes within six months or 4 episodes within 12
months) were randomly assigned to three groups, amoxicillin prophylaxis, myringotomy
and tympanostomy tube placement, or placebo, and followed for two years [2]. The
average rate of new episodes of AOM was decreased in the amoxicillin group compared
with the tympanostomy and placebo groups (0.6, 1.02, and 1.08 new episodes of AOM or
otorrhea per child per year, respectively).

Adverse effects Prolonged use of antibiotic prophylaxis for AOM may result in the
selection of resistant bacteria in the nasopharynx and subsequent respiratory tract
infection with resistant pathogens [44,47]. The treatment of AOM and other upper
respiratory infections caused by antibiotic-resistant organisms is discussed separately.
(See "Acute otitis media in children: Treatment", section on 'Initial antimicrobial
therapy' and "Acute bacterial rhinosinusitis in children: Microbiology and treatment",
section on 'Empiric antibiotic therapy'.)

Additional risks of prolonged antibiotic use include allergic reactions and diarrhea, as well
as Clostridium difficile-associated diarrhea (on rare occasions). (See "Clostridium difficile
infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Risk
factors'.)

Antibiotic choice and regimen When the decision is made to use antibiotic
prophylaxis, we typically use amoxicillin 40 mg/kg orally once per day unless the child has
a penicillin allergy (see "Penicillin allergy: Immediate reactions"). Sulfisoxazole
50 mg/kg orally once per day is an alternative. Cephalosporins usually are not used for
prophylaxis because they have a broader spectrum and are more expensive.
Antibiotic prophylaxis should be provided during the fall, winter, and early spring months,
when respiratory infections are most prevalent, but for no longer than six months [46]. In a
small randomized trial, administration every day was more effective than administration
only during upper respiratory infections [48].

Breakthrough AOM Breakthrough episodes of AOM in the child who is currently


on amoxicillin prophylaxis increases the likelihood of a beta-lactamase producing
nontypeable Haemophilus influenzae or a penicillin-resistant pneumococcus. Our initial
choice is amoxicillin-clavulanate 90 mg/kg per day of amoxicillin and 6.4 mg/kg per day of
clavulanate in two divided doses. Ceftriaxone 50 mg/kg intramuscularly once per day is an
alternative. A single dose of ceftriaxone may be sufficient, but often a two- or three-dose
regimen is necessary [49,50]. (See "Acute otitis media in children: Treatment", section on
'Initial antimicrobial therapy'.)

Follow-up During chemoprophylaxis, children should be examined whenever they have


signs or symptoms of AOM. (See "Acute otitis media in children: Diagnosis", section on
'Diagnosis'.)

Children without signs of AOM should be examined approximately every two months to
determine the presence and duration of middle ear effusion [7]. The management of
persistent middle ear effusion is discussed separately. (See "Otitis media with effusion
(serous otitis media) in children: Management", section on 'Overview of management'.)

SURGERY

Tympanostomy tubes Myringotomy with placement of tympanostomy tubes permits


drainage of the middle ear fluid, aeration of the middle ear space, and return of the middle
ear mucosa to normal. An abscess does not form because the tube allows drainage of
accumulated middle ear fluid. Nevertheless, recurrent infection may result in a mucositis
that is usually identified by systemic signs and/or otorrhea. (See "Overview of
tympanostomy tube placement, postoperative care, and complications in children", section
on 'Tube otorrhea' and "Tympanostomy tube otorrhea in children: Causes, prevention, and
management", section on 'Acute tympanostomy tube otorrhea'.)

The use of tympanostomy tubes in the prevention of recurrent AOM in otherwise healthy
children has increased as the popularity of chemoprophylaxis has decreased due to
concerns about antibiotic resistance among otopathogens. (See 'Adverse effects' above.)

Indications Tympanostomy tube placement may be warranted for children who have
had 3 distinct and well-documented episodes within six months or 4 episodes within 12
months. Decisions regarding the placement of tympanostomy tubes for recurrent AOM
must be individualized after consideration of the risks and benefits. (See 'Factors
influencing choice' above.)
We suggest tympanostomy tube placement for children who warrant more aggressive
prevention strategies and:

Have had breakthrough episodes of AOM while receiving prophylaxis, or


Have declined antibiotic prophylaxis (because of parental concerns), or
Have multiple drug allergies

Potential benefits A meta-analysis of five randomized trials of tympanostomy tubes


versus no surgery in children with AOM or otitis media with effusion (OME) showed a
mean absolute decrease in AOM incidence of 1 episode per child-year (95% CI 0.4-1.6)
[51]. When the analysis was limited to trials of children with recurrent AOM, the mean
absolute decrease in the incidence of AOM was 1.75 episodes per child-year (95% CI
-0.44-3.93).

A subsequent systematic review [52] that included only two trials (both of which included
children with OME) [53,54] found that insertion of tympanostomy tubes was associated
with a mean of 1.5 fewer episodes of AOM in the six months after surgery.

In a randomized trial published after the systematic review, 300 children (10 months to 2
years of age) with recurrent AOM (3 episodes in the previous six months) were randomly
assigned to tympanostomy tubes, tympanostomy tubes plus adenoidectomy, or neither
[55]. Treatment failure (defined as two episodes of AOM in two months, three episodes in
six months, or effusion for longer than two months) occurred in fewer patients in the
tympanostomy tube groups (21 and 16 percent in the tympanostomy tube and
tympanostomy tube/adenoidectomy groups, respectively, versus 34 percent in controls).
More children in the tympanostomy tube groups were AOM-free during the one year of
follow-up (48 and 49 percent in the tympanostomy tube and
tympanostomy tube/adenoidectomy groups, respectively, versus 34 percent in controls).
As discussed below, the combination of adenoidectomy and tympanostomy tubes did not
provide any advantage over tympanostomy tubes alone. (See 'Adenoidectomy or
adenotonsillectomy' below.)

Two trials included in the first meta-analysis compared tympanostomy tube placement with
chemoprophylaxis and placebo [2,56]. However, only one excluded children with OME [2].
This study, which is described in greater detail above, found antibiotic prophylaxis
with amoxicillin to be more effective than tympanostomy tube placement or placebo.
(See 'Antibiotic prophylaxis compared with tubes' above.)

Adverse effects Myringotomy and placement of tympanostomy tubes are surgical


procedures and parents should be informed about the potential adverse events associated
with anesthesia and surgery. Complications and sequelae of tympanostomy tubes include
otorrhea, persistent perforation of the tympanic membrane, tympanosclerosis, focal
atrophy of the tympanic membrane, and cholesteatoma. (See "Overview of tympanostomy
tube placement, postoperative care, and complications in children", section on
'Complications and sequelae'.)

Adenoidectomy or adenotonsillectomy When the decision is made to proceed with a


first set of tympanostomy tubes, concurrent adenoidectomy is indicated only for patients
with moderate to severe nasal obstruction [1]. (See "Tonsillectomy and/or adenoidectomy
in children: Indications and contraindications", section on 'Nasal obstruction'.)

Adenoidectomy, with or without tonsillectomy, does not appear to be an effective primary


preventive measure for children with recurrent AOM [55,57-59]. Two randomized clinical
trials run in parallel failed to demonstrate a substantial effect of adenoidectomy or
adenotonsillectomy on the occurrence of AOM in patients 3 to 15 years of age with
recurrent otitis media and no previous history of tympanostomy tubes, whether or not they
had evidence of enlarged tonsils or adenoids [57].

The relative merits of adenoidectomy at the time of tympanostomy tube placement in


children with recurrent AOM (more than three episodes in the past six months) or chronic
otitis media with effusion were evaluated in a prospective trial [60]. A total of 217 children
with no previous surgery (aged 12 to 48 months) were randomly assigned to
adenoidectomy with insertion of tympanostomy tubes or insertion of tympanostomy tubes
alone. There was no difference in the incidence of subsequent AOM between the two
groups [60].

In contrast, adenoidectomy with or without tonsillectomy may be helpful in reducing the


number of episodes of AOM in children who have recurrences after an initial placement of
tympanostomy tubes [61]. A retrospective study suggested that adenoidectomy or
adenoidectomy plus tonsillectomy at the time of tube reinsertion substantially reduced the
incidence of subsequent hospitalizations and repeat tympanostomy tube insertion in
patients 2 years of age [62]. (See "Tonsillectomy and/or adenoidectomy in children:
Indications and contraindications", section on 'Otitis media'.)

OTHER INTERVENTIONS

Xylitol We do not suggest the use of xylitol to prevent recurrent AOM in children.
Although there is some evidence to suggest that xylitol may be beneficial, additional
information is necessary before it can be routinely recommended [63].

Xylitol is a five-carbon sugar alcohol that is used in place of sucrose as a sweetener. It has
been shown to prevent dental caries by inhibiting the growth of Streptococcus mutans and
has been studied as a means of preventing AOM in children attending day care [64-66].

In a 2016 meta-analysis of three randomized trials [67-69], two to three months of xylitol
chewing gum, syrup, or lozenges prevented recurrent AOM among healthy children (mean
age two to five years) attending day care (risk ratio 0.75, 95% CI 0.65-0.88) [66]. In
individual studies, administration of xylitol five times per day was effective [67,68], but
three times per day was not [69]. In a separate randomized trial, xylitol syrup administered
only during respiratory infections did not prevent AOM among children attending day care
[70].

Although the results of the meta-analysis are promising, it has several limitations. The
mean ages in the study populations were older than the age of peak incidence of AOM (2
to 5 years versus 6 to 18 months). In addition, it is not clear that the study conditions (eg,
administration of xylitol five times per day) could be replicated in "the real world." A
subsequent randomized trial in children six months to five years (mean age approximately
22 months) found no benefit of a three-times-daily dosing regimen of xylitol in preventing
recurrent otitis media [71].

The optimal dose, dosing regimen, long-term benefits, and full range of adverse effects
must be determined before xylitol can be recommended to prevent AOM [63].

Antiadhesive oligosaccharide Administration of oligosaccharides may be helpful in


the prevention of infection by inhibiting the binding of bacteria to epithelial cells [72-74]. In
an animal study, intratracheal administration of antiadhesive oligosaccharides was
effective in decreasing pneumococcal load and subsequent bacteremia [75]. However, in a
randomized controlled trial, nasopharyngeal administration of oligosaccharides to children
for three months did not affect nasopharyngeal carriage of S. pneumoniae, H. influenzae,
or Moraxella catarrhalis or prevent AOM [76]. We do not suggest the administration of
oligosaccharides to prevent recurrent AOM in children.

Probiotics We do not suggest the administration of probiotics to prevent recurrent AOM


in children. In theory, administration of probiotics after treatment of AOM recolonizes the
nasopharynx with bacteria that can hinder the growth of pathogenic bacteria. However,
studies evaluating probiotic for the prevention of recurrent AOM have inconsistent results.

Two randomized trials, each including >200 children, found no benefit of oral probiotics in
the prevention of recurrent AOM [77,78]. In another randomized trial, more children who
received alpha-streptococcal nasal spray than placebo nasal spray remained AOM-free for
three months (42 versus 22 percent) [79]. Alpha-streptococcal nasal spray is not
commercially available.

Other complementary therapies Nearly one-half of families of children with recurrent


AOM may try complementary, holistic, or integrative therapies (eg, herbal remedies,
homeopathy, nutritional supplements, such as zinc) to prevent recurrent AOM [80].
Although some of these interventions have been evaluated in clinical trials, methodologic
limitations preclude definitive conclusions about their safety or efficacy [8,81,82].

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Acute otitis media and otitis media with effusion in children".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

Basics topic (see "Patient education: Ear tubes (The Basics)")


Beyond the Basics topic (see "Patient education: Ear infections (otitis media) in
children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Recurrent acute otitis media (AOM) is defined as 3 distinct and well-documented


episodes within six months or 4 episodes within 12 months. Infants who have their
first episode of AOM before six months of age or who have siblings with severe and
recurrent AOM are at risk for severe and recurrent AOM. (See 'Definitions' above.)
Prevention strategies include identification and treatment of underlying conditions
that predispose to recurrent AOM, parental education about the risk factors for AOM,
vaccine administration, chemoprophylaxis, and tympanostomy tube placement.
(See 'Interventions' above.)
Factors that influence the choice of prevention strategy include the age of the child,
the age at first episode of AOM, the time of year, day care attendance, family history,
cognitive and language status, underlying conditions that predispose to AOM, and the
effects of recurrent AOM on the quality of life for the child and family. (See 'Factors
influencing choice' above.)
Treatment of predisposing conditions and parental education are reasonable
strategies for all children with recurrent AOM. (See 'Treatment of predisposing
conditions' above and 'Education' above.)
We recommend administration of the pneumococcal conjugate vaccine (PCV) and
annual influenza vaccine according to the routine childhood immunization schedule
(Grade 1A). We suggest that children with recurrent AOM who are between two and
six years of age and have not received any doses of the 13-valent PCV (PCV13),
receive a dose of PCV13 (Grade 2C). We also suggest that children older than two
years of age with recurrent AOM receive a dose of the 23-valent pneumococcal
conjugate vaccine at least eight weeks after PCV13 (Grade 2C).
(See 'Vaccines' above and "Seasonal influenza in children: Prevention with vaccines",
section on 'Target groups' and "Pneumococcal (Streptococcus pneumoniae)
conjugate vaccines in children", section on 'Otitis media'.)
We suggest antibiotic prophylaxis or tympanostomy tube placement for children who
are younger than two years of age, have multiple risk factors for recurrent AOM, have
underlying medical conditions that predispose to AOM, or have known or suspected
developmental or language delays (Grade 2B). However, the ultimate decision about
whether to use one of these more aggressive interventions and which intervention to
use is made on a case-by-case basis after discussion of the potential benefits and
risks with the caregivers. (See 'Choice of intervention(s)' above.)
When the decision is made to use antibiotic prophylaxis, we typically
use amoxicillin 40 mg/kg orally once per day. Sulfisoxazole 50 mg/kg orally once per
day is an alternative. Antibiotic prophylaxis should be provided every day during the
fall, winter, and early spring months. Children receiving chemoprophylaxis should be
examined approximately every two months to determine the presence and duration of
middle ear effusion. (See 'Antibiotic prophylaxis' above.)
Tympanostomy tube placement is an alternative to antibiotic prophylaxis for children
who warrant more aggressive prevention strategies and an option for those who have
had breakthrough episodes of AOM while receiving antibiotic prophylaxis.
(See 'Choice of intervention(s)' above and 'Tympanostomy tubes' above.)
Adenoidectomy is not an effective primary preventive measure for children with
recurrent AOM but may be beneficial in those who continue to have recurrent AOM
after extrusion of tubes and are undergoing repeat tympanostomy tube placement.
(See 'Adenoidectomy or adenotonsillectomy' above.)
We do not suggest xylitol, antiadhesive oligosaccharide, or probiotics for the
prevention of recurrent AOM in children (Grade 2C). (See 'Other
interventions' above.)

FARINGOAMIGDALITIS

Evaluation of sore throat in children

Author:
Gary R Fleisher, MD
Section Editors:
George A Woodward, MD
Jan E Drutz, MD
Deputy Editor:
James F Wiley, II, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Aug 14, 2015.

INTRODUCTION Sore throat refers to any painful sensation localized to the pharynx or
surrounding anatomy. The developmental ability of young children to identify and define
their symptoms varies and the physician must pay careful attention to the patient and the
caretaker in order to clarify the exact nature of the complaint.

Sore throat can be the symptom of a disease process that does not directly affect the
pharynx. Occasionally, young patients with dysphagia that results from disease in the area
of the esophagus or with difficulty swallowing because of a neuromuscular disorder may
verbalize these sensations as a sore throat or their symptoms may be interpreted by a
caretaker as a sore throat.

This topic will review conditions that can cause the symptom of sore throat. The discussion
will include pertinent features of the history and physical examination and an algorithmic
approach to common and life threatening conditions. The approach to the child with
infectious pharyngitis is discussed in more detail elsewhere. (See "Group A streptococcal
tonsillopharyngitis in children and adolescents: Clinical features and diagnosis".)

CAUSES

Life-threatening conditions

Epiglottitis The incidence of epiglottitis, a well-appreciated cause of life-threatening


upper airway infection, has declined significantly since the introduction of vaccination
against Haemophilus influenzae type b [1]. This disease manifests with a toxic
appearance, high fever, stridor, and drooling [2,3]. Sore throat occurs in many cases, but is
only rarely the primary complaint. (See "Epiglottitis (supraglottitis): Clinical features and
diagnosis".)

Retropharyngeal abscess Retropharyngeal abscesses can cause sore throat and


usually occur in children less than four years of age [4]. Other complaints include neck
pain and fever. There may be difficulty swallowing and respiratory distress. The posterior
location of the abscess makes it difficult to visualize on physical examination. Imaging is
often required to confirm the diagnosis. (See "Retropharyngeal infections in children".)
Lateral pharyngeal abscesses Lateral pharyngeal abscesses produce symptoms
similar to retropharyngeal infections but occur less often [5]. High fever is common. Other
signs include trismus and swelling below the mandible.

Peritonsillar abscess A peritonsillar abscess may complicate a previously diagnosed


infectious pharyngitis or may be the initial source of a child's discomfort [6]. This disease is
most common in older children and adolescents. The diagnosis is evident from visual
inspection, augmented occasionally by careful palpation. The abscess produces a bulge in
the posterior aspect of the soft palate, deviates the uvula to the contralateral side of the
pharynx, and has a fluctuant quality on palpation. (See "Retropharyngeal infections in
children".)

Infectious mononucleosis Infectious mononucleosis can rarely cause airway


obstruction from severe tonsillar hypertrophy.

Diphtheria Diphtheria is a life-threatening but seldom encountered cause of infectious


pharyngitis, characterized by a thick pharyngeal membrane and marked cervical
adenopathy. (See "Epidemiology and pathophysiology of diphtheria".)

Lemierre syndrome This unusual infection is caused by Fusobacterium necrophorum


[7] or mixed anaerobic flora and is associated with jugular venous thrombophlebitis and
the dissemination of infection by septic emboli. Both children and adults with Lemierres
syndrome almost always have pharyngitis at presentation [8,9]. It should be considered in
the ill-appearing patient with severe pharyngitis [10,11]. (See "Retropharyngeal infections
in children", section on 'Complications'.)

Common conditions

Viral pharyngitis Infection is the most common cause of sore throat and the etiologic
agents are usually respiratory viruses, including adenoviruses, coxsackie A viruses,
influenza, or parainfluenza virus (table 1). Some of these viruses produce easily
identifiable syndromes, including herpangina or hand, foot, and mouth disease (coxsackie
virus) and pharyngoconjunctival fever (adenovirus). Herpangina is common in infants and
young children and decreases in frequency as age increases. Herpes simplex virus usually
causes stomatitis (discussed below). However, it may cause pharyngitis in the
immunocompromised child, and rarely in the immunocompetent child. (See "Clinical
manifestations and diagnosis of enterovirus and parechovirus
infections" and "Epidemiology and clinical manifestations of adenovirus infection".)

Streptococcal pharyngitis Viral etiologies are closely followed in frequency by group A


streptococcus (Streptococcus pyogenes), which is the most frequent bacterial cause of
infectious pharyngitis [12,13]. In the winter months during streptococcal outbreaks, as
many as 30 percent of episodes of pharyngitis may be caused by S. pyogenes.
(See "Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical
features and diagnosis", section on 'Epidemiology'.)
Infectious mononucleosis The only other common infectious agent in pharyngitis is
the Epstein-Barr virus (EBV), which causes infectious mononucleosis and affects
adolescents most frequently. Rarely, infectious mononucleosis can cause life threatening
airway obstruction from tonsillar hypertrophy. (See "Clinical manifestations and treatment
of Epstein-Barr virus infection".)

An additional consideration in adolescents with an infectious mononucleosis-like syndrome


is human immunodeficiency virus (HIV). (See "The natural history and clinical features of
HIV infection in adults and adolescents".)

Other conditions

Unusual infections Other organisms produce pharyngitis only rarely; these


include Neisseria gonorrhoeae, Corynebacterium diphtheriae, Francisella tularensis,
and anaerobic bacteria.
N. gonorrhoeae may cause inflammation and exudate but more often remains
quiescent and is diagnosed only by culture [14]. (See "Clinical manifestations
and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents".)
Oropharyngeal tularemia is rare and should be entertained only in endemic
areas among children who have an exudative pharyngitis that cannot be
categorized by standard diagnostic testing and/or persists despite antibiotic
therapy. (See "Epidemiology, microbiology, and pathogenesis of
tularemia" and "Clinical manifestations, diagnosis, and treatment of tularemia".)
Other organisms, including group C and G streptococci, Arcanobacterium
hemolyticum, Mycoplasma pneumoniae, and Chlamydia pneumoniae [15], have
been implicated as agents of pharyngitis in adolescents and adults, but in
childhood their roles remain unproven and their frequency is unknown.
Irritative pharyngitis Drying of the pharynx may irritate the mucosa, leading to a
complaint of sore throat. This condition occurs most commonly during the winter
months, particularly after a night's sleep in a house with forced hot-air heating.
Foreign body Occasionally, a foreign object such as a fish bone may become
embedded in the pharynx. (See "Airway foreign bodies in children", section on
'Presentation'.)
Herpetic stomatitis Stomatitis caused by herpes simplex usually is confined to
the anterior buccal mucosa but may extend to the tonsillar pillars. In these more
extensive cases, the child may complain of a sore throat. (See "Clinical
manifestations and diagnosis of herpes simplex virus type 1 infection".)
Systemic inflammatory conditions Examples include:
Kawasaki disease is characterized by high fever along with at least four of the
five following findings [16]: conjunctivitis, mucositis, peripheral
erythema and/or edema, truncal rash, cervical adenopathy. Kawasaki disease is
discussed in detail separately. (See "Kawasaki disease: Epidemiology and
etiology".)
Stevens-Johnson syndrome is a disease of unknown etiology, but presumed to
be immune mediated, which is characterized by vesicular and ulcerative lesions
of the mucosa, including the pharynx, genitalia, and conjunctivae. Additionally,
children with this condition may have a diffuse rash, often consisting of target
lesions or vesicles and bullae. Usually self-limited, occasional cases may lead to
dehydration or progress to involve the pulmonary system. Rarely, Stevens-
Johnson syndrome may be fatal. (See "Stevens-Johnson syndrome and toxic
epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)
Behets syndrome is a more chronic systemic inflammatory disease that may
involve the oral cavity. It is uncommon in children. (See "Clinical manifestations
and diagnosis of Behets syndrome".)
Periodic fever with aphthous stomatitis, pharyngitis and adenitis (PFAPA
syndrome) is a cyclical inflammatory disease of unknown etiology. Episodes
occur primarily in school age children approximately every four weeks. Mean
duration of illness ranges from four to eight years. (See "Periodic fever with
aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome)", section on
'Clinical manifestations' and "Periodic fever with aphthous stomatitis, pharyngitis
and adenitis (PFAPA syndrome)", section on 'Natural history'.)
Chemical exposure Certain ingestions, such as paraquat and various alkalis,
may cause a chemical injury to the mucosa of the pharynx. Usually these findings
occur in the setting of a known ingestion and are accompanied by lesions of the oral
mucosa. (See "Caustic esophageal injury in children".)
Referred pain Occasionally, pain from inflammation of extrapharyngeal structures
is described as arising in the pharynx. Examples include dental abscesses, cervical
adenitis, and otitis media.
Psychogenic pharyngitis Some children who complain of a sore throat have no
organic explanation for their complaint identified after a thorough history and physical
examination and a throat culture. In these cases, the physician should consider the
possibility of anxiety, at times associated with frequent or difficult (globus hystericus)
swallowing. (See "Globus sensation".)
Immunosuppressed host Immunosuppressed hosts may develop pharyngitis
from any of the previously discussed causes. In addition, these patients exhibit a
particular susceptibility to infections with fungal organisms, such as Candida albicans.
(See "Candida infections in children: An overview", section on 'Oropharyngeal
candidiasis'.)

HISTORY Key historical variables that may assist in the diagnosis of a specific cause of
sore throat include respiratory distress, fever, fatigue, and the rapidity of the onset of
symptoms.

Sore throat and respiratory distress The combination of sore throat and
respiratory distress suggests conditions in or near the pharynx that are producing an
obstruction, including epiglottitis, retropharyngeal or lateral pharyngeal abscess,
peritonsillar abscess, massive tonsillar hypertrophy secondary to infectious
mononucleosis, and rarely diphtheria.
Fever Fever points to one of the many infectious causes (table 1) but may also
occur with inflammatory conditions.
Fatigue Fatigue, particularly when prolonged, characterizes infectious
mononucleosis.
Abrupt onset Among the diseases causing pharyngitis, epiglottitis has a
particularly abrupt onset, in a matter of hours, while infectious mononucleosis
manifests over a period of days or weeks.

Other factors in the history that may be important in selected cases include
immunocompromising conditions, immunizations, travel, sexual activity, and frequent
recurrences. The patient with a compromised immune system is susceptible to a number
of infections, including Candida albicans. Diphtheria rarely merits consideration, except in
unimmunized children and those from underdeveloped nations. With a history of oral
sexual activity, pharyngeal gonorrhea may be a concern. Frequently recurring episodes of
pharyngitis are usually secondary to respiratory viruses and/or GABHS infections but may
indicate PFAPA.

PHYSICAL EXAMINATION To a large degree, the evaluation of the child with a


complaint of sore throat hinges on a careful physical examination, particularly of the
pharynx.

Stridor, drooling, or respiratory distress indicate airway obstruction and may be


present in the occasional patients with conditions such as epiglottitis or
retropharyngeal abscess.
An inflamed eardrum suggests pain from a non-oropharyngeal site and swelling
around a tooth indicates a likely dental abscess.
The appearance of vesicles on the buccal mucosa anterior to the tonsillar pillars
points to a herpetic stomatitis or noninfectious syndromes, such as Behets or
Stevens-Johnson syndrome (erythema multiforme). (See "Stevens-Johnson
syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and
diagnosis" and "Clinical manifestations and diagnosis of Behets syndrome".)
Generalized inflammation of the oral mucosa, in a persistently febrile child, suggests
Kawasaki disease. (See "Kawasaki disease: Epidemiology and etiology".)
A foreign body, such as a fish bone, may uncommonly become lodged in the
mucosal folds of the tonsils or pharynx; usually, the history suggests the diagnosis,
but an unanticipated sighting may occur in the younger child.
Significant asymmetry of the tonsils indicates a peritonsillar cellulitis or, if extensive,
an abscess. Clinically, the diagnosis of an abscess is reserved for the tonsil that
protrudes beyond the midline, causing the uvula to deviate to the uninvolved side.
Infectious pharyngitis evokes a spectrum of inflammatory responses that range from
minimal injection of the mucosa to beefy erythema with exudation and edema formation.
Erythema and exudate, which may be secondary to either viral or bacterial pathogens, will
be present in the majority of patients. (See "Group A streptococcal tonsillopharyngitis in
children and adolescents: Clinical features and diagnosis", section on 'Differential
diagnosis'.) Several specific findings are useful in pinpointing an etiologic agent.

Viral pharyngitis that results from Coxsackie virus will be self-evident in a few cases
on the basis of vesicular formation in the posterior pharynx alone (herpangina) or in
combination with involvement of the extremities (hand, foot, and mouth disease).
(See "Clinical manifestations and diagnosis of enterovirus and parechovirus
infections" and "Clinical manifestations and diagnosis of herpes simplex virus type 1
infection".)
The typical appearance of streptococcal pharyngitis includes fever, exudative
pharyngitis, palatal petechiae, and swollen anterior cervical lymph nodes. Strategies
for improving the clinical diagnosis of streptococcal pharyngitis, including a scoring
system, are discussed elsewhere. In general, scoring systems do not replace the
need for rapid streptococcal antigen testing.
Diphtheria causes a particularly thick exudate (diphtheritic membrane), often in
association with tremendous enlargement of the cervical lymph nodes ("bull neck").
(See "Epidemiology and pathophysiology of diphtheria".)
In infectious mononucleosis, the examination may show large, mildly tender
posterior cervical lymph nodes, diffuse lymphadenopathy outside the cervical region,
and splenomegaly or, less commonly, hepatomegaly. Although some young children
with EBV infection do not always develop this typical pattern of signs and symptoms,
many will have fever, pharyngitis, and cervical lymphadenopathy [17]. (See "Clinical
manifestations and treatment of Epstein-Barr virus infection".)

ANCILLARY STUDIES The history and physical examination will often suffice for
diagnosis. Ancillary studies that may be useful include testing for streptococcal disease by
antigen detection or culture and a heterophile test and white blood cell count with
differential for infectious mononucleosis [18]. (See "Group A streptococcal
tonsillopharyngitis in children and adolescents: Clinical features and diagnosis", section on
'Diagnosis'.) Children can have symptomatic primary EBV infection without the production
of heterophile antibodies and EBV specific serology may be necessary to make the
diagnosis [19]. (See "Clinical manifestations and treatment of Epstein-Barr virus
infection".)

A soft-tissue radiographic examination of the lateral neck may be useful in the child who is
ill appearing, has significant difficulty swallowing, or who will not move his neck. An
abnormal epiglottis and a retropharyngeal abscess can be identified on this view (image
1).
In order to diagnose a retropharyngeal abscess, the radiograph should be a true lateral,
and the child must keep the neck in extension during inspiration to avoid a false thickening
of the retropharyngeal space. Findings consistent with a retropharyngeal abscess include
a prevertebral space that is increased in depth compared with the anteroposterior
measurement of the adjacent vertebral body, or a retropharyngeal space that is greater
than 7 mm at C2 or 14 mm at C6 (image 2). Another method for interpreting the width of
the prevertebral space is that it should normally measure no more than half the thickness
of the vertebral body from C1-C4, or the full thickness from C5-C7. If the diagnosis
remains uncertain despite adequate radiographs, a computed tomography (CT) scan
should be obtained. A CT scan will confirm the diagnosis of a lateral abscess (image 3).

If radiographs are normal and a lateral pharyngeal abscess is suspected on the basis of
torticollis or asymmetrically enlarged anterior cervical lymph nodes, then a CT scan is
indicated.

ALGORITHMIC APPROACH The tendency of most clinicians is to assume that one of


the common organisms is the cause of pharyngitis in the child with a sore throat. Before
settling on infectious pharyngitis, however, the clinician should first at least briefly consider
several more serious disorders (algorithm 1).

Acutely ill patients Conditions that have immediate life-threatening potential include
epiglottitis, retropharyngeal and lateral pharyngeal abscesses, peritonsillar abscess,
severe tonsillar hypertrophy (usually as an exaggerated manifestation of infectious
mononucleosis), diphtheria, and Lemierre's syndrome.

Generally, stridor and signs of respiratory distress accompany the complaint of sore throat
in epiglottitis and retropharyngeal abscess. Drooling occurs commonly in children with
these two conditions. Patients with epiglottitis, peritonsillar abscess, or severe infectious
tonsillar hypertrophy often experience a change in their voice. In cases of epiglottitis or
retropharyngeal abscess that are not clinically obvious, a lateral neck radiograph, obtained
under appropriate supervision, is confirmatory.

Peritonsillar abscess and tonsillar hypertrophy are diagnosed by visual examination of the
pharynx. Diphtheria, which produces a thick pharyngeal exudate and markedly enlarged
cervical lymph nodes, is rarely a consideration except in unimmunized children, particularly
those from underdeveloped nations.

Lemierre's syndrome is a complication of mixed anaerobic pharyngeal infection leading to


sepsis. The child appears toxic, has high fever, neck pain, often has asymmetrically
enlarged anterior cervical lymph nodes, and may be hypotensive.

The next phase of the evaluation of the child with a complaint of sore throat hinges on a
careful physical examination, particularly of the pharynx. The appearance of vesicles on
the buccal mucosa anterior to the tonsillar pillars points to a herpetic stomatitis or
noninfectious syndromes, such as Behets or Stevens-Johnson syndrome (erythema
multiforme), and generalized inflammation of the oral mucosa in a persistently febrile child
suggests Kawasaki disease.

Uncommonly, a small, pointed foreign body, perhaps a fish bone, becomes lodged in the
mucosal folds of the tonsils or pharynx; usually, the history suggests the diagnosis, but an
unanticipated sighting may occur in the younger child. Significant asymmetry of the tonsils
indicates a peritonsillar cellulitis or, if extensive, an abscess. Clinically, the diagnosis of an
abscess is reserved for the tonsil that protrudes beyond the midline, causing the uvula to
deviate to the uninvolved side.

A pharynx that is not inflamed suggests a source of referred pain or irritative pharyngitis.
Sources of referred pain (otitis media, dental abscess, and cervical adenitis) usually are
identified during the examination. Irritative pharyngitis, seen most commonly during the
winter among older children who live in homes with forced hot-air heating, produces
minimal or no pharyngeal inflammation. It often is transient, appearing on arising and
resolving by midday.

Suspected infectious pharyngitis Patients who do not have one of the life threatening
conditions discussed above and do not have another easily identifiable cause of sore
throat (eg, foreign body) are likely to have infectious pharyngitis.

Infectious pharyngitis evokes a spectrum of inflammatory responses that range from


minimal injection of the mucosa to beefy erythema with exudation and edema formation
(algorithm 2). The three relatively common causes are streptococci, respiratory viruses,
and infectious mononucleosis. In a few cases, a viral pharyngitis that results from
Coxsackie virus infection will be evident on the basis of vesicular formation in the posterior
pharynx alone (herpangina) or in combination with involvement of the extremities (hand,
foot, and mouth disease). Such patients require only symptomatic therapy.

For patients without pharyngeal vesicles who have significant symptoms with pharyngeal
erythema and/or exudate, it is prudent to obtain a rapid test for group A streptococcus,
followed by a throat culture if the rapid test is negative. Back up culture for a rapid antigen
diagnostic test is recommended. However back up testing (either culture or rapid DNA
probe) may not be necessary in older adolescents similar to the approach in adult patients.
(See "Evaluation of acute pharyngitis in adults", section on 'Rapid antigen detection test'.)
In settings where a rapid test is not routinely performed or available, a throat culture for
group A streptococcus should be obtained.

In the rare child with an unusual history, the physician must pursue diagnoses such as
gonococcal pharyngitis (sexual abuse, oral sex) or diphtheria (immigration from an
underdeveloped country, lack of immunization). If no diagnosis has yet been made in a
child who has persistent sore throat and fever, infectious mononucleosis merits
consideration even in the absence of lymphadenopathy and splenomegaly. (See "Clinical
manifestations and treatment of Epstein-Barr virus infection".)
Some authorities find it acceptable not to perform either culture or rapid antigen diagnostic
testing if all clinical features point towards a viral etiology (no exudate, no palatal
petechiae, no cervical lymphadenopathy, URI symptoms present) in a developed country
with a low risk of non-suppurative post-streptococcal complications, such as rheumatic
fever [20].

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Streptococcal tonsillopharyngitis".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, The Basics and Beyond the Basics. The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)

Basics topics (see "Patient education: Sore throat in children (The


Basics)" and "Patient education: Strep throat in children (The Basics)")
Beyond the Basics topic (see "Patient education: Sore throat in children (Beyond the
Basics)")

SUMMARY

The approach to the evaluation of sore throat is summarized in the algorithms


(algorithm 1 and algorithm 2). (See 'Algorithmic approach' above.)
The table summarizes the causes of sore throat (table 1). (See 'Causes' above.)
reatment and prevention of streptococcal tonsillopharyngitis

Author:
Michael E Pichichero, MD
Section Editors:
Daniel J Sexton, MD
Morven S Edwards, MD
Deputy Editor:
Elinor L Baron, MD, DTMH

Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Feb 16, 2017.

INTRODUCTION Tonsillopharyngitis due to Streptococcus pyogenes, also known as


group A Streptococcus (GAS) (table 1 and table 2), presents with abrupt onset of sore
throat, tonsillar exudate, tender cervical adenopathy, and fever, followed by spontaneous
resolution within two to five days. Patients with sore throat lasting longer than one week
usually do not have GAS tonsillopharyngitis.

Issues related to treatment and prevention of group A streptococcal tonsillopharyngitis will


be reviewed here [1]. A general approach to patients with pharyngitis and the factors
responsible for antibiotic failure are discussed separately. (See "Evaluation of acute
pharyngitis in adults" and "Group A streptococcal tonsillopharyngitis in children and
adolescents: Clinical features and diagnosis" and "Antibiotic failure in the treatment of
streptococcal tonsillopharyngitis".)

GOALS OF THERAPY Goals of antimicrobial therapy for eradication of group


A Streptococcus (GAS) from the pharynx in the setting of acute streptococcal pharyngitis
include:

Reducing duration and severity of clinical signs and symptoms, including


suppurative complications
Reducing incidence of nonsuppurative complications (eg, acute rheumatic fever)
Reducing transmission to close contacts by reducing infectivity

Considerations of treatment include ease of antibiotic administration and limited expense


with as few adverse effects as possible [2-4].

Reducing clinical symptoms Antibiotic therapy is most beneficial for hastening


resolution of symptoms if instituted within the first two days of illness [5-9]. Antibiotic
therapy is also beneficial for reducing suppurative complications (such as peritonsillar
abscess, cervical lymphadenitis, and mastoiditis), although the severity of signs and
symptoms of GAS pharyngitis does not predict the likelihood of complications [10].
Additional issues related to antibiotic therapy for reducing clinical symptoms are discussed
further below. (See 'Timing of therapy' below.)

Reducing nonsuppurative complications Antibiotic therapy is primarily helpful for


reducing the incidence of acute rheumatic fever as a nonsuppurative complication of GAS
pharyngitis. The role of antibiotic therapy in decreasing the nonsuppurative complications
of glomerulonephritis and pediatric autoimmune neuropsychiatric disorder associated with
group A streptococci (PANDAS) syndrome is not clear [11].

Acute rheumatic fever Although symptoms of GAS pharyngitis resolve without


antibiotic therapy, persistence of the organism in the upper respiratory tract elicits an
immune response that can set the stage for subsequent risk of acute rheumatic fever
(ARF) if the strain is rheumatogenic and the host is genetically predisposed. (See "Acute
rheumatic fever: Epidemiology and pathogenesis" and "Acute rheumatic fever: Clinical
manifestations and diagnosis".)

The efficacy of penicillin for primary prevention of ARF was established in the early 1950s
when military recruits with GAS tonsillopharyngitis received injectable penicillin G mixed in
peanut oil or sesame oil with 2% aluminum monostearate [12,13]. GAS eradication and
ARF primary prevention were optimized with injection schedules that provided at least 9 to
11 days of penicillin.

Subsequently, evaluation of GAS tonsillopharyngitis therapies has been based upon GAS
eradication from the upper respiratory tract; it is assumed that such eradication is an
adequate surrogate marker for efficacy in primary prevention of rheumatic fever. Antibiotic
therapy can be helpful for prevention of rheumatic fever if initiated up to nine days
following onset of symptoms [12].

Glomerulonephritis Children younger than seven years of age appear to be at


greatest risk of poststreptococcal glomerulonephritis. Although antibiotic therapy has
efficacy for primary prevention of acute rheumatic fever, the role of antibiotics in the setting
of GAS tonsillopharyngitis for prevention of poststreptococcal glomerulonephritis is not
certain. (See "Differential diagnosis and evaluation of glomerular disease", section on
'Hematuria following upper respiratory infection'.)

PANDAS syndrome Pediatric autoimmune neuropsychiatric disorder associated with


group A streptococci is discussed separately. It is not clear whether antibiotic therapy for
GAS pharyngitis reduces the incidence of this syndrome. (See "Complications of
streptococcal tonsillopharyngitis", section on 'PANDAS syndrome'.)

Reducing transmission The rate of GAS transmission from an infectious case to close
contacts (such as a family or school setting) is approximately 35 percent. Antibiotic
treatment does have a role for preventing transmission of GAS. In one study including 47
children with pharyngitis and positive throat culture for GAS, subsequent throat culture
after 24 hours of treatment with penicillin was negative in about 80 percent of cases [14].
In another study including 111 children with positive rapid antigen detection test (RADT)
treated with amoxicillin (50 mg/kg) by 5:00 pm on day 1, negative follow-up RADT the
following morning was observed in 91 percent of patients [15].

Data on the duration of contagion for alternative antibiotics are not available. In untreated
patients, GAS is eliminated from the upper respiratory tract by host immune factors in 50
percent of cases at one month following acute infection [16].

Additional issues related to antibiotic therapy for reducing transmission are discussed
further below. (See 'Follow-up' below.)
TREATMENT Antimicrobial therapy is warranted for patients with symptomatic
pharyngitis if the presence of group A streptococci (GAS) in the pharynx is confirmed by
culture or rapid antigen detection testing (RADT) [17]. The approach to establishing the
diagnosis of acute streptococcal pharyngitis is discussed in detail separately.
(See "Evaluation of acute pharyngitis in adults", section on 'Identifying patients with GAS'.)

Antimicrobial therapy may also be administered to mitigate the clinical course of


pharyngitis due to group C and group G streptococci. The approach to antibiotic selection
is as outlined in the following sections. However, treatment need not continue for 10 days
since acute rheumatic fever is not a complication of infection due to these organisms; five
days of treatment is sufficient [2,18,19]. (See "Group C and group G streptococcal
infection".)

In general, antimicrobial therapy is of no proven benefit for treatment of pharyngitis due to


bacteria other than Streptococcus (with the exception of relatively rare infections caused
by other bacterial pathogens such as Corynebacterium diphtheriae and Neisseria
gonorrhoeae). Such therapy unnecessarily exposes patients to the expense and potential
hazards of antimicrobial drugs and contributes to the emergence of antibiotic-resistant
bacteria.

Timing of therapy If clinical and/or epidemiologic factors point to a high index of


suspicion for GAS pharyngitis while laboratory results are pending, it is appropriate to
initiate empiric antimicrobial therapy. However, if laboratory testing does not confirm the
diagnosis of GAS pharyngitis, antimicrobial therapy should be discontinued.

In the natural history of GAS pharyngitis, the incubation period is two to four days. Fever
and constitutional symptoms usually resolve within three to four days, even in the absence
of antimicrobial therapy [16]. Clinical improvement has been observed up to 48 hours
sooner in patients receiving penicillin versus placebo within the first two days of illness [5-
9].

Treatment is warranted for patients with negative rapid antigen detection testing but
subsequent positive culture results whose symptoms are resolving, in order to reduce the
likelihood of transmission.

There is some concern that early therapy may suppress host antibody response and
thereby increase risk for recurrent pharyngitis. In a study of 142 children with presumed
GAS pharyngitis, those treated with penicillin at the initial office visit had a higher incidence
of recurrent infection than those for whom treatment was delayed at least 48 hours
(recurrent infection occurred eight times more frequently) [6].

Nonetheless, delaying treatment is not warranted in most cases of GAS tonsillopharyngitis.


It may be a useful strategy for patients who have frequent, recurrent, mild to moderate
infections to allow development of immunity to the infecting strain without increasing the
risk of acute rheumatic fever. Antibiotic therapy delayed for up to nine days following onset
of symptoms is still helpful for prevention of rheumatic fever (although may be less
effective for prevention of suppurative complications) [12]. However, this approach should
not be considered if the patient is severely ill or if highly virulent or rheumatogenic strains
are actively circulating within a community. Patients are considered no longer contagious
after 24 hours of antibiotic therapy [14].

Antibiotics for group A Streptococcus Antibiotic options for treatment of GAS


pharyngitis include penicillin (and other related agents including ampicillin and amoxicillin),
cephalosporins, macrolides, and clindamycin [20]. Sulfonamides, fluoroquinolones, and
tetracyclines should NOT be used for treatment of GAS pharyngitis because of high rates
of resistance to these agents and their frequent failure to eradicate even susceptible
organisms from the pharynx.

Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of
rheumatic fever in controlled studies [13,21]. These studies were performed with penicillin
G procaine in oil containing aluminum monostearate; this preparation has since been
supplanted by penicillin G benzathine. There are data suggesting that penicillin G
benzathine is effective for primary prevention of rheumatic fever, although they are not
definitive [22]. Other antimicrobials have been shown to effectively eradicate GAS from the
upper respiratory tract, and it is assumed that such eradication is a surrogate for efficacy in
primary prevention of rheumatic fever.

Resistance Antimicrobial resistance has not been a significant issue in the treatment of
GAS. No clinical isolate of GAS has demonstrated penicillin resistance, likely due to the
organism's lack of altered penicillin-binding proteins and/or inefficient gene transfer
mechanisms for resistance [23,24]. However, streptococcal strains tolerant to penicillin
(eg, strains inhibited but not killed by penicillin in vitro, with ratio of minimum bactericidal
concentration to minimum inhibitory concentration [MIC] of 32) have been described [25-
28]. The clinical significance of such strains is not clear; they have been isolated in the
setting of outbreaks in which penicillin treatment failure was observed, but there was no
difference in failure rates among tolerant and susceptible strains. (See "Antibiotic failure in
the treatment of streptococcal tonsillopharyngitis".)

There have been reports of relatively high levels of resistance to macrolide antibiotics in
some regions of the United States and Asia; given the increasing use of macrolides for
treatment of upper and lower respiratory tract infections, clinicians should be cognizant of
local patterns of antimicrobial resistance [29-39].

Selection Oral penicillin V is the agent of choice for treatment of GAS pharyngitis given
its proven efficacy, safety, narrow spectrum, and low cost [2,40-44]. The appropriate
duration is 10 days of therapy; dosing is outlined in the Table (table 3). This approach is
extrapolated from studies performed in the 1950s demonstrating that treatment of
streptococcal pharyngitis with intramuscular penicillin prevents acute rheumatic fever
[13,21]. (See "Acute rheumatic fever: Treatment and prevention".)
Amoxicillin is often used in place of oral penicillin in children, since the taste of the
amoxicillin suspension is more palatable than that of penicillin. Some data suggest that
oral amoxicillin may be marginally superior to penicillin, most likely due to better
gastrointestinal (GI) absorption [45,46]. In addition, amoxicillin has activity against one-
third of the common pathogens that cause otitis media (which presents concurrently with
GAS tonsillopharyngitis in up to 15 percent of children, particularly those under four years
of age). Dosing is outlined in the Table (table 3). (See "Acute otitis media in children:
Treatment", section on 'Initial antimicrobial therapy'.)

Intramuscular penicillin G benzathine (single dose) may be administered to patients who


cannot complete a 10-day course of oral therapy or to patients at enhanced risk for
rheumatic fever (eg, those with history of previous rheumatic heart disease and/or living in
crowded conditions). Injections of penicillin G benzathine provide bactericidal levels
against GAS for 21 to 28 days. The addition of procaine penicillin alleviates some of the
discomfort associated with benzathine injections and may favorably influence the initial
clinical response. The preferred product in children is the combination of 900,000 units of
penicillin G benzathine plus 300,000 units of procaine penicillin (Bicillin C-R 900/300).
Dosing is outlined in the Table (table 3).

Cephalosporins are acceptable alternatives in patients with recurrent GAS infection but are
not recommended as first-line therapy in national guidelines [47-54]. Cephalosporins have
demonstrated better microbiologic and clinical cure rates than penicillin; these differences
appear to be greater among children than adults, and some favor use of first-generation
cephalosporins as first-line therapy in this group [55-57]. However, second- and third-
generation cephalosporins may facilitate development of antibiotic resistance and are not
favored as first-line therapy [48,49]. (See 'Recurrent infection' below.)

Antibiotic therapy directed against beta-lactamaseproducing upper respiratory tract flora


(such as amoxicillin-clavulanate) remains controversial and is not indicated in patients with
acute pharyngitis, although it would be effective [2,58,59].

For patients with penicillin hypersensitivity, cephalosporins


(cefuroxime, cefpodoxime, cefdinir, and ceftriaxone) may be used [40,46-52], in the
absence of history of life-threatening allergic reaction to penicillin; cross reactivity with
penicillin is not likely for later-generation cephalosporins [47,60-62]. Macrolides
(azithromycin, clarithromycin, or erythromycin) are an acceptable alternative for penicillin-
allergic patients, depending on local resistance patterns, as resistance rates can be as
high as 20 percent [2,32,34-37,43,63-66].

There are a number of acceptable dosing regimens for azithromycin (table 3); these
include the following:

Five-day course
12 mg/kg (not to exceed 500 mg) on day 1, followed by 6 mg/kg (not to exceed
250 mg) on days 2 through 5 [36,43,63]
12 mg/kg (not to exceed 500 mg) on days 1 through 5 [2,64,66]
Three-day course: 20 mg/kg (not to exceed 500 mg) on days 1 through 3 [37,65,66]

Data from studies in adults form the basis for the five-day course of 12 mg/kg on day 1
followed by 6 mg/kg on days 2 through 5; data from studies in children form the basis for
the five-day course of 12 mg/kg and the three-day course of 20 mg/kg.

For the rare patient with an erythromycin-resistant strain of GAS who is unable to tolerate
beta-lactam agents, clindamycin is an appropriate choice [29,33,67]. (See "Penicillin-
allergic patients: Use of cephalosporins, carbapenems, and monobactams".)

Duration In general, the conventional duration of oral antibiotic therapy to achieve


maximal pharyngeal GAS eradication rates is 10 days, even though patients usually
improve clinically within the first few days of treatment [68,69]. If penicillin is discontinued
after three days of therapy, the probability of relapse is higher than if penicillin is
discontinued after seven days of treatment (50 versus 34 percent, respectively) [13,16,21].

Five days of therapy with cefpodoxime or cefdinir is an acceptable alternative approach,


with rates of bacteriologic and clinical cure of streptococcal pharyngitis comparable with
that of the conventional 10-day course of penicillin [37,43,70-82]. Three injections
of ceftriaxone on sequential days (or every other day) are needed for optimal eradication.

Azithromycin may be administered as a five-day or three-day regimen [34-37,65,66].


(See 'Selection' above.)

Attempts to treat GAS pharyngitis with a single daily dose of penicillin have been
unsuccessful. Although some data suggest that once-daily amoxicillin may be sufficient for
treatment of GAS pharyngitis, others have shown that this approach is not adequate for
effective eradication; further investigation is needed [83-86]. Among the alternative
agents, azithromycin and some cephalosporins
(including cefixime, cefpodoxime, cefadroxil, and cefdinir) are effective for eradication of
pharyngeal streptococci with once-daily dosing [75,87-90].

Antibiotics for other organisms The differential diagnosis of acute pharyngitis is


outlined separately (table 4). (See "Evaluation of acute pharyngitis in adults".)

The approach to treatment of infection due to Streptococcus other than group A, influenza,
infectious mononucleosis, primary HIV infection, N. gonorrhoeae, Mycoplasma
pneumoniae, Chlamydia pneumoniae, and Corynebacterium diphtheriae is discussed
separately. (See related topics.)

The approach to treatment of infection due to Fusobacterium necrophorum is uncertain;


further study is needed to better define the role of F. necrophorum in the epidemiology of
pharyngitis and the associated risk between F. necrophorum pharyngitis and Lemierre's
syndrome. Some favor empiric treatment in the setting of negative diagnostic test results
but at least three Centor criteria (fever, tonsillar exudate, swollen tender cervical
adenopathy, or lack of cough) among patients 15 to 30 years of age, although it is
uncertain whether this approach is effective for prevention of Lemierre's syndrome [91-93].
In general, we favor treatment for pharyngitis only in the setting of a positive diagnostic
test [43]. Antibiotic therapy for pharyngitis attributed to F. necrophorum should consist of a
penicillin or cephalosporin; azithromycin lacks activity. (See "Suppurative (septic)
thrombophlebitis", section on 'Jugular vein' and "Evaluation of acute pharyngitis in adults",
section on 'Evaluation'.)

The antibiotics of choice for treatment of infection due to Arcanobacterium


haemolyticum are erythromycin or azithromycin; data are limited to case reports and in
vitro studies [94,95]. In vitro studies show most strains to be susceptible to beta-lactam
agents, although treatment failure may occur because of poor penetration into the
intracellular space [95]. Clindamycin, doxycycline, ciprofloxacin, and vancomycin are also
effective agents.

Follow-up Patients with GAS pharyngitis should have improvement in clinical


symptoms within three to four days of initiating antibiotic therapy. Patients are considered
no longer contagious after 24 hours of antibiotic therapy [14]. Patients may return to
daycare, school, camp, or work after 24 hours of antibiotics; one study suggests children
treated with amoxicillin for streptococcal pharyngitis by 5:00 pm may be permitted to
attend school the following day if afebrile and clinically improved [15].

Failure to observe a clinical response to antibiotics should prompt diagnostic


reconsideration or the possibility of a suppurative complication. If acute streptococcal
pharyngitis was diagnosed by rapid testing, the result may represent a false-positive
finding; if the diagnosis was made by culture, the patient may be a pharyngeal carrier
whose symptoms are likely attributable to an alternate process. (See 'Carriers' below.)

In general, test of cure is not necessary for asymptomatic patients or their close contacts
following completion of a course of antimicrobial therapy. The majority of patients with GAS
remaining in their upper respiratory tracts after completing a course of antimicrobial
therapy are asymptomatic Streptococcus carriers [96,97].

However, follow-up test of cure is appropriate testing for asymptomatic index patients and
their asymptomatic household contacts in the following circumstances:

Individuals with history of rheumatic fever


Individuals who develop acute pharyngitis during an outbreak of acute rheumatic
fever or acute poststreptococcal glomerulonephritis [97]
Spread of GAS among several family members
Asymptomatic patients and asymptomatic household contacts in the above circumstances
with positive laboratory results should receive a standard course of antimicrobial therapy
with one of the agents outlined above [98]. Repeat treatment should be administered with
an agent with greater beta-lactamase stability than the previous agent [58]. If a penicillin
was used for initial therapy, repeat treatment with amoxicillin-clavulanate or a first-
generation cephalosporin may be used; if initial treatment was with a first-generation
cephalosporin, a second- or third-generation cephalosporin may be used. First-generation
cephalosporins regimens include cephalexin and cefadroxil; second generation regimens
include cefprozil, cefuroxime, and cefaclor; third-generation cephalosporins
include cefdinir, cefpodoxime, and cefixime. (See "Evaluation of acute pharyngitis in
adults" and 'Antibiotics for group A Streptococcus' above.)

Recurrent infection In the setting of recurrent acute pharyngitis with positive repeat
diagnostic testing, there are several possible explanations [96,98,99]:

Persistence of Streptococcus carriage in the setting of viral infection


Nonadherence with the prescribed antimicrobial regimen
New infection with GAS acquired from household or community contacts
Treatment failure (eg, repeat episode of pharyngitis caused by the original infecting
strain); treatment failure is rare.

In the setting of a second episode of acute pharyngitis with positive repeat diagnostic
testing, a repeat course of treatment is appropriate (table 3). Repeat treatment should be
administered with an agent with greater beta-lactamase stability than the previous agent
[58].

If adherence is uncertain, intramuscular penicillin G benzathine may be chosen as the


second course of therapy. If a full course of penicillin was completed as initial therapy, a
first-generation cephalosporin (such as cephalexin, cefadroxil) may be used; if a first-
generation cephalosporin was used for initial therapy, a second- or third-generation
cephalosporin (such as cefpodoxime, cefdinir) may be used. Alternative agents
include amoxicillin-clavulanate or clindamycin.

It is not necessary to perform follow-up testing after the second course of therapy unless
the patient remains or becomes symptomatic or unless special circumstances as outlined
above are present. (See 'Antibiotics for group A Streptococcus' above and 'Follow-
up' above.)

In the setting of multiple recurrent episodes, it may be difficult to distinguish true GAS
pharyngitis from viral pharyngitis in the setting of streptococcal carriage. It is likely that
most of these patients are carriers experiencing nonstreptococcal infections. This may be
discernible by evaluating for the presence of GAS during asymptomatic intervals and/or by
typing streptococcal isolates obtained during distinct episodes (with the expertise of a
specialized laboratory). In these circumstances, treatment with clindamycin or amoxicillin-
clavulanate may be beneficial since these agents have demonstrated high eradication
rates for pharyngeal streptococci carriage (table 3) [58,67,100]. (See 'Carriers' below.)

For patients with as many as six GAS infections in a single year or three to four episodes
in two consecutive years, tonsillectomy may be an appropriate therapeutic consideration
[101,102]. This was illustrated in a randomized trial including 187 children with recurrent
pharyngitis, of whom 95 were managed with tonsillectomy [101]. The incidence of
pharyngitis during the first two years of follow-up was significantly lower among the
tonsillectomy group. (See "Tonsillectomy and/or adenoidectomy in children: Indications
and contraindications", section on 'Recurrent throat infection'.)

Antibiotic failure in the treatment of streptococcal tonsillopharyngitis is discussed


separately. (See "Antibiotic failure in the treatment of streptococcal tonsillopharyngitis".)

PREVENTION

Carriers In general, group A Streptococcus (GAS) resides in the oropharynx


of Streptococcus carriers in the absence of host immunologic response to the organism
[103]. In temperate climates during the winter and spring, up to 20 percent of
asymptomatic school-aged children may be carriers. About 25 percent of asymptomatic
individuals in the households of index patients harbor GAS in their upper respiratory tracts
[98]. Streptococcal carriage may persist for many months. (See "Antibiotic failure in the
treatment of streptococcal tonsillopharyngitis", section on 'Streptococcal carriage'.)

Carriers may demonstrate evidence of GAS in the upper respiratory tract during an
episode of viral pharyngitis, suggesting acute streptococcal pharyngitis. In these
circumstances, clinically distinguishing viral from streptococcal pharyngitis can be difficult.
Useful clues may include patient age, season, local epidemiology, and the nature of
presenting signs and symptoms. In addition, pharyngeal strep carriers tend to have low
antistreptolysin O (ASO) titers; they may be just above detectable. (See "Evaluation of
acute pharyngitis in adults".)

Streptococcus carriers are unlikely to spread the organism to close contacts and are at
very low risk for developing suppurative complications or acute rheumatic fever [103].
Moreover, eradication of GAS from the upper respiratory tract of carriers is much more
difficult than eradication of GAS from patients with acute infection [52,96,104]. In general,
except for the circumstances described above, Streptococcus carriers do not require
antimicrobial therapy. (See 'Follow-up' above.)

Foodborne illness Streptococcal contamination of food has been implicated in


foodborne outbreaks of pharyngitis [105-109], and foodborne transmission of GAS
pharyngitis by asymptomatic food service workers with nasopharyngeal carriage has been
reported [108,110,111]. Factors that can reduce foodborne transmission of GAS
pharyngitis include thorough cooking, complete reheating, and use of gloves while
handling food [105,112].
Prophylaxis Continuous antimicrobial prophylaxis is only appropriate for prevention of
recurrent rheumatic fever in patients who have experienced a previous episode of
rheumatic fever. (See "Acute rheumatic fever: Treatment and prevention", section on
'Secondary prevention (antibiotic prophylaxis)'.)

Vaccination There is no vaccine against GAS available for clinical use, although
development of this preventive measure is under investigation [113,114]. An important area
of uncertainty is whether vaccine-induced antibodies may cross-react with host tissue to
produce nonsuppurative sequelae in the absence of clinical infection.

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Streptococcal tonsillopharyngitis".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, The Basics and Beyond the Basics. The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)

Basics topics (see "Patient education: Sore throat in adults (The


Basics)" and "Patient education: Strep throat in children (The Basics)" and "Patient
education: Scarlet fever (The Basics)")
Beyond the Basics topics (see "Patient education: Sore throat in children (Beyond
the Basics)" and "Patient education: Sore throat in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Goals of antimicrobial therapy for eradication of group A Streptococcus (GAS) from


the pharynx in the setting of acute streptococcal pharyngitis include:
Reducing duration and severity of clinical signs and symptoms, including
suppurative complications
Reducing incidence of nonsuppurative complications (eg, acute rheumatic
fever)
Reducing transmission to close contacts by reducing infectivity (see 'Goals of
therapy' above)
We recommend initiating treatment with antimicrobial therapy for patients with
symptomatic pharyngitis if the presence of group A streptococci in the pharynx is
confirmed by culture or rapid antigen detection testing (RADT) (Grade 1A).
(See 'Treatment' above.)
We suggest initiating treatment with antimicrobial therapy for patients whose
clinical and/or epidemiologic factors point to a high index of suspicion for GAS
pharyngitis while laboratory results are pending (Grade 2B). (See 'Treatment' above.)
Oral penicillin V is the agent of choice for treatment of GAS pharyngitis in many
clinical settings given its proven efficacy, safety, narrow spectrum, and low
cost. Amoxicillin is often used in place of oral penicillin in children, since the taste of
the amoxicillin suspension is more palatable than that of penicillin (table 3). First-
generation cephalosporins (such as cephalexin and cefadroxil) are acceptable
alternatives to penicillin and amoxicillin, especially in the setting of treatment failure or
beta-lactam hypersensitivity. (See 'Selection' above.)
Although most patients improve clinically within the first few days of treatment, the
conventional duration of oral antibiotic therapy is 10 days to achieve maximal
pharyngeal GAS eradication rates. Intramuscular penicillin G benzathine may be
administered to patients who cannot complete a 10-day course of oral therapy.
(See 'Duration' above.)
We suggest NOT treating with antibiotics for pharyngitis in the absence of positive
diagnostic data (Grade 2C). We suggest erythromycin or azithromycin for treatment
of pharyngitis due to Arcanobacterium haemolyticum (Grade 2C). (See 'Antibiotics for
other organisms' above.)
In general, test of cure is not necessary for asymptomatic patients or their close
contacts following completion of a course of antimicrobial therapy, except in unique
circumstances. (See 'Follow-up' above.)
We suggest a repeat course of treatment for patients with a repeat episode of acute
pharyngitis and positive repeat diagnostic testing (Grade 2C). Patients warranting a
repeat course of treatment may receive an agent with greater beta-lactamase stability
than the previous agent. (See 'Recurrent infection' above.)
Patients who are long-term streptococcal carriers may develop multiple episodes of
pharyngitis due to viral infection. In such cases, repeatedly positive cultures or rapid
antigen tests for GAS may be misleading, and further treatment for streptococcal
pharyngitis may not be warranted. Carriers are unlikely to spread the organism to
close contacts and are at very low risk for developing suppurative complications or
acute rheumatic fever. Moreover, eradication of GAS from the upper respiratory tract
of carriers can be difficult and is not necessary. (See 'Carriers' above.)
Sore throat in children and adolescents: Symptomatic treatment

Author:
Jan E Drutz, MD
Section Editor:
Teresa K Duryea, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 16, 2016.

INTRODUCTION Symptomatic relief of sore throat in children and adolescents will be


reviewed here. The evaluation of sore throat in children, the diagnosis and differential
diagnosis of group A streptococcal tonsillopharyngitis in children, and the symptomatic
treatment of sore throat in adults are discussed separately. (See "Evaluation of sore throat
in children" and "Group A streptococcal tonsillopharyngitis in children and adolescents:
Clinical features and diagnosis" and "Symptomatic treatment of acute pharyngitis in
adults".)

CAUSES OF SORE THROAT In children and adolescents, sore throat is usually


caused by a viral infection or group A Streptococcus (table 1). Less common causes
include other bacterial infections, respiratory allergies, inflammatory disease (eg, Behet
syndrome), irritant inhalants, dryness, and trauma (eg, hot liquids, foreign body injury,
caustic ingestion, inhaled toxic gases). (See "Evaluation of sore throat in children", section
on 'Causes'.)

GENERAL MEASURES

Anticipatory guidance Anticipatory guidance for sore throat in children and


adolescents includes education about:

Expected course of illness Throat pain caused by infections usually lasts a few
days and should improve steadily without worsening.
In a 2013 meta-analysis of six randomized trials and one observational study (344
children), sore throat lasted between two to seven days among children who received
control, placebo, or over-the-counter treatment; sore throat resolved by day 3 in
approximately 60 to 70 percent of cases [1]. The duration of symptoms was similar in
children with and without group A streptococcal (GAS) tonsillopharyngitis.
Indications for reevaluation Indications for reevaluation in children and
adolescents with sore throat include:
Difficulty breathing or drooling (may indicate upper airway obstruction)
(see "Emergency evaluation of acute upper airway obstruction in children",
section on 'Infectious etiologies')
Inability to maintain hydration (see "Clinical assessment and diagnosis of
hypovolemia (dehydration) in children", section on 'Clinical assessment')
Worsening pain or pain that persists for >3 days without improvement
(see 'Worsening or persistent pain' below)
Indications for antibiotics and potential harms of inappropriate use
Antibiotics generally are indicated for laboratory-documented bacterial pharyngitis.
They are not helpful in viral pharyngitis and may be associated with adverse effects
including diarrhea, allergy, increased bacterial resistance, unnecessary expense, etc.
(See "Patient education: What you should know about antibiotics (The Basics)".)
Pain management Management of throat pain is discussed below. (See 'Systemic
analgesia' below.)
Safety and efficacy of over-the-counter medications versus complementary
and alternative therapies Over-the-counter medications for the treatment of sore
throat or other inflammatory conditions (not limited to sore throat) must demonstrate
safety and efficacy in clinical studies before approval by the US Food and Drug
Administration (FDA). In contrast, manufacturers of alternative products can claim
efficacy and safety without providing the rigorous documentation of safety and
efficacy.

Treat underlying cause as indicated

Viral infections Viral causes of sore throat that may require antiviral therapy
include:
Influenza A or B viruses (see "Seasonal influenza in children: Prevention and
treatment with antiviral drugs", section on 'Antiviral therapy')
Herpes simplex virus type 1 (herpetic gingivostomatitis) (see "Herpetic
gingivostomatitis in young children", section on 'Oral acyclovir')
Human immunodeficiency virus (see "Selecting antiretroviral regimens for the
treatment-nave HIV-infected patient")
Other viruses that cause pharyngitis generally do not require antiviral therapy in
immunocompetent children and adolescents. These include adenoviruses,
enteroviruses, rhinoviruses, coronaviruses, and parainfluenza viruses 1, 2, and 3 [2].
(See "Diagnosis, treatment, and prevention of adenovirus infection", section on
'Treatment' and "Hand, foot, and mouth disease and herpangina: An overview",
section on 'Management' and "Parainfluenza viruses in children", section on
'Treatment' and "The common cold in children: Management and prevention", section
on 'Sore throat'.)
Bacterial infections Antimicrobial therapy should be provided for patients with
laboratory-documented bacterial pharyngitis/tonsillitis. Antibiotic therapy helps to
prevent complications and the spread of infection [3].
Antimicrobial treatment of bacterial sore throat is discussed separately:
Group A streptococcal pharyngitis (see "Treatment and prevention of
streptococcal tonsillopharyngitis")
For patients with GAS tonsillopharyngitis, early initiation of antibiotic therapy
appears to modestly reduce the duration of symptoms, but antibiotics are less
effective in reducing pain than other interventions (eg, systemic analgesic
agents) [3-6] (see 'Systemic analgesia' below)
Group C and G streptococcal pharyngitis (see "Group C and group G
streptococcal infection", section on 'Treatment')
Arcanobacterium hemolyticum (see "Group A streptococcal tonsillopharyngitis in
children and adolescents: Clinical features and diagnosis", section on 'Other
bacterial infections')
Neisseria gonorrhoeae (see "Treatment of uncomplicated gonococcal
infections", section on 'Pharyngeal infection')
Treponema pallidum (secondary syphilis) (see "Syphilis: Treatment and
monitoring", section on 'Treatment of early syphilis')
Oral anaerobes (acute necrotizing ulcerative gingivitis, also called Vincent
angina and trench mouth) (see "Gingivitis and periodontitis in children and
adolescents: An overview", section on 'Acute necrotizing ulcerative gingivitis')
Yersinia enterocolitica or Y. pestis (see "Treatment and prevention of Yersinia
enterocolitica and Yersinia pseudotuberculosis infection", section on 'Treatment')
Francisella tularensis (see "Clinical manifestations, diagnosis, and treatment of
tularemia", section on 'Treatment')
Corynebacterium diphtheriae (see "Clinical manifestations, diagnosis, and
treatment of diphtheria", section on 'Treatment')
Fungal infections Although oropharyngeal candidiasis usually occurs in infants, it
may occur in older children and adolescents (eg, after a course of systemic
antibiotics) (see "Candida infections in children: An overview", section on
'Oropharyngeal candidiasis')
Allergic rhinitis (see "Pharmacotherapy of allergic rhinitis")
Postoperative tonsillectomy (see "Tonsillectomy (with or without adenoidectomy)
in children: Postoperative care and complications", section on 'Pain')
Behet syndrome (see "Treatment of Behets syndrome", section on
'Mucocutaneous manifestations')
Caustic ingestion (see "Caustic esophageal injury in children", section on 'Initial
management')

Supportive care General supportive measures that can be suggested for most patients
with infectious pharyngitis include [7-10]:

Getting adequate rest


Consuming an adequate volume of fluids
Avoiding cigarette smoke (including second hand smoke) and other respiratory
irritants
Avoiding acidic foods and beverages (particularly for those with oral or pharyngeal
ulcers)
Eating a soft diet (may be more palatable for those with difficulty swallowing due to
pain or enlarged tonsils)

SYMPTOMATIC TREATMENT

Our approach

Soothing measures We offer one or more of the following topical soothing measures
to patients with throat pain. The interventions may be tried in any sequence or combination
at patient/caregiver discretion. Although most of the interventions have not been studied in
clinical trials, they may provide short term-relief and are unlikely to be harmful [7,9].
Adjunctive systemic therapy also may be warranted. (See 'Systemic analgesia' below.)

Sipping cold or warm beverages (eg, tea with honey or lemon) Honey should be
avoided in children <12 months because of the possible contamination of honey
with Clostridium botulinum spores, potentially leading to infantile botulism.
(See "Botulism", section on 'Infant botulism'.)
Eating cold or frozen desserts (eg, ice cream, popsicles)
Sucking on ice
Sucking on hard candy For children 5 years and adolescents, we suggest
sucking on hard candy rather than medicated throat lozenges (eg, cough drops,
troches, or pastilles) or medicated sprays. Hard candy and lozenges should not be
used in children 4 years of age because they are a choking hazard.
Hard candy is probably as effective as medicated lozenges, less expensive, and less
likely to have adverse effects [8,11-13]. (See 'Medicated lozenges and sprays' below.)
Gargling with warm salt water For children 6 years of age and adolescents, we
suggest gargling with warm salt water rather than other medicated oral rinses. Most
recipes call for to teaspoon of salt per 8 ounces (approximately 240 mL) of warm
water. Children <6 years generally cannot gargle properly.
Medicated oral rinses have not been proven to be superior to placebo and have
potential adverse effects (eg, toxicity from systemic absorption, allergic reaction) [14-
17]. (See 'Medicated oral rinses' below.)

Systemic analgesia We recommend systemic analgesia for children and adolescents


with throat pain, particularly if it decreases oral intake. We generally
suggest acetaminophen or ibuprofen rather than other systemic analgesic agents. We use
the following doses:

Acetaminophen 10 to 15 mg/kg orally every four to six hours as needed (maximum


single dose: 1 g; maximum daily dose: 75 mg/kg per day up to 4 g/day; maximum of 5
doses per day)
Ibuprofen 10 mg/kg orally every six hours as needed (maximum single dose 600
mg; maximum daily dose 40 mg/kg per day up to 2.4 g/day)
Although some studies suggest that ibuprofen is more effective than acetaminophen in
reducing throat pain, the additional benefit is small [18], and patients/caregivers may prefer
one or the other agent for a variety of reasons. Aspirin should be avoided in children
because of the risk of Reye syndrome, as well as its antiplatelet effect.

Systemic acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) such


as ibuprofen have been shown to alleviate sore throat pain in randomized controlled trials
and systematic reviews [4,18-23]. In addition, they may alleviate fever and inflammation. In
a systematic review of studies evaluating control of pain of various causes (eg, sore throat,
musculoskeletal trauma, vaccination, etc), both ibuprofen and acetaminophen were more
effective than placebo [18]. In pooled analysis of six randomized trials in children,
ibuprofen was superior to acetaminophen in reducing pain, but the effect was small
(standardized mean difference 0.28, 95% CI 0.10-0.46). The reported rates of adverse
events with ibuprofen and acetaminophen were similar. However, some experts suggest
avoidance of ibuprofen in children with dehydration or at risk of dehydration given the
potential increased risk of renal toxicity [17,24].

Worsening or persistent pain Children and adolescents with sore throat that worsens
or persists for >3 days without improvement should be instructed to return for reevaluation
[9]. Worsening throat pain or throat pain that persists for >3 days without improvement
may indicate the development of a complication (eg, tonsillopharyngeal cellulitis or
abscess, jugular vein septic thrombophlebitis) or the need to consider a different diagnosis
[10]. (See "Peritonsillar cellulitis and abscess" and "Retropharyngeal infections in
children" and "Suppurative (septic) thrombophlebitis", section on 'Jugular
vein' and "Evaluation of sore throat in children".)

Other therapies

Medicated lozenges and sprays We suggest not using medicated lozenges or throat
sprays for relief of throat pain in children and adolescents. Although there is some
evidence from randomized trials that medicated lozenges and sprays provide symptomatic
relief [7,25-28], it is not clear that they work any better than hard candy and have greater
potential for adverse effects [8,11-13]. A 2010 systematic review found no good quality
evidence on the effectiveness of nonprescription lozenges or throat sprays [17].

Medicated lozenges usually are designed to relieve dryness or pain. They commonly
contain menthol (a cooling agent), antiseptics (hexylresorcinol, chlorhexidine), topical
anesthetics (eg, phenol, benzocaine,
hexylresorcinol, benzydamine), and/or antiinflammatory agents (flurbiprofen). Medicated
throat sprays usually contain topical anesthetics (eg, benzocaine, phenol, benzydamine).

Medicated throat lozenges and sprays have the potential to cause allergic reactions, and
those that contain benzocaine may cause methemoglobinemia. Lozenges that contain
benzocaine should not be used in children younger than four years (they are a choking
hazard); sprays that contain benzocaine should not be used in children younger than two
years [14]. (See "Clinical features, diagnosis, and treatment of methemoglobinemia",
section on 'Acquired methemoglobinemia'.)

Medicated oral rinses We suggest not routinely using topical oral therapies
containing lidocaine or other topical therapies (eg, diphenhydramine, Kaolin pectin,
magnesia-alumina [eg, Maalox]) to coat oral lesions and/or soothe pain in children with
throat pain due to oral ulcers (eg, herpetic gingivostomatitis; hand, foot, and mouth
disease) given the lack of evidence of benefit from clinical trials [15], the potential for harm
(eg, toxicity from systemic absorption, allergic reaction) [14,16], and difficulty of application
in young children [29].

We also suggest not using medicated oral rinses for symptomatic relief of throat pain
caused by infectious pharyngitis. A 2010 systematic review found no good quality evidence
on the effectiveness of nonprescription oral rinses [17].

Glucocorticoids We suggest not using glucocorticoids for the symptomatic relief of


throat pain in children and adolescents. Evidence regarding the safety and efficacy of
glucocorticoids for acute pharyngitis in children is limited; safe and effective alternatives
are available (eg, ibuprofen, acetaminophen) [18]. Studies directly comparing analgesics
and glucocorticoids for the relief of throat pain are lacking. (See 'Systemic
analgesia' above.)

A 2012 systematic review evaluated the benefit of oral or intramuscular glucocorticoids in


addition to antibiotics in children and adults with sore throat; hospitalized patients, patients
with infectious mononucleosis, peritonsillar abscess, and post-tonsillectomy patients were
excluded [30]. Although pooled analysis of four studies (286 patients) demonstrated that
glucocorticoids increased complete resolution of pain at 24 hours (39 versus 12 percent,
risk ratio 3.2, 95% CI 2.0-5.0), too few children were included to draw firm conclusions
about the benefits for children [31]. In two trials limited to children with group A
streptococcal GAS pharyngitis [32,33], adding a single dose of glucocorticoid therapy to
antimicrobial therapy did not reduce the time to complete resolution of throat pain. The
rates of recurrence, relapse, and adverse events were similar between glucocorticoid and
placebo recipients, but reporting of adverse events was poor [30], and the analysis may
have been underpowered to detect increased complications [34]. Adverse effects of long-
term glucocorticoid use are discussed separately. (See "Major side effects of systemic
glucocorticoids".)

A 2015 systematic review of randomized trials comparing glucocorticoids with placebo for
relief of symptoms of infectious mononucleosis found insufficient evidence to recommend
glucocorticoids for symptom relief and lack of research addressing adverse effects and
long-term complications [35]. The use of glucocorticoids for symptomatic relief in infectious
mononucleosis, including relief of upper-airway obstruction is discussed separately.
(See "Infectious mononucleosis in adults and adolescents", section on 'Symptomatic
treatment' and "Infectious mononucleosis in adults and adolescents", section on
'Complications including airway obstruction'.)

Alternative therapies We suggest not using complementary alternative therapies (eg,


herbal therapies, homeopathic therapies, dietary supplements, etc) in the treatment of sore
throat in children and adolescents.

Although some of these agents have been studied in randomized trials [36-41], high
quality studies are lacking [42,43], and most have not been studied in children. In addition,
the US Food and Drug Administration (FDA) does not regulate the safety, purity, or
potency of herbal products or dietary supplements (which may vary from lot to lot or
capsule to capsule). These therapies may contain potentially harmful unlabeled
ingredients (pesticides, herbicides, pharmaceuticals, allergens) [44-48]; this is particularly
problematic if the child is taking these nonprescription preparations in addition to
prescribed medications.

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Streptococcal tonsillopharyngitis".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Sore throat in children (The


Basics)" and "Patient education: Strep throat in children (The Basics)" and "Patient
education: What you should know about antibiotics (The Basics)")
Beyond the Basics topics (see "Patient education: Sore throat in children (Beyond
the Basics)")

SUMMARY AND RECOMMENDATIONS

Throat pain may be caused by infections, respiratory allergies, inflammatory


disease, irritant inhalants, dryness, and trauma (table 2). (See 'Causes of sore
throat' above.)
General measures for the management of sore throat include:
Provision of education about the expected course of illness, indications for
reevaluation, indications for antibiotics and potential harms of inappropriate use
of antibiotics, and strategies for pain management (see 'Anticipatory
guidance' above)
Treatment of the underlying cause as indicated (eg, antiviral therapy for
influenza, herpes simplex virus, human immunodeficiency virus; antibiotics for
laboratory documented bacterial pharyngitis/tonsillitis) (see 'Treat underlying
cause as indicated' above)
Supportive care (rest, adequate fluid intake, avoidance of respiratory irritants,
soft diet) (see 'Supportive care' above)
We offer one or more of the following topical therapies to children and adolescents
with throat pain (see 'Soothing measures' above):
Sipping cold or warm beverages
Eating cold or frozen desserts or sucking on ice
Sucking on hard candy rather than medicated lozenges or throat sprays (for
children 5 years of age)
Gargling with warm salt water rather than medicated oral rinses (for children 6
years of age)
We recommend systemic analgesia for children and adolescents with throat pain
(Grade 1A). We use acetaminophen or ibuprofen depending on patient preference.
We use the following doses:
Acetaminophen 10 to 15 mg/kg orally every four to six hours as needed
(maximum single dose: 1 g; maximum daily dose: 75 mg/kg per day up to
4 g/day; maximum of 5 doses per day)
Ibuprofen 10 mg/kg orally every six hours as needed (maximum single dose
600 mg; maximum daily dose 40 mg/kg per day up to 2.4 g/day)

(See 'Systemic analgesia' above.)

Children and adolescents with sore throat that worsens or persists for >3 days
without improvement should be instructed to return for reevaluation. Worsening or
persistent pain may indicate the development of a complication or the need to
consider a different diagnosis. (See 'Worsening or persistent pain' above
and "Evaluation of sore throat in children".)
We suggest not using systemic glucocorticoids for the symptomatic relief of throat
pain in children and adolescents (Grade 2B). The use of glucocorticoids for upper
airway obstruction in infectious mononucleosis is discussed separately.
(See 'Glucocorticoids' above and "Clinical manifestations and treatment of Epstein-
Barr virus infection", section on 'Treatment and prevention'.)
We suggest not using herbal therapies, homeopathic therapies, dietary
supplements, or other complementary/alternative therapies in the treatment of sore
throat in children and adolescents (Grade 2C). (See 'Alternative therapies' above.)
roup A streptococcal tonsillopharyngitis in children and adolescents: Clinical
features and diagnosis

Author:
Ellen R Wald, MD
Section Editors:
Morven S Edwards, MD
Anna H Messner, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Sep 29, 2016.

INTRODUCTION Group A Streptococcus (GAS), also known as Streptococcus


pyogenes, is the most common cause of bacterial pharyngitis in children and adolescents.
The clinical features and diagnosis of GAS pharyngitis in children and adolescents will be
discussed here. The treatment, prevention, and complications of GAS pharyngitis and the
evaluation of acute pharyngitis in children and adults are discussed separately.

(See "Treatment and prevention of streptococcal tonsillopharyngitis" and "Antibiotic


failure in the treatment of streptococcal tonsillopharyngitis".)
(See "Complications of streptococcal tonsillopharyngitis".)
(See "Evaluation of sore throat in children".)
(See "Evaluation of acute pharyngitis in adults".)

MICROBIOLOGY GAS is a facultative, gram-positive coccus that grows in chains. The


only known reservoirs are the skin and mucous membranes of the human host. The
pathogenic mechanisms underlying these infections are poorly understood; they are
discussed separately. (See "Group A streptococcus: Virulence factors and pathogenic
mechanisms".)

EPIDEMIOLOGY GAS is the most common cause of bacterial pharyngitis in children


and adolescents. It accounts for 15 to 30 percent of all cases of pharyngitis in children
between the ages of 5 and 15 years [1-4].

In temperate climates, the incidence of GAS pharyngitis peaks during the winter and early
spring [5]. During these seasons, as many as 35 to 40 percent of cases of pharyngitis in
children and adolescents are caused by GAS.

GAS pharyngitis is most common in school-age children but may occur in younger
children, especially if they have contact with school-age children [5,6]. In a meta-analysis,
the pooled prevalence of GAS among children (<18 years) who presented to an outpatient
clinic or emergency department with sore throat was 37 percent (95% CI 32-43 percent)
[7]. The prevalence among children <5 years was 24 percent (95% CI 21-26 percent).

CLINICAL FEATURES

Children 3 years In children 3 years, GAS pharyngitis typically has an abrupt onset.
Fever, headache, abdominal pain, nausea, and vomiting may accompany the sore throat,
which can lead to poor oral intake [3,8,9]. Additional features may include exudative
tonsillopharyngitis, with enlarged erythematous tonsils, enlarged tender anterior cervical
lymph nodes, palatal petechiae, inflamed uvula, and scarlatiniform rash (erythematous,
finely papular rash which characteristically starts in the groin and axilla and then spreads
to the trunk and extremities, followed by desquamation) (picture 1A-B) [3,8,10]. Symptoms
usually resolve spontaneously in three to five days. (See "Complications of streptococcal
tonsillopharyngitis", section on 'Scarlet fever'.)

No single sign or symptom reliably identifies GAS pharyngitis [3,8,10]. In a meta-analysis,


the following individual findings increased the probability of GAS pharyngitis to >50 percent
in children with sore throat but could not be used for definitive diagnosis [10]:

Scarlatiniform rash (picture 1A-B)


Palatal petechiae
Tonsillar enlargement with or without exudate
Vomiting
Tender cervical nodes

Constellations of symptoms and epidemiologic features have been used to develop clinical
scores in an attempt to predict the likelihood that a throat culture will be positive for GAS
[11-14]. None is sufficiently sensitive and specific to eliminate the need for microbiologic
testing in children and adolescents [3,10,15,16]. However, they may be helpful in
determining a testing strategy. (See 'Choice of test' below.)

Children <3 years Symptoms of streptococcal infections usually are atypical in children
<3 years of age [17]. Instead of a well-defined episode of pharyngitis, they may have
protracted symptoms of nasal congestion and discharge, low-grade fever (eg, <38.3C
[101F]), and tender anterior cervical adenopathy [18]. This GAS symptom complex is
called "streptococcosis."

Infants <1 year of age may present with fussiness, decreased appetite, and low-grade
fever. They often have older siblings or day care contacts with GAS infection.

Complications Although most cases of GAS pharyngitis resolve without complications,


serious nonsuppurative and suppurative complications may occur. Nonsuppurative
complications of GAS pharyngitis include acute rheumatic fever, poststreptococcal
glomerulonephritis, and pediatric autoimmune neuropsychiatric disorders associated with
streptococcus (PANDAS). (See "Complications of streptococcal tonsillopharyngitis",
section on 'Nonsuppurative complications'.)

Suppurative complications of GAS pharyngitis include necrotizing fasciitis, bacteremia,


peritonsillar cellulitis or abscess, otitis media, and sinusitis. (See "Complications of
streptococcal tonsillopharyngitis", section on 'Suppurative complications'.)

DIAGNOSIS

Diagnostic criteria The diagnosis of GAS pharyngitis is supported by a positive


microbiologic test (throat culture or rapid antigen detection test [RADT] for GAS) in a
patient with symptoms of GAS pharyngitis and absence of signs and symptoms of viral
infections (eg, coryza, conjunctivitis, cough, hoarseness, anterior stomatitis, discrete
ulcerative lesions or vesicles, diarrhea). (See 'Clinical features' above and 'Microbiologic
tests' below.)

However, between 5 and 21 percent of children between 3 and 15 years of age are
pharyngeal carriers of GAS [7,19,20]. Neither throat culture nor RADT for GAS can
differentiate patients with acute GAS pharyngitis from GAS carriage with intercurrent viral
illness [3]. Such patients may fail to respond to appropriate therapy for GAS infection.
(See "Treatment and prevention of streptococcal tonsillopharyngitis", section on
'Carriers' and "Antibiotic failure in the treatment of streptococcal tonsillopharyngitis",
section on 'Streptococcal carriage'.)

Identification of GAS carriage is discussed separately. (See "Treatment and prevention of


streptococcal tonsillopharyngitis", section on 'Recurrent infection'.)

Approach to testing Our approach to testing for GAS pharyngitis is generally


consistent with that of the Infectious Diseases Society of America, the American Heart
Association, and American Academy of Pediatrics [3,8,21].

Importance of accurate diagnosis GAS is the most common pharyngitis pathogen


that requires antimicrobial therapy. Depending upon the season, as many as 35 to 40
percent of cases of pharyngitis in children and adolescents are caused by GAS. Timely
treatment of GAS in children and adolescents is necessary to:

Prevent suppurative complications and acute rheumatic fever (see "Complications of


streptococcal tonsillopharyngitis")
Prevent disease transmission, particularly if the patient is a contact of someone with
a history of acute rheumatic fever (ARF) [8] (see "Acute rheumatic fever: Treatment
and prevention", section on 'Secondary prevention (antibiotic prophylaxis)')
Reduce duration and severity of symptoms

Treatment of GAS pharyngitis is discussed separately. (See "Treatment and prevention of


streptococcal tonsillopharyngitis".)
Microbiologic confirmation of GAS in the pharynx before initiation of antibiotic therapy
helps to prevent unnecessary provision of antibiotics to children with viral pharyngitis (most
children with pharyngitis) [22]. (See 'Differential diagnosis' below.)

Whom to test We suggest microbiologic testing for GAS in children and adolescents
with [3,8,21]:

Evidence of acute tonsillopharyngitis (erythema, edema, and/or exudates) or


scarlatiniform rash (picture 1A-B) on physical examination and absence of signs and
symptoms of viral infections (eg, coryza, conjunctivitis, cough, hoarseness, anterior
stomatitis, discrete ulcerative lesions or vesicles, diarrhea). (See 'Viral
infections' below.)
Exposure to an individual with GAS at home or school or a high prevalence of GAS
infections in the community and symptoms of GAS, including (see 'Clinical
features' above):
For children 3 years Pharyngitis, fever, headache, abdominal pain, enlarged
tender anterior cervical lymph nodes, palatal petechiae [3,8,9].
For children <3 years Prolonged nasal discharge, tender anterior cervical
adenopathy, and low-grade fever (eg, <38.3C [101F]), particularly if they have
exposure to contacts with GAS infection [6,17,18].
Clinical scoring systems for GAS are not sensitive or specific enough to eliminate the
need for microbiologic testing in children and adolescents with suspected GAS
[3,10,15,23].
Suspected acute rheumatic fever or poststreptococcal glomerulonephritis.
(See "Acute rheumatic fever: Clinical manifestations and
diagnosis" and "Poststreptococcal glomerulonephritis".)

Whom not to test We recommend not performing microbiologic testing for GAS in
children and adolescents with manifestations suggestive of viral illness (eg, coryza,
conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions or
vesicles, diarrhea) [3,21]. (See 'Viral infections' below.)

Choice of test The diagnosis of GAS pharyngitis is supported by a positive throat


culture or RADT for GAS. (See 'Microbiologic tests' below.)

For children and adolescents in whom microbiologic testing for GAS is necessary:

If throat culture results will be available in 48 hours, we suggest standard throat


culture rather than RADT. We verify a telephone number and obtain a pharmacy
phone number/contact information at the initial encounter.
Although we prefer throat culture, RADT is an alternative to throat culture for children
with a streptococcal score of 5 (ie, those in whom a positive result is most likely)
[12,24]; the streptococcal score gives one point for each of the following [12]:
Age (5 to 15 years)
Season (late fall, winter, early spring)
Evidence of acute pharyngitis (erythema, edema, and/or exudates) on physical
examination
Tender, enlarged (>1 cm) anterior cervical lymph nodes
Middle-grade fever (between 38.3 and 39.4C [101 and 103F])
Absence of usual signs and symptoms associated with viral upper respiratory
tract infections
If throat culture results will take >48 hours or the patient/family does not have
reliable telephone follow-up, we suggest RADT rather than throat culture.

If initial testing with RADT is negative in a child or adolescent, we recommend follow-up


testing with standard throat culture because RADT may miss as many as 30 percent of
cases of GAS pharyngitis [3,21,25-27]. Confirmation of negative RADT with throat culture
is not necessary in adults. The risk of an initial episode of acute rheumatic fever in an adult
with GAS pharyngitis is extremely low, even if the pharyngitis is untreated [3]. (See 'RADT
for GAS' below and "Evaluation of acute pharyngitis in adults", section on 'Rapid antigen
detection test'.)

The strategy of initial testing with throat culture is more cost effective than initial testing
with RADT. Most children who require microbiologic testing for pharyngitis do not have
GAS pharyngitis and will have a negative RADT. Given that negative RADT in children and
adolescents must be confirmed with throat culture, if RADT is used as the initial test, the
majority of children and adolescents who are tested will require both RADT and throat
culture. Limiting RADT to children in whom it is likely to be positive and performing throat
cultures in the remainder minimizes the number of children who require both tests [24].

Specimen collection and processing The key to optimizing detection of GAS in


clinical specimens is appropriate collection and transport of the sample [28]:

Specimens should be obtained before initiation of antimicrobial therapy, since a


single dose of antibiotics can result in a negative culture or RADT.
If RADT is to be performed, we suggest that the throat be swabbed with two swabs
simultaneously [27]. One is used for RADT; if RADT is positive, the second swab can
be discarded. If RADT is negative, the second swab can be used for standard culture.
(See 'Diagnosis' above.)
Specimens should be obtained by vigorous swabbing of both tonsils (or tonsillar
fossae in patients who have undergone tonsillectomy) and the posterior pharynx. The
swab(s) should be moved into and out of the mouth without touching the tongue or
the buccal mucosa. The importance of obtaining an adequate specimen cannot be
overstated; the sensitivity of both culture and RADT correlate with inoculum size
[1,29,30].

Microbiologic tests
Throat culture Throat culture is the reference standard for the diagnosis of acute
pharyngitis due to GAS [8,31]. When performed properly, the sensitivity of throat culture is
90 to 95 percent for GAS [3,21,32]. (See 'Specimen collection and processing' above.)

Throat culture is usually performed on 5 percent sheep blood agar [31]. After incubation for
18 to 24 hours at 35 to 37C, the plate is inspected for a small gray colony that gives rise
to an area of beta hemolysis. If no beta hemolytic colonies are seen after 18 to 24 hours,
the plate should be reincubated for an additional 24 hours before being interpreted as
negative [3,33]. Twenty-five to 40 percent of throat cultures that are ultimately positive for
GAS become positive after 24 hours [34].

Throat culture also can identify other bacteria that cause pharyngitis less commonly than
GAS (eg, group C and group G streptococci, Arcanobacterium haemolyticum). However,
most laboratories do not routinely identify these pathogens in throat cultures unless
specifically requested to do so.

RADT for GAS RADT for GAS, sometimes referred to as rapid streptococcal antigen
tests (RSAT), are based upon enzyme or acid extraction of antigen from throat swabs [35-
38]. RADT results are available at the point of care in the office or emergency department
and, if positive, permit early institution of therapy for GAS pharyngitis. Early institution of
therapy enables earlier resolution of symptoms and return to school. However, early
therapy also predisposes to more frequent recurrences of GAS within 30 days [39,40].

RADT have a specificity of 95 percent and a sensitivity that varies between 70 and 90
percent for GAS [3,32,35-38,41-46]. In a 2016 meta-analysis of studies in which 58,244
children underwent both RADT and throat culture, the pooled sensitivity and specificity of
RADT were 85.6 percent (95% CI 83.3-87.6) and 95.4 percent (95% CI 94.5-96.2),
respectively [46]. Given the high specificity and limited sensitivity of the available tests, a
positive RADT is useful in establishing the diagnosis of GAS pharyngitis, but a negative
RADT does not rule out GAS; back-up throat culture should be performed in children and
adolescents with a negative RADT [3,21,25,26].

Molecular assays We do not routinely use molecular assays (ie, nucleic acid
amplification tests [NAAT], polymerase chain reaction assays [PCR]) for the evaluation of
GAS pharyngitis. Additional evaluation is necessary to confirm the sensitivity and
specificity results in initial studies.

NAAT are used extensively for the diagnosis of infectious diseases [47]. Although they are
highly sensitive for GAS [48], the complexity of these tests frequently requires
performance in a laboratory setting, which increases the turn-around time for results.
However, two PCR assays for GAS pharyngitis that can be performed at the point of care
and provide results in 15 minutes are now available (Cobas Strep A test of the Liat
system, Alere i strep A test) [49,50]. Initial evaluation suggests that these PCR assays
have sensitivity and specificity >98 percent [50], thereby potentially eliminating the need
for follow-up throat culture in children with negative PCR results. Additional evaluation is
necessary before these tests are routinely recommended.

GAS serology Serologic testing for GAS may be necessary to confirm previous
infection in patients who are being evaluated for acute rheumatic fever or
poststreptococcal glomerulonephritis, but it is not helpful in managing patients at the time
of clinical presentation with pharyngitis.

DIFFERENTIAL DIAGNOSIS The differential diagnosis of GAS pharyngitis includes


both infectious and noninfectious causes of pharyngitis. Most children and adolescents
with negative microbiologic tests for GAS have viral pharyngitis, which is a self-limited
condition and can be treated symptomatically. (See "Sore throat in children and
adolescents: Symptomatic treatment", section on 'General measures'.)

Noninfectious causes of pharyngitis usually can be differentiated from GAS with


information from the history. (See "Evaluation of sore throat in children", section on 'Other
conditions'.)

Other infectious causes of pharyngitis Acute infectious pharyngitis in children and


adolescents is caused by a variety of agents (table 1). The frequency of these pathogens
varies according to the age of the child, season, and geographic area.

Microbiologic testing may be necessary to differentiate GAS pharyngitis from other


infectious causes of GAS that require treatment or infection control (table 1) and in
children and adolescents whose symptoms worsen or persist for more than five to seven
days (whether or not they were treated for GAS) [51]. (See "Treatment and prevention of
streptococcal tonsillopharyngitis", section on 'Follow-up'.)

Other bacterial infections Other bacterial causes of pharyngitis that may require
treatment include:

Group C and G streptococci Group C and G streptococci have been reported to


cause epidemic and sporadic pharyngitis in school-age children and adults, although
there has been some controversy over their etiologic role [52-55]. Group C or G
streptococci may be identified with standard throat culture, but most laboratories do
not routinely identify them unless specifically requested to do so. Group C or group G
streptococcal pharyngitis may warrant treatment if the patient remains symptomatic
when the results of the culture are available. (See "Group C and group G
streptococcal infection", section on 'Treatment'.)
Neisseria gonorrhoeae N. gonorrhoeae is a relatively rare cause of pharyngitis
but may occur in patients with oral-genital contact. Most cases are asymptomatic;
when present, findings are nonspecific (eg, pharyngeal erythema, edema, or
exudate). Evaluation for gonococcal pharyngitis with a nucleic acid amplification test
(NAAT) or throat culture on media specific for N. gonorrhoeae may be warranted in
patients with risk factors (eg, unprotected oral genital contact). If N. gonorrhoeae is
detected, treatment is necessary to prevent transmission and disseminated disease.
(See "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in
adults and adolescents", section on 'Patients with extragenital
symptoms' and "Treatment of uncomplicated gonococcal infections", section on
'Pharyngeal infection'.)
Fusobacterium necrophorum F. necrophorum causes most cases of jugular vein
suppurative thrombophlebitis (Lemierre syndrome). Lemierre syndrome
predominantly affects previously healthy adolescents and young adults. Clinical
features include high fever (>39C [102.2F]), rigors, respiratory symptoms, and
unilateral neck swelling or pain, findings typically absent in GAS pharyngitis. The
diagnosis and treatment of Lemierre syndrome are discussed separately.
(See "Suppurative (septic) thrombophlebitis", section on 'Jugular vein'.)
The potential roles of F. necrophorum in acute pharyngitis and of F.
necrophorum pharyngitis in the development of Lemierre syndrome are discussed
separately. (See "Evaluation of acute pharyngitis in adults", section on 'Other
bacteria'.)
A. haemolyticum A. haemolyticum pharyngitis occurs predominantly in
adolescents [56-58]. Clinical features overlap with those of GAS and include fever,
exudative pharyngitis, and rash on the extensor surfaces of the arms (picture 2)
[57,59]. The rash occurs in approximately one-half of patients, but in contrast with the
rash of scarlet fever, does not peel [56,57,59]. A. haemolyticum grows slowly on
sheep blood agar plates and produces a tiny zone of beta hemolysis after 48 to 72
hours. Detection is improved (larger colony size and wider zone of hemolysis) by
culture on human or rabbit blood agar [60]. In in vitro studies, A. haemolyticum was
unresponsive to penicillin; erythromycin is the drug of choice [56].
Diphtheria Diphtheria is uncommon in developed countries but is important to
consider in patients from endemic areas. In contrast with GAS pharyngitis, which has
acute onset, the onset of symptoms in diphtheria is usually gradual, beginning with
mild pharyngeal injection and erythema. The hallmark of diphtheria is the formation of
a tightly adhering gray membrane in the nares and throat (picture 3). This membrane
occurs in at least one-third of patients and causes bleeding when it is dislodged.
(See "Clinical manifestations, diagnosis, and treatment of diphtheria", section on
'Respiratory diphtheria' and "Epidemiology and pathophysiology of diphtheria",
section on 'Epidemiology'.)
Tularemia Tularemia is an uncommon cause of pharyngitis that should be
considered in patients with pharyngitis unresponsive to penicillin. It is usually acquired
by ingestion of poorly cooked wild animal meat or contaminated water. Clinical
features of oropharyngeal tularemia include fever, painful ulcerative-exudative
pharyngitis, and cervical lymphadenitis. (See "Epidemiology, microbiology, and
pathogenesis of tularemia", section on 'Epidemiology' and "Clinical manifestations,
diagnosis, and treatment of tularemia".)
Mycoplasma pneumoniae M. pneumoniae can cause pharyngitis and other
respiratory tract illness in children 6 years. M. pneumoniae accounts for 5 to 16
percent of cases of pharyngitis; the wide range may be related to the cyclicity of M.
pneumoniae epidemics [61,62]. (See "Mycoplasma pneumoniae infection in children",
section on 'Respiratory tract disease'.)

Viral infections Viruses are the most common cause of acute pharyngitis (table 1)
[31,63,64]. Clinical features suggestive of viral etiology include concurrent conjunctivitis,
coryza, cough, hoarseness, anterior stomatitis, discrete ulcerative lesions, viral
exanthems, and/or diarrhea [3].

Viral infections in the differential diagnosis of GAS pharyngitis in children and adolescents
that have important management or infection control implications include:

Infectious mononucleosis Epstein-Barr virus (EBV) and cytomegalovirus (CMV)


account for most cases of infectious mononucleosis, a clinical syndrome that
classically occurs in adolescents and is characterized by fever, severe pharyngitis
(which lasts longer than pharyngitis due to GAS), and anterior and posterior cervical
or diffuse lymphadenopathy, lymphocytosis, and increased aminotransferase levels
[65,66]. Prominent constitutional symptoms include fatigue, anorexia, and weight loss.
Examination findings may include periorbital or palpebral edema, mild hepatomegaly,
and splenomegaly. Patients who are treated with ampicillin, amoxicillin, or other
antibiotics may develop a characteristic rash (picture 4). Laboratory findings may
include increased aminotransferases and predominance of atypical lymphocytes in
the differential blood count. (See "Infectious mononucleosis in adults and
adolescents".)
Unlike adolescents, who typically present with classic symptoms, younger patients
with EBV infection may have a more subtle presentation that can make diagnosis
difficult. (See "Clinical manifestations and treatment of Epstein-Barr virus infection",
section on 'Primary infection'.)
Patients with infectious mononucleosis and splenomegaly require activity restriction to
prevent splenic rupture. (See "Infectious mononucleosis in adults and adolescents",
section on 'Return to sports'.)
Primary human immunodeficiency virus (HIV) infection Primary HIV infection
may cause an acute retroviral syndrome (similar to infectious mononucleosis) in
sexually active adolescents or rarely in children who have been sexually abused. The
onset of symptoms usually occurs within days to weeks after the initial exposure.
Clinical features of primary HIV infection include prominent cervical or generalized
adenopathy and persistent constitutional complaints (eg, fever, weight loss).
Laboratory features may include lymphopenia and increased aminotransferase levels.
(See "Acute and early HIV infection: Pathogenesis and epidemiology" and "Acute and
early HIV infection: Clinical manifestations and diagnosis".)
Herpes simplex virus (HSV) HSV pharyngitis should be considered in children
and adolescents with the characteristic enanthem or ulcerative lip lesion. HSV
pharyngitis in children and adolescents may respond to acyclovir therapy.
(See "Herpetic gingivostomatitis in young children" and "Clinical manifestations and
diagnosis of herpes simplex virus type 1 infection", section on
'Diagnosis' and "Treatment of herpes simplex virus type 1 infection in
immunocompetent patients".)
Influenza Influenza infection is characterized by fever, cough, headache, and
myalgias that occur in seasonal epidemics. Pharyngitis caused by influenza may be
exudative. Influenza pharyngitis should be considered in children and adolescents
with fever and severe illness (pharyngitis, cough, or both in the absence of another
known cause of illness) during influenza season (regardless of influenza
immunization status [67]. Antiviral therapy is indicated for children at risk for
complications or severe disease (table 2). Laboratory confirmation should not delay
initiation of treatment. (See "Seasonal influenza in children: Clinical features and
diagnosis", section on 'Diagnosis' and "Seasonal influenza in children: Prevention and
treatment with antiviral drugs", section on 'Antiviral therapy'.)
Enteroviruses Enteroviruses, specifically coxsackie A viruses, cause herpangina,
which is characterized by small vesicles in the posterior pharynx. In one series of 50
children (aged 1 to 10 years) with acute pharyngitis, enterovirus polymerase chain
reaction was positive in 8 percent [68]. (See "Clinical manifestations and diagnosis of
enterovirus and parechovirus infections".)
Adenovirus Adenovirus may manifest as pharyngitis, tonsillitis, or
pharyngoconjunctival fever. There are no distinguishing characteristics of infections
caused by adenovirus except in patients with pharyngoconjunctival fever. The
presence of exudate is variable. (See "Epidemiology and clinical manifestations of
adenovirus infection".)

When pharyngitis is part of a viral syndrome that causes nasopharyngitis, nasal


congestion and discharge may be more prominent than sore throat. These infections
generally resolve with symptomatic therapy. (See "The common cold in children:
Management and prevention", section on 'Symptomatic therapy'.)

Viruses that cause nasopharyngitis include:

Rhinoviruses (see "Epidemiology, clinical manifestations, and pathogenesis of


rhinovirus infections", section on 'Clinical illness')
Coronaviruses (see "Coronaviruses", section on 'Clinical manifestations')
Respiratory syncytial virus (see "Respiratory syncytial virus infection: Clinical
features and diagnosis", section on 'Clinical manifestations')
Parainfluenza viruses (see "Parainfluenza viruses in children", section on 'Clinical
presentation')
Noninfectious causes of pharyngitis Noninfectious causes of sore throat include
irritation or drying of the pharynx, foreign body (eg, fish bone), chemical exposure, referred
pain from extrapharyngeal sources (eg, dental abscess, otitis media). These can usually
be differentiated from infectious pharyngitis through information from the history or
physical examination. (See "Evaluation of sore throat in children", section on 'Other
conditions'.)

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Streptococcal tonsillopharyngitis".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

Basics topics (see "Patient education: Strep throat in children (The


Basics)" and "Patient education: Sore throat in children (The Basics)")
Beyond the Basics topic (see "Patient education: Sore throat in children (Beyond the
Basics)")

SUMMARY AND RECOMMENDATIONS

Group A Streptococcus (GAS) is the most common cause of bacterial pharyngitis in


children and adolescents. It accounts for 15 to 30 percent of all cases of pharyngitis in
children between the ages of 5 and 15 years. In temperate climates, the incidence of
GAS pharyngitis peaks during the winter and early spring.
(See 'Epidemiology' above.)
GAS pharyngitis typically has an abrupt onset. Fever, headache, abdominal pain,
nausea, and vomiting may accompany the sore throat. Additional features may
include exudative pharyngitis, enlarged tender anterior cervical lymph nodes, palatal
petechiae, inflamed uvula, and scarlatiniform rash (picture 1A-B). Symptoms usually
resolve spontaneously in three to five days. (See 'Clinical features' above.)
The diagnosis of GAS pharyngitis is supported by a positive microbiologic test
(throat culture or rapid antigen detection test [RADT] for GAS) in a patient with
symptoms of GAS pharyngitis and absence of signs and symptoms of viral infections
(eg, coryza, conjunctivitis, cough, hoarseness, anterior stomatitis, discrete ulcerative
lesions or vesicles, diarrhea). In children and adolescents, GAS pharyngitis should be
confirmed microbiologically before antimicrobial therapy is initiated. (See 'Diagnostic
criteria' above and "Treatment and prevention of streptococcal tonsillopharyngitis".)
We suggest microbiologic testing for GAS in children and adolescents with
(see 'Whom to test' above):
Evidence of acute pharyngitis (erythema, edema, and/or exudates) or
scarlatiniform rash (picture 1A-B) on physical examination and absence of signs
and symptoms of viral infections
Exposure to an individual with GAS at home or school or a high prevalence of
GAS infections in the community and symptoms of GAS
Suspected acute rheumatic fever or poststreptococcal glomerulonephritis
For children and adolescents in whom microbiologic testing for GAS is necessary,
we suggest initial testing with a standard throat culture; if throat culture results will not
be available for more than 48 hours, we suggest RADT. (See 'Choice of test' above.)
The differential diagnosis of GAS pharyngitis includes both infectious and
noninfectious causes. Most children and adolescents with negative microbiologic
tests for GAS have viral pharyngitis, which is a self-limited condition and can be
treated symptomatically without additional testing. Additional testing may be
necessary to differentiate GAS pharyngitis from other infectious causes of GAS that
require treatment or infection control (table 1) and in children and adolescents whose
symptoms worsen or persist for more than five to seven days (whether or not they
were treated for GAS). (See 'Differential diagnosis' above.)
Educacin para el paciente: Dolor de garganta en nios (Conceptos Bsicos)

View in English
Redactado por los mdicos y editores de UpToDate

Cundo debo llamar al mdico si mi hijo tiene dolor de garganta? El dolor de


garganta es un problema comn en los nios que por lo general mejora por s solo. Sin
embargo, a veces el dolor de garganta puede ser grave.

Llame al mdico o enfermero de su hijo si este tiene dolor de garganta y:

Tiene al menos 101 F o 38.4 C de fiebre


No quiere comer ni beber nada

Pida una ambulancia (en EE. UU. y Canad, marque 9-1-1) o lleve a su hijo a la sala de
emergencia si el nio:

Tiene dificultad para respirar o tragar


Babea mucho ms de lo habitual
Tiene el cuello rgido o inflamado
Cul es la causa del dolor de garganta? En general, el dolor de garganta aparece a
causa de una infeccin. Dos tipos de grmenes pueden provocarla: virus y bacterias. Los
nios esparcen grmenes fcilmente porque con frecuencia se tocan entre s, comparten
juguetes y se colocan objetos en la boca.

Los nios que tienen un dolor de garganta causado por un virus por lo general no tienen
que consultar a un mdico o enfermero, pero si el dolor aparece debido a una bacteria
entonces podran tener que hacerlo, ya que es posible que tengan un tipo de infeccin
llamada infeccin por estreptococo. (Ver "Educacin para el paciente: Infeccin en la
garganta por estreptococo en nios (Conceptos Bsicos)").

Cmo puedo saber si el dolor de garganta de mi hijo fue causado por un virus o
por un estreptococo? Es difcil detectar la diferencia, pero se pueden buscar algunos
indicios (figura 1).

En general, las personas que tienen un dolor de garganta causado por un virus tambin
tienen otros sntomas, como por ejemplo:

Escurrimiento nasal
Pecho congestionado
Comezn en los ojos u ojos rojos
Tos
Voz spera (ronca)
Dolor en el paladar

Las personas que tienen infeccin por estreptococo no suelen tener tos, escurrimiento
nasal, comezn en los ojos ni ojos enrojecidos.

Si cree que su hijo puede tener una infeccin por estreptococo, llame al mdico. l puede
hacer una prueba para detectar la bacteria que causa la infeccin por estreptococo.

Mi hijo debe tomar antibiticos? Si la causa del dolor de garganta es un virus, su


hijo no necesita antibiticos. Salvo que su hijo tenga una infeccin por estreptococo, los
antibiticos no ayudan.

Qu puedo hacer para ayudar a mi hijo a sentirse mejor? Hay varias maneras de
aliviar el dolor de garganta:

Alimentos y bebidas calmantes Dele a su hijo alimentos que sean fciles de


tragar, como t o sopa, o paletas para chupar. Es posible que su hijo no tenga ganas
de comer ni beber, pero es importante que reciba suficiente lquido. Ofrzcale
diferentes bebidas tibias y fras para que pruebe.
Medicinas El paracetamol (acetaminofn; ejemplo de nombre comercial: Tylenol)
o el ibuprofeno (ejemplos de nombres comerciales: Advil, Motrin) pueden ayudar a
aliviar el dolor de garganta. La dosis correcta depende del peso de su hijo, por lo que
debe preguntarle al mdico qu cantidad debe darle.
No administre aspirina ni medicinas con aspirina a nios menores de 18 aos. En los
nios, la aspirina puede causar un problema grave llamado sndrome de Reye.
Tampoco debe darles sprays para la garganta ni caramelos para la tos, ya que no
son ms efectivos para el dolor que los caramelos duros. Adems, los sprays para la
garganta pueden provocar una reaccin alrgica.
Otros tratamientos En el caso de nios de ms de 3 o 4 aos, comer caramelos
duros o paletas podra resultar til. En el caso de nios de entre 6 y 8 aos, es
posible que sientan alivio si hacen grgaras con agua salada.

Cundo puede regresar mi hijo a la escuela? Si la causa del dolor de garganta de


su hijo fue un virus, puede volver a la escuela en cuanto se sienta mejor. Si tiene fiebre,
debe quedarse en casa hasta al menos 24 horas despus de que la fiebre desaparezca.

Cmo puedo evitar que mi hijo vuelva a tener dolor de garganta? Lave las manos
de su hijo frecuentemente con agua y jabn. Esa es una de las mejores maneras de
prevenir el contagio de la infeccin. Tambin puede usar alcohol en gel, pero debe
asegurarse de que el gel cubra toda la superficie de la mano de su hijo.

Trate de ensearle a su hijo otras maneras de prevenir el contagio de grmenes, por


ejemplo, no tocarse la cara despus de estar con una persona enferma.

Ms informacin sobre este tema

Educacin para el paciente: Infeccin en la garganta por estreptococo en nios


(Conceptos Bsicos)
Educacin para el paciente: Tos, escurrimiento nasal y el resfriado comn (Conceptos
Bsicos)
Educacin para el paciente: Cmo administrarle a su hijo medicinas de venta sin receta
(Conceptos Bsicos)

Patient education: Sore throat in children (Beyond the Basics)


Patient education: The common cold in children (Beyond the Basics)

Todos los artculos se actualizan a medida que se descubre nueva evidencia y culmina
nuestro proceso de evaluacin por homlogos

LARINGOTRAQUEITIS
Croup: Clinical features, evaluation, and diagnosis

Author:
Charles R Woods, MD, MS
Section Editors:
Gregory Redding, MD
Anna H Messner, MD
Sheldon L Kaplan, MD
Deputy Editor:
Carrie Armsby, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: May 10, 2016.

INTRODUCTION Croup is a respiratory illness characterized by inspiratory stridor,


cough, and hoarseness. These symptoms result from inflammation in the larynx and
subglottic airway. A barking cough is the hallmark of croup among infants and young
children, whereas hoarseness predominates in older children and adults. Although croup
usually is a mild and self-limited illness, significant upper airway obstruction, respiratory
distress, and, rarely, death, can occur.

The clinical features, evaluation, and diagnosis of croup will be discussed here. The
management of croup is discussed separately. (See "Croup: Approach to
management" and "Croup: Pharmacologic and supportive interventions".)

DEFINITIONS The term croup has been used to describe a variety of upper respiratory
conditions in children, including laryngitis, laryngotracheitis, laryngotracheobronchitis,
bacterial tracheitis, or spasmodic croup [1]. These terms are defined below. In the past, the
term croup also has been applied to laryngeal diphtheria (diphtheritic or membranous
croup), which is discussed separately. (See "Epidemiology and pathophysiology of
diphtheria" and "Clinical manifestations, diagnosis, and treatment of diphtheria".)

Throughout this review, the term croup will be used to refer to laryngotracheitis.
Laryngotracheobronchitis, laryngotracheobronchopneumonitis, bacterial tracheitis, and
spasmodic croup are designated specifically as such.

Laryngitis Laryngitis refers to inflammation limited to the larynx and manifests


itself as hoarseness [2]. It usually occurs in older children and adults and, similar to
croup, is frequently caused by a viral infection. The etiology, management, and
evaluation of other causes of hoarseness are discussed in detail separately.
(See "Common causes of hoarseness in children" and "Hoarseness in children:
Evaluation".)
Laryngotracheitis (croup) Laryngotracheitis (croup) refers to inflammation of the
larynx and trachea [2]. Although lower airway signs are absent, the typical barking
cough will be present.
Laryngotracheobronchitis (LTB) LTB occurs when inflammation extends into the
bronchi, resulting in lower airway signs (eg, wheezing, crackles, air trapping,
increased tachypnea) and sometimes more severe illness than laryngotracheitis
alone [2]. This term commonly is used interchangeably with laryngotracheitis, and the
entities are often indistinct clinically. Further extension of inflammation into the lower
airways results in laryngotracheobronchopneumonitis, which sometimes can be
complicated by bacterial superinfection. Bacterial superinfection can be manifest as
pneumonia, bronchopneumonia, or bacterial tracheitis.
Bacterial tracheitis Bacterial tracheitis (also called bacterial croup) describes
bacterial infection of the trachea, resulting in a thick, purulent exudate, which causes
symptoms of upper airway obstruction (picture 1). The bronchi and lungs are typically
involved as well (ie, bacterial tracheobronchitis). Bacterial tracheitis may occur as a
complication of viral respiratory infections (usually those which manifest themselves
as LTB or laryngotracheobronchopneumonitis) or as a primary bacterial infection.
(See "Bacterial tracheitis in children: Clinical features and diagnosis".)
Spasmodic croup Spasmodic croup is characterized by the sudden onset of
inspiratory stridor at night, short duration (several hours), and sudden cessation [2].
This is often in the setting of a mild upper respiratory infection, but without fever or
inflammation. A striking feature of spasmodic croup is its recurrent nature, hence the
alternate descriptive term, "frequently recurrent croup." Because of some clinical
overlap with atopic diseases, it is sometimes referred to as "allergic croup."
Eosinophilic esophagitis may be an underlying issue in a subset of children with
spasmodic croup [3]. (See "Clinical manifestations and diagnosis of eosinophilic
esophagitis".)
Atypical croup Atypical croup may be defined as recurrent episodes of croup-like
symptoms occurring beyond the typical age range for viral croup (ie, six months to
three years) or recurrent episodes that do not appear to be simple "spasmodic croup"
[4]. We consider "spasmodic croup" to be distinct from "atypical croup," although the
terms are sometimes used interchangeably.

ETIOLOGY Croup is usually caused by viruses. Bacterial infection may occur


secondarily, as described above.

Parainfluenza virus type 1 is the most common cause of acute laryngotracheitis, especially
the fall and winter epidemics [5-7]. Parainfluenza type 2 sometimes causes croup
outbreaks, but usually with milder disease than type 1. Parainfluenza type 3 causes
sporadic cases of croup that often are more severe than those due to types 1 and 2. In
multicenter surveillance of children <5 years who were hospitalized with febrile or acute
respiratory illnesses, 43 percent of children with confirmed parainfluenza infection were
diagnosed with croup [8]. Croup was the most common discharge diagnosis for children
with confirmed parainfluenza 1 (42 percent) and parainfluenza 2 (48 percent) infections but
was only diagnosed in 11 percent of children with confirmed parainfluenza 3 infections.
Compared with types 1 to 3, infection caused by parainfluenza virus type 4 is less likely to
be associated with stridor and croup in children [9].

The microbiology, pathogenesis, and epidemiology of parainfluenza infections are


discussed separately. (See "Parainfluenza viruses in children".)

A number of other viruses that typically cause lower respiratory tract disease also can
cause upper respiratory tract symptoms, including croup, as described below [7].

Respiratory syncytial virus and adenoviruses are relatively frequent causes of croup.
The laryngotracheal component of disease is usually less significant than that of the
lower airways. (See "Respiratory syncytial virus infection: Clinical features and
diagnosis", section on 'Clinical manifestations' and "Epidemiology and clinical
manifestations of adenovirus infection", section on 'Clinical presentation'.)
Human coronavirus NL63 (HCoV-NL63), first identified in 2004, has been implicated
in croup and other respiratory illnesses [10-12]. The prevalence of HCoV-NL63 varies
geographically. (See "Coronaviruses", section on 'Respiratory'.)
Measles is an important cause of croup in areas where measles remains prevalent.
(See "Measles: Clinical manifestations, diagnosis, treatment, and prevention".)
Influenza virus is a relatively uncommon cause of croup. However, children
hospitalized with influenzal croup tend to have longer hospitalization and greater risk
of readmission for relapse of laryngeal symptoms than those with parainfluenzal
croup. (See "Seasonal influenza in children: Clinical features and diagnosis", section
on 'Pneumonia and respiratory tract complications'.)
Rhinoviruses, enteroviruses (especially Coxsackie types A9, B4, and B5, and
echovirus types 4, 11, and 21), and herpes simplex virus are occasional causes of
sporadic cases of croup that are usually mild. (See "Clinical manifestations and
diagnosis of enterovirus and parechovirus infections" and "Epidemiology, clinical
manifestations, and pathogenesis of rhinovirus infections".)
Metapneumoviruses cause primarily lower respiratory tract disease similar to RSV,
but upper respiratory tract symptoms have been described in some patients [13].
(See "Human metapneumovirus infections".)

Croup also may be caused by bacteria. Mycoplasma pneumoniae has been associated
with mild cases of croup. In addition, secondary bacterial infection may occur in children
with laryngotracheitis, laryngotracheobronchitis, or laryngotracheobronchopneumonitis.
The most common secondary bacterial pathogens include Staphylococcus
aureus, Streptococcus pyogenes, and Streptococcus pneumoniae [1].

EPIDEMIOLOGY Croup most commonly occurs in children 6 to 36 months of age. It is


seen in younger infants (as young as three months) and in preschool children, but it is
uncommon in children >6 years old [1,14]. It is more common in boys, with a male:female
ratio of approximately 1.4:1 [1,14-16].

Family history of croup is a risk factor for croup and recurrent croup. In a case-control
study, children whose parents had a history of croup were 3.2 times as likely to have an
episode of croup and 4.1 times as likely to have recurrent croup as children with no
parental history of croup [17]. Parental smoking, a well-recognized risk factor for
respiratory tract infections in children, does not appear to increase the risk of croup
[17,18]. (See "Secondhand smoke exposure: Effects in children", section on 'Respiratory
symptoms and illness'.)

Most cases of croup occur in the fall or early winter, with the major incidence peaks
coinciding with parainfluenza type 1 activity (often in October) and minor peaks occurring
during periods of respiratory syncytial virus or influenza virus activity. (See "Respiratory
syncytial virus infection: Clinical features and diagnosis", section on
'Seasonality' and "Seasonal influenza in children: Clinical features and diagnosis", section
on 'Influenza activity'.)

Emergency department (ED) visits for croup are most frequent between 10:00 PM and
4:00 AM [19]. However, children seen for croup between noon and 6:00 PM are more likely
to be admitted to the hospital [5,20]. A morning peak between 7:00 AM and 11:00 AM in ED
visits for croup also has been noted [16].

Hospital admissions for croup have declined steadily since the late 1970s. In an analysis
of data from the National Hospital Discharge Surveys from 1979 through 1997, the
estimated number of annual hospitalizations for croup decreased from 48,900 to 33,500
[6]. Estimates of annual hospitalization rates for croup caused by parainfluenza virus types
1 to 3 from 1994 to 1997 were 0.4 to 1.1 per 1000 children for children younger than one
year and 0.24 to 0.61 per 1000 children for children between one and four years.
Approximately one-half of these hospitalizations were attributed to parainfluenza type 1.

In a six-year (1999 to 2005) population-based study, 5.6 percent of children with a


diagnosis of croup in the ED required hospital admission. Among those discharged home,
4.4 percent had a repeat ED visit within 48 hours [16].

PATHOGENESIS The viruses that cause croup typically infect the nasal and
pharyngeal mucosal epithelia initially and then spread locally along the respiratory
epithelium to the larynx and trachea.

The anatomic hallmark of croup is narrowing of the subglottic airway, the portion of the
larynx immediately below the vocal folds. The cricoid cartilage of the subglottis is a
complete cartilaginous ring, unlike the tracheal rings which are horseshoe shaped.
Because it is a complete ring, the cricoid cannot expand, causing significant airway
narrowing whenever the subglottic mucosa becomes inflamed. In addition to this "fixed"
obstruction, dynamic obstruction of the extrathoracic trachea below the cartilaginous ring
may occur when the child struggles, cries, or becomes agitated. The dynamic obstruction
occurs as a result of the combination of high negative pressure in the distal extrathoracic
trachea and the floppiness of the tracheal wall in children.

Laryngoscopic evaluation of patients during acute laryngotracheitis shows redness and


swelling in the area just below the vocal folds. In severe cases, the subglottic airway may
be reduced to a diameter of 1 to 2 mm. In addition to mucosal edema and swelling,
fibrinous exudates and, occasionally, pseudomembranes can build up on the tracheal
surfaces and contribute to airway narrowing. The vocal folds and laryngeal tissues also
can become swollen, and cord mobility may be impaired [2,21-23]. Autopsy studies in
children with laryngotracheitis show infiltration of histiocytes, lymphocytes, plasma cells,
and neutrophils into edematous lamina propria, submucosa, and adventitia of the larynx
and trachea [24-26].

In spasmodic or recurrent croup, findings on direct laryngoscopy may demonstrate


noninflammatory edema [21]. This suggests that there is no direct viral involvement of the
tracheal epithelium. In a retrospective case series of 197 children with recurrent croup who
underwent endoscopy at a single center from 2002 to 2012, 21 percent had evidence of
subglottic stenosis and 20 percent had abnormal esophageal biopsies (including evidence
of reflux esophagitis, eosinophilic esophagitis, and candidal esophagitis) [3]. Children with
subglottic stenosis tended to be younger compared with those without (mean age 35
versus 58 months). In another case series of 103 children with recurrent croup who
underwent endoscopy at a single center from 2004 to 2013, 44 percent had a history of
prior intubation, subglottic stenosis, or a previous airway procedure [27]. Other common
underlying conditions included asthma (64 percent), gastroesophageal reflux (60 percent),
and seasonal allergies (48 percent). Endoscopy was normal in 65 percent of the children
in this series; 9 percent of children had moderate to severe findings (including subglottic
stenosis, cyst, and hemangioma).

Patients with bacterial tracheitis have a bacterial superinfection that causes thick pus to
develop within the lumen of the subglottic trachea (picture 1). Ulcerations,
pseudomembranes, and microabscesses of the mucosal surface occur. The supraglottic
tissues usually are normal. (See "Bacterial tracheitis in children: Clinical features and
diagnosis", section on 'Pathogenesis and pathology'.)

Host factors Only a small fraction of children with a parainfluenza viral infection
develop overt croup. This suggests that host (or genetic) factors play a role in the
pathogenesis. Host factors that may contribute to the development of croup include
functional or anatomic upper airway narrowing, variations in immune response, and
predisposition to atopy [16].

Underlying host factors that predispose to clinically significant narrowing of the upper
airway include:
Congenital anatomic narrowing of the airway, such as subglottic stenosis due to an
elliptical cricoid cartilage [4]. (See "Congenital anomalies of the larynx", section on
'Laryngeal atresia'.)
Hyperactive airways, perhaps aggravated by atopy or gastroesophageal reflux, as
suggested in some children with spasmodic croup or recurrent croup [28-30].
Acquired airway narrowing from a post-intubation subglottic cyst or stenosis, or
rarely from respiratory tract papillomas (human papillomavirus). Subglottic
hemangiomas (picture 2 and picture 3) grow in the first few months of life and the
patients will typically present with symptoms mimicking croup (ie, stridor and a
barking cough). (See "Congenital anomalies of the larynx", section on
'Cysts' and "Congenital anomalies of the larynx", section on 'Subglottic
hemangiomas'.)

The potential role of the immune response was demonstrated in studies that demonstrated
increased production of parainfluenza virus-specific immunoglobulin E (IgE) and increased
lymphoproliferative response to parainfluenza virus antigen, and diminished histamine-
induced suppression of lymphocyte transformation responses to parainfluenza virus in
children with parainfluenza virus and croup compared with those with parainfluenza virus
without croup [31,32].

CLINICAL PRESENTATION The clinical presentation of croup depends upon the


specific croup syndrome and the degree of upper airway obstruction. Although croup
usually is a mild and self-limited illness, specific features of the history and physical
examination identify children who are seriously ill or at risk for rapid progression of
disease. (See 'Evaluation' below.)

Laryngotracheitis Laryngotracheitis typically occurs in children three months to three


years of age [2]. The onset of symptoms is usually gradual, beginning with nasal
discharge, congestion, and coryza. Symptoms generally progress over 12 to 48 hours to
include fever, hoarseness, barking cough, and stridor. Respiratory distress increases as
upper airway obstruction becomes more severe. Rapid progression or signs of lower
airway involvement suggests a more serious illness. Cough usually resolves within three
days [33]; other symptoms may persist for seven days with a gradual return to normal [2].
Deviation from this expected course should prompt consideration of diagnoses other than
laryngotracheitis. (See 'Differential diagnosis' below.)

The degree of upper airway obstruction is evident on physical examination, as described


below. In mild cases, the child is hoarse and has nasal congestion. There is minimal, if
any, pharyngitis. As airway obstruction progresses, stridor develops, and there may be
mild tachypnea with a prolonged inspiratory phase. The presence of stridor is a key
element in the assessment of severity. Biphasic stridor (stridor heard on both inspiration
and expiration) at rest is a sign of significant upper airway obstruction. As upper airway
obstruction progresses, the child may become restless or anxious. (See 'Severity
assessment' below.)
When airway obstruction becomes severe, suprasternal, subcostal, and intercostal
retractions may be seen. Breath sounds can be diminished. Agitation, which generally is
accompanied by increased inspiratory effort, exacerbates the subglottic narrowing by
creating negative pressure in the airway. This can lead to further respiratory distress and
agitation.

Hypoxia and cyanosis can develop, as can respiratory fatigue from sustained increased
respiratory effort. High respiratory rates also tend to correlate with the presence of
hypoxia. Without intervention, the hypoxia or fatigue can rarely lead to death.

Spasmodic croup Spasmodic croup also occurs in children three months to three
years of age [2]. In contrast to laryngotracheitis, spasmodic croup always occurs at night;
the duration of symptoms is short, often with symptoms subsiding by the time of
presentation for medical attention; and the onset and cessation of symptoms are abrupt.
Fever is typically absent, but mild upper respiratory tract symptoms (eg, coryza) may be
present. Episodes can recur within the same night and for two to four successive evenings
[34]. A striking feature of spasmodic croup is its recurrent nature, hence the alternate
descriptive term, "frequently recurrent croup." There may be a familial predisposition to
spasmodic croup, and it may be more common in children with a family history of allergies
[28].

Early in the clinical course, spasmodic croup may be difficult to distinguish from
laryngotracheitis. As the course progresses, the episodic nature of spasmodic croup and
relative wellness of the child between attacks differentiate it from classic croup, in which
the symptoms are continuous.

Although the initial presentation can be dramatic, the clinical course is usually benign.
Symptoms are almost always relieved by comforting the anxious child and administering
humidified air. Rarely, children may benefit from treatment with
corticosteroids and/or nebulized epinephrine [35]. Other therapies generally are not
indicated. (See "Croup: Approach to management".)

Recurrent croup A child who has had recurrent episodes of classic viral croup may
have an underlying condition that predisposes him or her to develop clinically significant
narrowing of the upper airway. Recurrent episodes of croup-like symptoms occurring
outside the typical age range for "viral croup" (ie, six months to three years) and recurrent
episodes that do not appear to be simple "spasmodic croup" should raise suspicion for
airway lesions, gastroesophageal reflux or eosinophilic esophagitis, or atopic conditions
[3,4,27,36-39]. (See 'Differential diagnosis' below.)

In children who have recurrent croup without clear predisposing factors as noted above,
radiographic evaluation, laryngoscopy, bronchoscopy, and/or esophagoscopy may be
warranted. (See 'Host factors' above and 'Imaging' below.)
Bacterial tracheitis Bacterial tracheitis may present as a primary or secondary
infection [40]. In primary infection, there is acute onset of symptoms of upper airway
obstruction with fever and toxic appearance. In secondary infection, there is marked
worsening during the clinical course of viral laryngotracheitis, with high fever, toxic
appearance, and increasing respiratory distress secondary to tracheal obstruction from
purulent secretions. In both of these presentations, signs of lower airway disease, such as
crackles and wheezes, may be present. However, the upper airway obstruction is the more
clinically significant manifestation [2,41]. (See "Bacterial tracheitis in children: Clinical
features and diagnosis", section on 'Clinical features'.)

EVALUATION

Overview The evaluation of children with suspected croup has several objectives,
including prompt identification of patients with significant upper airway obstruction or at risk
for rapid progression of upper airway obstruction. In addition, there are some conditions
with presentations similar to that of croup that require specific
evaluations and/or interventions; these too must be promptly identified. (See 'Differential
diagnosis' below.)

During the evaluation, efforts should be made to make the child as comfortable as
possible. The increased inspiratory effort that accompanies anxiety and fear in young
children can exacerbate subglottic narrowing, further diminishing air exchange and
oxygenation. (See 'Pathogenesis' above.)

Rapid assessment and initial management Rapid assessment of general


appearance (including the presence of stridor at rest), vital signs, pulse oximetry, airway
stability, and mental status is necessary to identify children with severe respiratory
distress and/or impending respiratory failure (table 1). Children who have severe
respiratory distress require immediate pharmacologic treatment (including administration
of nebulized epinephrine and systemic or nebulized corticosteroids) and respiratory
support. (See "Croup: Approach to management", section on 'Moderate to severe
croup' and "Croup: Approach to management", section on 'Respiratory care'.)

Once treatment is under way and the child is more stable, the remainder of the evaluation
can proceed.

History The history should include a description of the onset, duration, and progression
of symptoms. Factors that are associated with increased severity of illness include:

Sudden onset of symptoms


Rapidly progressing symptoms (ie, symptoms of upper airway obstruction after
fewer than 12 hours of illness)
Previous episodes of croup
Underlying abnormality of the upper airway
Medical conditions that predispose to respiratory failure (eg, neuromuscular
disorders)

Aspects of the history that are helpful in distinguishing croup from other causes of acute
upper airway obstruction include [1,42]:

Fever The absence of fever from onset of symptoms to the time of presentation is
suggestive of spasmodic croup or a noninfectious etiology (eg, subglottic cyst,
subglottic hemangioma).
Barking cough The classic physical finding in a patient with subglottic narrowing is
a barky seal-like cough.
Hoarseness Hoarseness may be present in croup, particularly in older children,
whereas hoarseness is not a typical finding in epiglottitis or foreign body aspiration.
Difficulty swallowing Difficulty swallowing may occur in acute epiglottitis. Rarely, a
large, ingested foreign body may lodge in the upper esophagus, where it distorts and
narrows the upper trachea, thus mimicking the croup syndrome (including barking
cough and inspiratory stridor).
Drooling Drooling may occur in children with peritonsillar or retropharyngeal
abscesses, retropharyngeal cellulitis, and epiglottitis. In an observational study,
drooling was present in approximately 80 percent of children with epiglottitis, but only
10 percent of those with croup [42].
Throat pain Complaints of dysphagia and sore throat are more common in children
with epiglottitis than croup (approximately 60 to 70 percent versus <10 percent) [42].

The differential diagnosis of croup is discussed in greater detail below. (See 'Differential
diagnosis' below.)

Examination The objectives of the examination of the child with croup include
assessment of severity of upper airway obstruction and exclusion of other infectious and
non-infectious causes of acute upper airway obstruction, both of which are necessary in
making management decisions.

The initial examination often can be accomplished by observing the child in a comfortable
position with the caretaker. Every effort should be made to measure the child's weight and
vital signs.

Aspects of the examination that are helpful in assessing the degree of upper airway
obstruction and severity of illness include:

Overall appearance Is the child comfortable and interactive, anxious and quiet, or
obtunded? Is there stridor at rest? Stridor at rest is a sign of significant upper airway
obstruction. Children with significant upper airway obstruction may prefer to sit up and
lean forward in a "sniffing" position (neck is mildly flexed, and head is mildly
extended). This position tends to improve the patency of the upper airway.
Quality of the voice Does the child have a hoarse or diminished cry? Is the voice
muffled? A muffled "hot potato" voice is suggestive of epiglottitis, retropharyngeal
abscess, or peritonsillar abscess.
Degree of respiratory distress Signs of respiratory distress include tachypnea,
hypoxemia, and increased work of breathing (intercostal, subcostal, or suprasternal
retractions; nasal flaring; grunting; use of accessory muscles)
Tidal volume Does there appear to be good chest expansion with inspiration,
indicating adequate air entry?
Lung examination Are there abnormal respiratory sounds during inspiration or
expiration? Inspiratory stridor indicates upper airway obstruction, whereas expiratory
wheezing is a sign of lower airway obstruction. If there is stridor, is it present at rest or
only with agitation? As discussed above, stridor at rest is a sign of significant upper
airway obstruction. Stridor will be more obvious on auscultation, since the inspiratory
noise is transmitted through the chest. The presence of crackles (rales) also suggests
lower respiratory tract involvement (eg, laryngotracheobronchitis,
laryngotracheobronchopneumonitis, or bacterial tracheitis).
Assessment of hydration status Decreased oral intake and increased insensible
losses from fever and tachypnea may result in dehydration. (See "Clinical
assessment and diagnosis of hypovolemia (dehydration) in children".)

These aspects of the examination are often used in clinical scoring systems to evaluate
the severity of illness and/or in making decisions regarding the need for hospital
admission. (See 'Severity assessment' below and "Croup: Approach to management",
section on 'Observation and disposition'.)

Components of the examination that are useful in distinguishing croup from other causes
of acute upper airway obstruction include [42,43]:

Preferred posture Children with epiglottitis usually prefer to sit up in the "tripod" or
"sniffing position" (picture 4A-B).
Examination of the oropharynx for the following signs:
Cherry red, swollen epiglottis, suggestive of epiglottitis.
Pharyngitis, typically minimal in laryngotracheitis, may be more pronounced in
epiglottitis or laryngitis.
Excessive salivation, suggestive of acute epiglottitis, peritonsillar abscess,
parapharyngeal abscess or retropharyngeal abscess.
Diphtheritic membrane.
Tonsillar asymmetry or deviation of the uvula suggestive of peritonsillar
abscess.
Midline or unilateral swelling of the posterior pharyngeal wall suggestive of
retropharyngeal abscess.
Concerns have been raised about safety of examining the pharynx in children
with upper airway obstruction and possible epiglottitis since such efforts have
been reported to precipitate cardiorespiratory arrest. However, in two series,
each including more than 200 patients with epiglottitis or viral croup, direct
examination of the oropharynx was not associated with sudden clinical
deterioration [40,44].
Examination of the cervical lymph nodes, which can be enlarged in patients with
retropharyngeal or peritonsillar abscesses.
Other physical findings may be present, depending on the particular inciting virus.
As an example, rash, conjunctivitis, exudative pharyngitis, and adenopathy are
suggestive of adenovirus infection.
Otitis media (acute or with effusion) may be present as a primary viral or secondary
bacterial process.

The differential diagnosis of croup is discussed in greater detail below. (See 'Differential
diagnosis' below.)

Severity assessment The severity of croup is often determined by clinical scoring


systems. There are a number of validated croup scoring systems. The Westley croup
score has been the most extensively studied (table 1) (calculator 1) [45]. Severity is
determined by the presence or absence of stridor at rest, the degree of chest wall
retractions, air entry, the presence or absence of pallor or cyanosis, and the mental status:

Mild croup (Westley croup score of 2) Children with mild croup have no stridor
at rest (although stridor may be present when upset or crying), a barking cough,
hoarse cry, and either no, or only mild, chest wall/subcostal retractions [1,43,46].
Moderate croup (Westley croup score of 3 to 7) Children with moderate croup
have stridor at rest, have at least mild retractions, and may have other symptoms or
signs of respiratory distress, but little or no agitation [1,43,46].
Severe croup (Westley croup score of 8) Children with severe croup have
significant stridor at rest, although the loudness of the stridor may decrease with
worsening upper airway obstruction and decreased air entry [1,43,46]. Retractions
are severe (including indrawing of the sternum) and the child may appear anxious,
agitated, or pale and fatigued.
Impending respiratory failure (Westley croup score of 12) Croup occasionally
results in significant upper airway obstruction with impending respiratory failure,
heralded by the following signs [1,43,46]:
Fatigue and listlessness
Marked retractions (although retractions may decrease with increased
obstruction and decreased air entry)
Decreased or absent breath sounds
Depressed level of consciousness
Tachycardia out of proportion to fever
Cyanosis or pallor

Prompt recognition and treatment of children with severe croup are paramount.
(See "Croup: Approach to management", section on 'Moderate to severe croup'.)

Imaging

Indications Radiographic confirmation of acute laryngotracheitis is not required in the


vast majority of children with croup. Radiographic evaluation of the chest and/or upper
trachea is indicated if the diagnosis is in question, the course is atypical, an inhaled or
swallowed foreign body is suspected (although the majority are not radio-opaque), croup is
recurrent, and/or there is a failure to respond as expected to therapeutic interventions.
(See 'Differential diagnosis' below and "Croup: Approach to management".)

Findings In children with croup, a posterior-anterior chest radiograph demonstrates


subglottic narrowing, commonly called the "steeple sign" (image 1). The lateral view may
demonstrate overdistention of the hypopharynx during inspiration [47] and subglottic
haziness (image 2). The epiglottis should have a normal appearance.

In contrast, the lateral radiograph in virtually all children with epiglottitis demonstrates
swelling of the epiglottis, sometimes called the "thumb sign" (image 3). (See "Epiglottitis
(supraglottitis): Clinical features and diagnosis", section on 'Radiographic features'.)

The lateral radiograph in children with bacterial tracheitis may demonstrate only
nonspecific edema or intraluminal membranes and irregularities of the tracheal wall (image
4) [48].

Laboratory studies Laboratory studies, which are rarely indicated in children with
croup, are of limited diagnostic utility, but may help guide management in more severe
cases.

Blood tests The white blood cell (WBC) count can be low, normal, or elevated; WBC
counts >10,000 cells/microL are common. Neutrophil or lymphocyte predominance may be
present on the differential [49,50]. The presence of a large number of band-form
neutrophils is suggestive of primary or secondary bacterial infection. Croup is not
associated with any specific alterations in serum chemistries.

Microbiology Confirmation of etiologic diagnosis is not necessary for most children


with croup, since croup is a self-limited illness that usually requires only symptomatic
therapy. When an etiologic diagnosis is necessary, viral culture and/or rapid diagnostic
tests that detect viral antigens are performed on secretions from the nasopharynx or
throat. (See 'Etiologic diagnosis' below.)

DIAGNOSIS
Clinical diagnosis The diagnosis of croup is clinical, based on the presence of a
barking cough and stridor, especially during a typical community epidemic of one of the
causative viruses. (See 'Etiology' above.)

Neither radiographs nor laboratory tests are necessary to make the diagnosis. However,
radiographs may be helpful in excluding other causes if the diagnosis is in question.
(See 'Differential diagnosis' below.)

Etiologic diagnosis Although not typically required in most cases of croup,


identification of a specific viral etiology may be necessary to make decisions regarding
isolation for patients requiring hospitalization or for public health/epidemiologic monitoring
purposes. Testing for influenza is indicated if the results will influence decisions regarding
treatment, prophylaxis of contacts, or performance of other diagnostic tests; laboratory
confirmation should not delay the initiation of antiviral therapy for influenza when clinical
and seasonal considerations are compatible with influenza as the potential etiology of
croup. (See "Seasonal influenza in children: Prevention and treatment with antiviral drugs",
section on 'Timing of treatment' and "Seasonal influenza in children: Clinical features and
diagnosis", section on 'Whom to test'.)

Diagnosis of a specific viral etiology can be made by viral culture of secretions from the
nasopharynx or throat. Rapid tests that detect viral antigens in these secretions are
commercially available for many respiratory viruses. The diagnosis of specific viral
infections is discussed in detail in individual topic reviews:

Parainfluenza (see "Parainfluenza viruses in children", section on 'Diagnosis')


Influenza (see "Seasonal influenza in children: Clinical features and diagnosis",
section on 'Diagnosis')
Respiratory syncytial virus (see "Respiratory syncytial virus infection: Clinical
features and diagnosis", section on 'Laboratory diagnosis')
Adenovirus (see "Diagnosis, treatment, and prevention of adenovirus infection",
section on 'Diagnostic tests of choice for different adenovirus syndromes')
Measles (see "Measles: Clinical manifestations, diagnosis, treatment, and
prevention", section on 'Diagnosis')
Enteroviruses (see "Clinical manifestations and diagnosis of enterovirus and
parechovirus infections", section on 'Laboratory diagnosis')
Metapneumovirus (see "Human metapneumovirus infections", section on
'Diagnosis')
Coronavirus (see "Coronaviruses", section on 'Diagnosis')

In addition, multiplex tests, which assess the presence of multiple agents at the same time,
and polymerase chain reaction-based tests are becoming more widely available [51].

DIFFERENTIAL DIAGNOSIS The differential diagnosis of croup includes other causes


of stridor and/or respiratory distress. The primary considerations are those with acute
onset, particularly those that may rapidly progress to complete upper airway obstruction,
and those that require specific therapy. Underlying anatomic anomalies of the upper
airway also must be considered, since they may contribute to more severe disease.
(See 'Host factors' above.)

Important considerations include [1,14]:

Acute epiglottitis Epiglottitis, which is rare in the era of vaccination


against Haemophilus influenzae type b, is distinguished from croup by the absence of
barking cough and the presence of anxiety that is out of proportion to the degree of
respiratory distress. Onset of symptoms is rapid, and because of the associated
bacteremia, the child is highly febrile, pale, toxic, and ill-appearing. Because of the
swollen epiglottis, the child will have difficulty swallowing and is often drooling. The
children usually prefer to sit up and seldom have observed cough [42]. Epiglottitis
occurs infrequently, and there is no predominant etiologic pathogen. (See "Epiglottitis
(supraglottitis): Clinical features and diagnosis".)
Peritonsillar, parapharyngeal, or retropharyngeal abscesses Children with
deep neck space abscesses, cellulitis of the cervical prevertebral tissues, or other
painful infections of the pharynx may present with fever, drooling, neck stiffness,
lymphadenopathy, and varying degrees of toxicity. Barking cough is usually absent.
(See "Peritonsillar cellulitis and abscess", section on
'Presentation' and "Retropharyngeal infections in children", section on 'Presentation'.)
Foreign body In foreign body aspiration, there often is a history of the sudden
onset of choking and symptoms of upper airway obstruction in a previously healthy
child. If an inhaled foreign body lodges in the larynx, it will produce hoarseness and
stridor. If a large foreign body is swallowed, it may lodge in the upper esophagus,
resulting in distortion of the adjacent soft extrathoracic trachea, producing a barking
cough and inspiratory stridor. Ingestion of a non-obstructive but subsequently erosive
foreign bodies such as a button battery may produce stridor more remote from the
time of ingestion that persist or recur [52]. (See "Airway foreign bodies in
children" and "Foreign bodies of the esophagus and gastrointestinal tract in children".)
Allergic reaction or acute angioneurotic edema Allergic reaction or acute
angioneurotic edema has rapid onset without antecedent cold symptoms or fever. The
primary manifestations are swelling of the lips and tongue, urticarial rash, dysphagia
without hoarseness, and sometimes inspiratory stridor [1,14]. There may be a history
of allergy or a previous attack. (See "An overview of angioedema: Clinical features,
diagnosis, and management", section on 'Clinical features'.)
Upper airway injury Injury to the airway from smoke or thermal or chemical burns
should be evident from the history. The child typically does not have fever or a viral
prodrome. (See "Inhalation injury from heat, smoke, or chemical irritants".)
Anomalies of the airway Hoarseness and stridor caused by anomalies of the
upper airway (eg, laryngeal webs, laryngomalacia, vocal cord paralysis, congenital
subglottic stenosis, subglottic hemangioma) and laryngeal papillomas have a more
chronic course with absence of fever and symptoms of upper respiratory tract illness,
unless the presentation is due to exacerbation of airway narrowing from the impact of
a concomitant viral infection. Subglottic hemangioma (picture 2 and picture 3) should
be considered in any young infant who presents with a barking cough and no other
signs of a viral infection. Often these infants will respond temporarily to the usual
treatment for croup (steroids and nebulized epinephrine) however the symptoms will
recur within a few days of completion of treatment. (See "Assessment of stridor in
children" and "Common causes of hoarseness in children" and "Congenital anomalies
of the larynx".)
Other potential mimickers of croup Other potential mimickers of croup include
bronchogenic cyst (which can cause airway compression) and early Guillain-Barr
syndrome (involvement of the laryngeal nerve may cause vocal cord paralysis)
[53,54]. (See "Congenital anomalies of the intrathoracic airways and
tracheoesophageal fistula", section on 'Bronchogenic cyst' and "Guillain-Barr
syndrome in children: Epidemiology, clinical features, and diagnosis", section on
'Clinical features' and "Common causes of hoarseness in children", section on 'Vocal
fold paralysis'.)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Croup (The Basics)")


Beyond the Basics topic (see "Patient education: Croup in infants and children
(Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

The term croup has been used to describe a variety of upper respiratory conditions
in children, including laryngitis, laryngotracheitis, laryngotracheobronchitis, bacterial
tracheitis, or spasmodic croup. (See 'Definitions' above.)
Croup is usually caused by viruses. Bacterial infection may occur secondarily.
Parainfluenza virus type 1 is the most common cause of croup; other causes include
respiratory syncytial virus and influenza virus. (See 'Etiology' above.)
Croup most commonly occurs in children 6 to 36 months of age. Most cases occur
in the fall or early winter. (See 'Epidemiology' above.)
Host factors that may contribute to the development of croup include functional or
anatomic susceptibility to upper airway narrowing. (See 'Pathogenesis' above.)
The clinical presentation of croup depends upon the specific croup syndrome and
the degree of upper airway obstruction. (See 'Clinical presentation' above.)
The onset of symptoms in laryngotracheitis is gradual, beginning with nasal irritation,
congestion, and coryza. Fever, hoarseness, barking cough, and stridor usually
develop during the next 12 to 48 hours. Rapid progression or signs of lower airway
involvement suggest a more serious illness. (See 'Laryngotracheitis' above.)
The onset of symptoms in spasmodic croup is sudden and always occurs at night.
Fever is typically absent, but mild upper respiratory tract symptoms may be present.
(See 'Spasmodic croup' above.)
Bacterial tracheitis (picture 1 and image 4) may present acutely or as marked
worsening during the course of an antecedent viral upper respiratory infection.
Clinical manifestations of bacterial tracheitis include fever, toxic appearance, and
severe respiratory distress. (See 'Bacterial tracheitis' above and "Bacterial tracheitis
in children: Clinical features and diagnosis".)
The objectives of the evaluation of the child with croup include assessment of
severity (table 1) (calculator 1) and exclusion of other causes of upper airway
obstruction. (See 'Overview' above and 'Severity assessment' above.)
Rapid assessment of general appearance, vital signs, pulse oximetry, airway
stability, and mental status are necessary to identify children with severe respiratory
distress and/or impending respiratory failure. (See 'Rapid assessment and initial
management' above.)
The history should include a description of the onset, duration, and progression of
symptoms, and ascertain whether there are any underlying conditions that predispose
to a more severe course. (See 'History' above.)
Aspects of the examination that are useful in assessing the severity of upper airway
obstruction include overall appearance (including the presence of stridor at rest or
only with agitation), quality of voice, work of breathing, tidal volume and air entry, and
the presence of wheezing. (See 'Examination' above.)
The diagnosis of croup is clinical, based upon the presence of a barking cough and
stridor. Neither radiographs nor laboratory tests are necessary to make the diagnosis.
However, radiographs may be helpful in excluding other causes if the diagnosis is in
question. (See 'Diagnosis' above.)
The differential diagnosis of croup includes other causes of stridor and/or respiratory
distress. The primary considerations are those with acute onset, particularly those
that may rapidly progress to complete upper airway obstruction, and those that
require specific therapy. Important considerations include acute epiglottitis,
peritonsillar and retropharyngeal abscesses, foreign body aspiration, acute
angioneurotic edema, upper airway injury, and congenital anomalies of the upper
airway. (See 'Differential diagnosis' above.)
Use of UpToDate is subject to the Subscription and License Agreement.

Croup: Approach to management

Author:
Charles R Woods, MD, MS
Section Editors:
Sheldon L Kaplan, MD
Anna H Messner, MD
Deputy Editor:
Carrie Armsby, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Aug 02, 2016.

INTRODUCTION Croup (laryngotracheitis) is a respiratory illness characterized by


inspiratory stridor, barking cough, and hoarseness. It typically occurs in children six
months to three years of age and is chiefly caused by parainfluenza virus. (See "Croup:
Clinical features, evaluation, and diagnosis".)

Most children with croup who seek medical attention have a mild, self-limited illness and
can be successfully managed as outpatients. The clinician must be able to identify children
with mild symptoms, who can be safely managed at home, and those with moderate to
severe croup or rapidly progressing symptoms, who require full evaluation and possible
treatment in the office or emergency department setting. (See 'Severity assessment' below
and 'Outpatient treatment' below.)

There is no definitive treatment for the viruses that cause croup. Pharmacologic therapy is
directed toward decreasing airway edema, and supportive care is directed toward the
provision of respiratory support and the maintenance of hydration. Corticosteroids and
nebulized epinephrine are the cornerstones of therapy; their use is supported by
substantial clinical evidence. (See 'Initial treatment' below and "Croup: Pharmacologic and
supportive interventions".)

The approach to the management of croup will be discussed below. The clinical features
and evaluation of croup, and the evidence supporting the use of the pharmacologic and
supportive interventions included below are discussed separately. (See "Croup: Clinical
features, evaluation, and diagnosis" and "Croup: Pharmacologic and supportive
interventions".)

SEVERITY ASSESSMENT This initial step in the management of a child with croup is
assessing severity of illness. The first contact with the healthcare system may occur by
phone and the healthcare provider must be able to distinguish children with more severe
symptoms who need immediate medical attention from those who can be managed at
home. (See 'Telephone triage' below.)

When the child is seen in the office or emergency department, croup severity is assessed
by examining the child and using a clinical scoring system. (See 'Croup severity
score' below.)

Telephone triage When assessing patients by phone, the healthcare provider must
distinguish children who need immediate medical attention or further evaluation from those
who can be managed at home. Children who need further evaluation include those who
have:

Stridor at rest
Rapid progression of symptoms (ie, symptoms of upper airway obstruction after less
than 12 hours of illness)
Inability to tolerate oral fluids
Underlying known airway abnormality (eg, subglottic stenosis, subglottic
hemangioma, previous intubation)
Previous episodes of moderate to severe croup
Medical conditions that predispose to respiratory failure (eg, neuromuscular
disorders or bronchopulmonary dysplasia)
Parental concern that cannot be relieved by reassurance
Prolonged symptoms (more than three to seven days) or an atypical course
(perhaps indicating an alternative diagnosis) (see "Croup: Clinical features,
evaluation, and diagnosis", section on 'Differential diagnosis')

Patients who are assessed by phone and determined to have mild symptoms and none of
the above indications for further evaluation can be managed at home. (See 'Home
treatment' below.)

Croup severity score There are a number of validated croup scoring systems. The
Westley croup score has been the most extensively studied (table 1) (calculator 1) [1].
Severity is determined by the presence or absence of stridor at rest, the degree of chest
wall retractions, air entry, the presence or absence of pallor or cyanosis, and the mental
status:

Mild croup (Westley croup score of 2) Children with mild croup have no stridor at
rest (although stridor may be present when upset or crying), a barking cough, hoarse
cry, and either no, or only mild, chest wall/subcostal retractions [2-4]. (See 'Mild
croup' below.)
Moderate croup (Westley croup score of 3 to 7) Children with moderate croup
have stridor at rest, have at least mild retractions, and may have other symptoms or
signs of respiratory distress, but little or no agitation [2-4]. (See 'Moderate to severe
croup' below.)
Severe croup (Westley croup score of 8) Children with severe croup have
significant stridor at rest, although the loudness of the stridor may decrease with
worsening upper airway obstruction and decreased air entry [2-4]. Retractions are
severe (including indrawing of the sternum) and the child may appear anxious,
agitated, or pale and fatigued. Prompt recognition and treatment of children with
severe croup are paramount. (See 'Moderate to severe croup' below.)
Impending respiratory failure (Westley croup score of 12) Croup occasionally
results in significant upper airway obstruction with impending respiratory failure,
heralded by the following signs [2,4,5]:
Fatigue and listlessness
Marked retractions (although retractions may decrease with increased
obstruction and decreased air entry)
Decreased or absent breath sounds
Depressed level of consciousness
Tachycardia out of proportion to fever
Cyanosis or pallor
Patients who present to an office clinic with severe croup or signs and symptoms of
impending respiratory failure should be transported via emergency medical services
to an emergency department for management. (See 'Moderate to severe
croup' below.)

MILD CROUP Children with mild symptoms (Westley croup score of 2 (table 1)
(calculator 1)) should be treated symptomatically with humidity, fever reduction, and oral
fluids. Many such children can be managed by phone, provided that none of the criteria for
further evaluation described above are present. (See 'Telephone triage' above.)

Home treatment The caregivers of children with mild croup who are managed at home
should be instructed in provision of supportive care including mist, antipyretics, and
encouragement of fluid intake.

In acute situations and for short periods of time, caregivers may try sitting with the child in
a bathroom filled with steam generated by running hot water from the shower to improve
symptoms. This may help reassure parents that "something" is being done to reverse the
symptoms, and anecdotal evidence supports some benefit with this measure.

Exposure to cold night air also may lessen symptoms of mild croup, although this has
never been systematically studied. If parents or caregivers wish to use humidifiers at
home, only those that produce mist at room temperature should be used to avoid the risk
of burns from steam or the heating element.
Instructions should be provided to the caregivers regarding when to seek medical
attention, including watching for [2]:

Stridor at rest
Difficulty breathing
Pallor or cyanosis
Severe coughing spells
Drooling or difficulty swallowing
Fatigue
Worsening course
Fever (>38.5C)
Prolonged symptoms (longer than seven days)
Suprasternal retractions

Caregivers also should be provided with some guidance regarding when it is safe for them
to drive the child to the emergency department; emergency medical services should
provide transportation for children who are severely agitated, pale or cyanotic, struggling to
breathe, or lethargic [2].

Patients who are managed at home should receive a follow-up phone call within 24 hours.

Outpatient treatment We suggest that children with mild croup who are seen in the
outpatient setting be treated with a single dose of oral dexamethasone (0.15 to
0.6 mg/kg, maximum dose 10 mg) (algorithm 1). Randomized controlled trials in children
with mild croup have demonstrated that treatment with a single dose of oral
dexamethasone reduces the need for reevaluation, shortens the duration of symptoms,
improves the child's sleep, and reduces parental stress [6,7]. (See "Croup: Pharmacologic
and supportive interventions", section on 'Dexamethasone'.)

An alternative approach is nonpharmacologic management with anticipatory guidance


about potential worsening and instructions on when to seek care or return for follow-up.

Treatment with nebulized epinephrine is not typically necessary for management of mild
croup.

Children with mild croup who are tolerating fluids and have not received
nebulized epinephrine can be sent home after specific follow-up (which may occur by
phone) has been arranged and the caregiver has received instructions regarding home
care and indications to seek medical attention as described above. (See 'Home
treatment' above.)

MODERATE TO SEVERE CROUP


Setting and pace of treatment The appropriate treatment setting depends upon the
severity of symptoms:

Children with moderate croup (Westley croup score 3 to 7; stridor at rest and mild to
moderate retractions, but no or little distress or agitation (table 1) (calculator 1))
should be evaluated in the emergency department or office (provided the office is
equipped to handle acute upper airway obstruction).
Children with severe croup (Westley croup score 8; stridor at rest and marked
retractions with agitation, lethargy, or cyanosis (table 1) (calculator 1)) should be
evaluated in the emergency department as they require aggressive therapy,
monitoring, and supportive care.

The child with severe croup must be approached cautiously, as any increase in anxiety
may worsen airway obstruction. The parent or caregiver should be instructed to hold and
comfort the child. Nebulized epinephrine should be added as quickly as possible, as
described below. In the meantime, healthcare providers should continuously observe the
child and be prepared to provide bag-mask ventilation and advanced airway techniques if
the condition worsens (algorithm 1). (See 'Initial treatment' below and 'Respiratory
care' below.)

Initial treatment Initial treatment of moderate to severe croup includes administration


of dexamethasone and nebulized epinephrine. Children with moderate to severe croup
should also receive supportive care including humidified air or oxygen, antipyretics, and
encouragement of fluid intake. (See 'Supportive care' below.)

We recommend administration of dexamethasone (0.6 mg/kg, maximum of 10 mg) in all


children with moderate to severe croup. Dexamethasone should be administered by the
least invasive route possible: oral if oral intake is tolerated, intravenous (IV) if IV access
has been established, or intramuscular (IM) if oral intake is not tolerated and IV access
has not been established. The oral preparation of dexamethasone (1 mg/mL) has an
unpleasant taste. The IV preparation is more concentrated (4 mg per mL) and can be
given orally mixed with syrup [2,8-10]. A single dose of nebulized budesonide (2 mg [2 mL
solution] via nebulizer) is an alternative option, particularly for children who are vomiting
[2,4,11].

The benefit of corticosteroids for moderate to severe croup have been demonstrated in a
meta-analysis of 24 trials that found improvement in croup scores six hours after
treatment, fewer return visits or readmissions, decreased length of stay in the emergency
department or hospital, and decreased epinephrine use [7]. (See "Croup: Pharmacologic
and supportive interventions", section on 'Glucocorticoids'.)

In addition to dexamethasone, we recommend nebulized epinephrine in all patients with


moderate to severe croup:
Racemic epinephrine is administered as 0.05 mL/kg per dose (maximum of 0.5 mL)
of a 2.25 percent solution diluted to 3 mL total volume with normal saline. It is given
via nebulizer over 15 minutes.
L-epinephrine is administered as 0.5 mL/kg per dose (maximum of 5 mL) of a
1:1000 dilution. It is given via nebulizer over 15 minutes.

The benefits of nebulized epinephrine have been demonstrated in a meta-analysis of eight


trials that found improvement in croup score 30 minutes post-treatment and shorter
hospital stay; there was no difference in effectiveness between racemic epinephrine and L-
epinephrine [12]. (See "Croup: Pharmacologic and supportive interventions", section on
'Nebulized epinephrine'.)

Observation and disposition Patients should be observed for three to four hours after
initial treatment. The need for additional intervention and/or admission to the hospital is
determined chiefly by the response to therapy with corticosteroids and
nebulized epinephrine. The majority of children with moderate croup have symptomatic
improvement after treatment with nebulized epinephrine and corticosteroids and can be
discharged home, whereas those with severe symptoms on presentation are more likely to
require hospitalization.

Discharge to home Patients who have a good response to initial treatment should be
observed for three to four hours after pharmacologic intervention (algorithm 1) [13-16].
Croup symptoms usually improve within 30 minutes of administration of
nebulized epinephrine, but may recur as the effects of epinephrine wear off (usually by two
hours) [17,18]. Children who have recurrence or worsening of moderate to severe
symptoms during the observation period should receive additional racemic epinephrine
and should be admitted to the hospital. (See 'Indications for hospital admission' below.)

After three to four hours of observation, children who remain comfortable may be
discharged home if they meet the following criteria [13-16]:

No stridor at rest
Normal pulse oximetry
Good air exchange
Normal color
Normal level of consciousness
Demonstrated ability to tolerate fluids by mouth
Caregivers understand the indications for return to care and would be able to return
if necessary

Before discharge, follow-up with the primary care provider should be arranged within the
next 24 hours. Instructions regarding home treatment should be provided. (See 'Home
treatment' above.)
Approximately 5 percent of children well enough for discharge from the emergency
department after receiving corticosteroids and nebulized epinephrine treatments are
expected to return for care [19]. Relapse within 24 hours is unlikely in those who have
minimal symptoms at the time of discharge [20].

Indications for hospital admission Patients with ongoing severe symptoms after
initial treatment should receive additional nebulized epinephrine and should be admitted to
the hospital. Nebulized epinephrine can be repeated every 15 to 20 minutes. The
administration of three or more doses within a two- to three-hour time period should
prompt initiation of close cardiac monitoring if this is not already underway.

Children with persistent moderate symptoms can be observed for at least four hours
before deciding whether they require hospital admission as the effect
of dexamethasone may not be apparent for several hours [2].

Indications for inpatient admission include [2,21]:

Severe croup with poor air entry, altered consciousness, or impending respiratory
failure
Moderate/severe croup with persistent or deteriorating respiratory distress after
treatment with nebulized epinephrine and corticosteroids
"Toxic" appearance or clinical picture suggesting serious secondary bacterial
infection
Need for supplemental oxygen
Severe dehydration

Additional factors that influence the decision regarding admission include [2,21]:

Young age, particularly younger than six months


Recurrent visits to the emergency department within 24 hours
Ability of the family to comprehend the instructions regarding recognition of features
that indicate the need to return for care
Ability of the family to return for care (eg, distance from home to care
site, weather/travel conditions)

Admission to the pediatric intensive care unit (PICU) is warranted if any of the following
are present:

Respiratory failure requiring endotracheal intubation


Persistent severe symptoms requiring frequent nebulized epinephrine dosing
Underlying conditions placing the child at high risk for progressive respiratory failure
(eg, neuromuscular disease or bronchopulmonary dysplasia)
Approximately 8 to 15 percent of children with croup presenting to the emergency
department require hospitalization; only 1 percent require admission to the PICU [19,22].

Inpatient management Children admitted to the hospital for management of croup


should receive close respiratory monitoring and supportive care.

Supportive care Supportive care for children hospitalized with moderate to severe
croup includes:

Fluids Administration of intravenous fluids may be necessary in some children.


Fever and tachypnea may increase fluid requirements, and respiratory difficulty may
prevent the child from achieving adequate oral intake. (See "Maintenance fluid
therapy in children".)
Fever control High fever can contribute to tachypnea and respiratory distress in
children with croup, and treatment with antipyretics can improve work of breathing
and insensible fluid losses.
Comfort Care must be taken to avoid provoking agitation or anxiety in children
with moderate to severe croup as this can worsen the degree of respiratory distress
and airway obstruction. Children with severe croup should be approached cautiously
and unnecessary invasive interventions should be avoided. The parent or caregiver
should be instructed to hold and comfort the child and to assist in care. The use of
sedatives or anxiolytics to reduce agitation is discouraged as this may cause
respiratory depression.

Respiratory care Respiratory support for children hospitalized with croup may include
the following:

Nebulized epinephrine Repeated doses of nebulized epinephrine may be


warranted for children with moderate to severe distress. It is not always required; one
study of 365 hospitalizations for croup found that only 49 percent required additional
nebulized epinephrine during the inpatient stay [23]. Nebulized epinephrine can be
repeated every 15 to 20 minutes. However, children who require frequent doses of
epinephrine (eg, more frequently than every one to two hours) should
be admitted/transferred to an intensive care unit for close cardiopulmonary
monitoring. (See "Croup: Pharmacologic and supportive interventions", section on
'Nebulized epinephrine'.)
Supplemental oxygen Oxygen should be administered to children who are
hypoxemic (oxygen saturation of <92 percent in room air). Supplemental oxygen
should be humidified to decrease drying effects on the airways, since drying may
impede the physiologic removal of airway secretions via mucociliary and cough
mechanisms. (See "Continuous oxygen delivery systems for infants, children, and
adults".)
Mist Humidified air is frequently used in the treatment of croup, although a meta-
analysis of three trials evaluating the use of humidified air in croup found only
marginal improvement in croup scores [24]. Mist therapy may provide a sense of
comfort and reassurance to both the child and family; however, if the child is instead
agitated by the mist, it should be discontinued. (See "Croup: Pharmacologic and
supportive interventions", section on 'Mist therapy'.)
Heliox Heliox is a mixture of helium (70 to 80 percent) and oxygen (20 to 30
percent). Heliox may decrease the work of breathing in children with croup by
reducing turbulent airflow. A meta-analysis of three trials concluded that while there is
evidence to suggest a short-term benefit of heliox, a larger trial is needed before
recommendations regarding the use of heliox in children with croup can be made [25].
While the evidence from these trials does not suggest a large benefit from Heliox to
support its routine use in the management of croup, in patients with severe symptoms
who are at risk for respiratory failure, it may be used in an attempt to avoid the need
for intubation. An important limitation of heliox use is the low fractional concentration
of inspired oxygen (FiO2) in the gas mixture, which may not be adequate for children
with hypoxia. (See "Croup: Pharmacologic and supportive interventions", section on
'Heliox'.)
Intubation The need for intubation should be anticipated in children with
progressive respiratory failure so that the procedure can be performed in a controlled
setting if possible. Intubation can be challenging due to the narrowed subglottic
airway and should be performed with the assistance of a skilled provider (ie, an
anesthesiologist or otolaryngologist). Neuromuscular blocking agents should be
avoided unless the ability to provide bag-mask ventilation has been demonstrated. An
endotracheal tube that is 0.5 to 1 mm smaller than would typically be used should be
placed. (See 'Croup severity score' above and "Emergency endotracheal intubation in
children", section on 'Endotracheal tube'.)
Endotracheal intubation is rarely required for management of croup. In a large study
at one institution, less than 1 percent of children admitted to the hospital for croup
required intubation [22].

Repeated corticosteroid dosing Repeat doses of corticosteroids are not necessary


on a routine basis and may have adverse effects. Moderate to severe symptoms that
persist for more than a few days should prompt investigation for other causes of airway
obstruction. (See "Croup: Pharmacologic and supportive interventions", section on
'Repeated dosing' and "Croup: Clinical features, evaluation, and diagnosis", section on
'Differential diagnosis' and "Assessment of stridor in children".)

Monitoring Monitoring should include close observation of mental status and


respiratory status, including monitoring for stridor, cyanosis, air entry, and retractions.
Pulse oximetry monitoring is useful to detect hypoxia; however, it is not a sensitive tool for
assessing the severity of croup [21].

Infection control Children who are admitted to the hospital with croup should be
managed with contact precautions (ie, gown and gloves for contact), particularly if
parainfluenza or respiratory syncytial virus is the suspected etiology. If influenza is
suspected, droplet isolation measures (ie, respiratory mask within three feet) also should
be followed. (See "Infection prevention: Precautions for preventing transmission of
infection".)

Discharge criteria Children who require hospital admission may be discharged when
they meet the following criteria:

No stridor at rest
Normal pulse oximetry in room air
Good air exchange
Normal color
Normal level of consciousness
Demonstrated ability to tolerate fluids by mouth

Atypical course Children admitted for croup typically remain in the hospital for less
than 36 hours [23]. The child who does not show improvement as expected (over the
course of one to two days) may have an underlying airway abnormality or may be
developing a complication of croup. Further evaluation with radiographs of the soft tissues
of the neck, or consultation with otolaryngology, may be warranted. A biphasic illness with
poor response to nebulized epinephrine in conjunction with high fever and toxic
appearance should prompt consideration of bacterial tracheitis (picture 1) [2]. (See "Croup:
Clinical features, evaluation, and diagnosis", section on 'Differential
diagnosis' and "Bacterial tracheitis in children: Clinical features and diagnosis".)

FOLLOW-UP Any patient who was admitted to the hospital, received


nebulized epinephrine, or had a prolonged outpatient visit should have follow-up
scheduled with the primary care provider within 24 hours or as soon as can be arranged.
Although some children may continue to have mild to moderate symptoms at the time of
follow-up, there are no studies that support the routine use of corticosteroid therapy
beyond 24 hours.

Follow-up should continue until the child's symptoms have begun to resolve. The child
whose symptoms do not resolve over the course of approximately seven days may have
an underlying airway abnormality or may be developing a complication of croup.
(See 'Atypical course' above.)

PROGNOSIS Symptoms of croup resolve in most children within three days, but may
persist for up to one week [26,27]. Approximately 8 to 15 percent of children with croup
require hospital admission [19,28], and among those, less than 1 percent require
intubation [22]. Mortality is rare, occurring in <0.5 percent of intubated children [29].

Complications Complications of croup are uncommon. Children with moderate to


severe croup are at risk for hypoxemia (oxygen saturation <92 percent in room air) and
respiratory failure. Other complications include pulmonary edema, pneumothorax, and
pneumomediastinum [30]. These complications can be anticipated and managed by
aggressive monitoring and intervention in the medical setting. Out-of-hospital cardiac
arrest and death also have been reported [31].

Secondary bacterial infections may arise from croup. Bacterial tracheitis,


bronchopneumonia, and pneumonia occur in a small number of patients [5,27,32,33]. In
most instances, the child has been relatively stable or beginning to improve after several
days of illness, but then suddenly worsens, with higher or recurrent fever, increased (and
potentially productive) cough, and/or respiratory distress. (See "Bacterial tracheitis in
children: Clinical features and diagnosis", section on 'Clinical features' and "Community-
acquired pneumonia in children: Clinical features and diagnosis", section on 'Clinical
presentation'.)

Recurrent symptoms Approximately 5 percent of children treated for croup in the


outpatient setting have repeat visits for recurrent symptoms within seven days following
discharge [19]. Children who have recurrent episodes of classic viral croup may require
radiographic evaluation or bronchoscopy to evaluate for underlying airway abnormalities.
Recurrent episodes of croup-like symptoms occurring outside the typical age range for
"viral croup" (ie, six months to three years) and recurrent episodes that do not appear to
be simple "spasmodic croup" should raise suspicion for large airway lesions,
gastroesophageal reflux or eosinophilic esophagitis, or atopic conditions [34-39].
(See "Assessment of stridor in children" and "Croup: Clinical features, evaluation, and
diagnosis", section on 'Spasmodic croup'.)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Croup (The Basics)")


Beyond the Basics topics (see "Patient education: Croup in infants and children
(Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS


Children with croup should be seen in the office or emergency department if they
have stridor at rest, an underlying airway abnormality, previous episodes of moderate
to severe croup, underlying conditions that may predispose to respiratory failure,
rapid progression of symptoms, inability to tolerate fluids, prolonged symptoms, or an
atypical course. (See 'Telephone triage' above.)
Children with mild symptoms (ie, no stridor at rest and no respiratory distress) can
be managed at home. Families should be instructed in provision of supportive care
and indications to seek medical attention. (See 'Home treatment' above.)
We suggest that a single dose of oral dexamethasone (0.15 to 0.6 mg/kg) be used
when electing to treat children with mild croup who are seen in the outpatient setting
(algorithm 1) (Grade 2A). (See 'Outpatient treatment' above and "Croup:
Pharmacologic and supportive interventions", section on 'Dexamethasone'.)
Children with moderate croup (ie, stridor at rest with mild to moderate retractions)
should be evaluated in the office or emergency department, and those with severe
croup (stridor at rest with marked retractions and significant distress or agitation)
should be evaluated in the emergency department (table 1) (calculator 1). Children
with severe croup must be approached cautiously, as any increase in anxiety may
worsen airway obstruction. (See 'Moderate to severe croup' above.)
We recommend that children with moderate to severe croup be treated with a single
dose of dexamethasone (0.6 mg/kg, maximum of 10 mg) by the least invasive route
(algorithm 1) (Grade 1A). (See 'Initial treatment' above and "Croup: Pharmacologic
and supportive interventions", section on 'Glucocorticoids'.)
We recommend that children with moderate to severe croup be treated with
nebulized epinephrine (Grade 1A) in addition to dexamethasone (algorithm 1).
(See 'Initial treatment' above and "Croup: Pharmacologic and supportive
interventions", section on 'Nebulized epinephrine'.)
Racemic epinephrine is administered as 0.05 mL/kg per dose (maximum of 0.5
mL) of a 2.25 percent solution diluted to 3 mL total volume with normal saline. It
is given via nebulizer over 15 minutes.
L-epinephrine is administered as 0.5 mL/kg per dose (maximum of 5 mL) of a
1:1000 dilution. It is given via nebulizer over 15 minutes.
Nebulized epinephrine can be repeated every 15 to 20 minutes. The administration of
three or more doses within a two- to three-hour time period should prompt initiation of
close cardiac monitoring if this is not already underway.
Children with moderate to severe croup should be observed for three to four hours
after intervention. Those who improve may be discharged home. Children with
persistent or worsening symptoms during the observation period should be admitted
to the hospital. (See 'Discharge to home' above and 'Indications for hospital
admission' above.)
Management of children hospitalized for croup includes:
Supportive care with provision of intravenous fluids and fever reduction.
(See 'Supportive care' above.)
Respiratory care with repeated doses of nebulized epinephrine, as indicated by
respiratory distress, and administration of humidified air or oxygen, as indicated
by hypoxemia. (See 'Respiratory care' above.)
Monitoring for worsening respiratory distress. (See 'Monitoring' above.)
We suggest not using repeated doses of corticosteroids (Grade 2C). (See 'Repeated
corticosteroid dosing' above and "Croup: Pharmacologic and supportive
interventions", section on 'Repeated dosing'.)
Children who have moderate to severe symptoms that persist for more than a few
days, or recurring episodes of croup not associated with other manifestations of a
viral illness (no fever and/or rhinorrhea) should undergo investigation for other causes
of upper airway obstruction. (See 'Atypical course' above and 'Recurrent
symptoms' above and "Croup: Clinical features, evaluation, and diagnosis", section
on 'Differential diagnosis'.)
Children who received nebulized epinephrine, had a prolonged outpatient visit, or
were admitted to the hospital should have follow-up scheduled with the primary care
provider within 24 hours of discharge or as soon as follow-up can be arranged. Most
children with croup recover uneventfully. (See 'Follow-up' above
and 'Prognosis' above.)
Use of UpToDate is subject to the Subscription and License Agreement.

Croup: Pharmacologic and supportive interventions

Author:
Charles R Woods, MD, MS
Section Editors:
Sheldon L Kaplan, MD
Anna H Messner, MD
Deputy Editor:
Carrie Armsby, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Aug 02, 2016.

INTRODUCTION Croup (laryngotracheitis) is a respiratory illness characterized by


inspiratory stridor, barking cough, and hoarseness. It typically occurs in children six
months to three years of age and most commonly is caused by parainfluenza virus.
(See "Croup: Clinical features, evaluation, and diagnosis".)

The treatment of croup has changed significantly since the 1980s. Glucocorticoids and
nebulized epinephrine have become the cornerstones of therapy. Substantial clinical
evidence supports the efficacy of these interventions [1-5]. The impact also is evident in
the decrease in annual hospital admissions for croup in children in the United States
between 1979 to 1982 and 1994 to 1997 (from 2.8 to 2.1 per 1000 for children <1 year and
from 1.8 to 1.2 per 1000 children for children 1 to 4 years) [6].

Treatment of croup may involve a variety of pharmacologic and nonpharmacologic


interventions. It may occur entirely at home, or in the office, emergency department, or
hospital setting. Supportive and pharmacologic interventions will be discussed below. The
clinical features and evaluation of croup and the approach to management are discussed
separately. (See "Croup: Clinical features, evaluation, and diagnosis" and "Croup:
Approach to management".)

GLUCOCORTICOIDS Glucocorticoids provide long-lasting and effective treatment of


mild, moderate, and severe croup [3,7-9]. The anti-inflammatory actions of glucocorticoids
are thought to decrease edema in the laryngeal mucosa of children with croup.
Improvement is usually evident within six hours of administration but seldom is dramatic
[7,10].

Treatment with glucocorticoids at various doses and by various routes has been shown to
improve croup scores and to decrease unscheduled medical visits, length of stay in the
emergency department (ED) or hospital, and the use of epinephrine [7]. Among the
available glucocorticoids, dexamethasone has been used most frequently, is the least
expensive, has the longest duration of action, and is the easiest to administer.

Efficacy Intramuscular (IM), intravenous (IV), oral, and inhaled routes of administration
of glucocorticoids have been shown to be effective in croup of all levels of severity
[7,8]. Dexamethasone (oral or IM) and budesonide (inhaled) were the agents used in the
majority of studies. A systematic review included 24 trials (with collective enrollment of
2878 children) that objectively measured the effectiveness of glucocorticoid treatment for
croup compared with placebo [7]. Fourteen other trials compared different glucocorticoid
agents or different routes or dosages of the same agent [7]. Compared with treatment with
placebo, treatment with glucocorticoid was associated with:

Improvement in the croup score at six hours with a weighted mean difference of -1.2
(95% CI -1.6 to -0.8) and at 12 hours -1.9 (95% CI -2.4 to -1.3); at 24 hours this
improvement was no longer significant (-1.3, 95% CI -2.7 to 0.2).
Fewer return visits and/or (re)admissions (relative risk [RR] 0.50, 95% CI 0.3-0.7).
Decreased length of time spent in ED or hospital (weighted mean difference 12
hours, 95% CI 5-19 hours).
Decreased use of epinephrine (risk difference 10 percent; 95% CI 1-20 percent).
There were no significant differences in clinical efficacy between the routes or
agents, and the combination of oral or IM dexamethasone with
inhaled budesonide was not superior to either agent alone [11,12].
Another systematic review of eight randomized controlled trials compared the
administration of nebulized glucocorticoids with placebo. Children treated with nebulized
glucocorticoids were significantly more likely to show improvement in croup score at five
hours (combined RR 1.48, 95% CI 1.27-1.74) and significantly less likely to need hospital
admission (combined RR 0.56, 95% CI 0.42-0.75) [13].

Adverse effects The general safety of short-term administration of systemic


glucocorticoids for acute respiratory conditions in children, including croup, is supported by
several systematic reviews [14]. Few serious adverse effects have been reported in the
studies evaluating the efficacy of a single dose of glucocorticoids in croup [15]. However,
most of these studies were too small to sufficiently evaluate rare (<1 percent) adverse
effects [16,17].

The primary concern is potential risk of progressive viral infection or secondary bacterial
infection, which have been reported in patients who received glucocorticoid treatment over
several days [17], or received nebulized dexamethasone and had neutropenia [18]. These
complications have not been described in children who have received single doses of oral,
IM, or IV glucocorticoids for croup.

Glucocorticoid use may exacerbate active varicella and tuberculosis and should be
avoided in children with these infections and in those recently exposed to, and possibly
incubating, varicella [19,20]. (See "Clinical features of varicella-zoster virus infection:
Chickenpox".)

Administration of glucocorticoids may mask the presentation of steroid-responsive upper


airway lesions, such as hemangiomas, which also can present with stridor, particularly
during a viral upper respiratory tract infection [21]. (See "Infantile hemangiomas:
Epidemiology, pathogenesis, clinical features, and complications".)

Agents

Dexamethasone Dexamethasone can be given IM, IV, or orally and should generally
be administered via the least invasive route possible (orally if oral intake is tolerated, IV if
IV access has been established, or IM if oral intake is not tolerated and IV access has not
been established). Based on the available evidence, there do not appear to be clinically
significant differences in croup outcomes between IM and orally administered
dexamethasone [7].

The optimal dose of dexamethasone in children with croup is uncertain. In clinical trials,
doses ranging from 0.15 to 0.6 mg/kg have been shown to be effective [7]. For children
with moderate to severe croup (ie, Westley croup score of 3 (table 1)), we recommend a
single dose of 0.6 mg/kg (maximum 10 mg) [22]. Dexamethasone at this dose has proven
efficacy in croup as demonstrated in numerous clinical trials, including several high-quality
placebo-controlled trials [4,7,9,23]. Based on these data, we also suggest a dose of
0.6 mg/kg (maximum 10mg) for children with mild croup (ie, Westley croup score of 2
(table 1)); however, limited data suggest that lower doses (0.15 mg/kg to 0.4 mg/kg) may
be equally effective in patients with mild croup [7,24-27]. Nonpharmacologic management
is another reasonable alternative for patients with mild croup. (See "Croup: Approach to
management", section on 'Mild croup'.)

The oral liquid preparation of dexamethasone (1 mg per mL) has a foul taste. The IV
preparation is more concentrated (4 mg per mL) and can be given orally mixed with syrup
[11,28,29].

Studies of nebulized dexamethasone in children with croup have mixed results. One study
found nebulized dexamethasone to be less effective than oral dexamethasone in
preventing the need for subsequent treatment with glucocorticoid or epinephrine in
children with mild croup [23]. Another study found that treatment with nebulized
dexamethasone in children with moderate croup improved croup scores at four hours but
did not affect the rate of hospitalization [18]. In addition, two patients with neutropenia who
were treated with dexamethasone developed bacterial tracheitis.

Budesonide Nebulized budesonide has been shown to be more effective than placebo
and as effective as IM or oral dexamethasone for the treatment of croup [7,30]. However,
nebulized budesonide is more expensive and more difficult to administer than IM or oral
dexamethasone and is not routinely indicated in the treatment of croup. However,
nebulized budesonide may provide an alternative to IM or IV dexamethasone for children
with vomiting or severe respiratory distress [22]. In children with severe respiratory
distress, a single dose of budesonide may be mixed with epinephrine and administered
simultaneously. (See "Croup: Approach to management", section on 'Moderate to severe
croup'.)

Prednisolone Some authorities suggest that for children who are treated as
outpatients, oral prednisolone (2 mg/kg per day for three days) is an alternative to
oral dexamethasone [31]. The use of prednisolone in the treatment of croup has been
evaluated in a limited number of studies.

A 2011 meta-analysis of two trials [26,32] that compared a single dose of


oral dexamethasone (0.6 mg/kg or 0.15 mg/kg) with a single dose of
oral prednisolone (1 mg/kg) showed no difference in croup scores, but children
randomized to receive dexamethasone had fewer return visits and/or subsequent
admissions (9.6 versus 29.7 percent, RR 0.3, 95% CI 0.2-0.6) [7].

A subsequent randomized trial compared oral dexamethasone (0.6 mg/kg on the first day
followed by placebo on the next two days) with oral prednisolone (2 mg/kg per day for
three days) in 87 children with mild or moderate croup who were treated as outpatients
[31]. There were no differences between groups in additional health care visits (2 versus 7
percent [not significant]), duration of symptoms (2.8 versus 2.2 days), duration of nonbarky
cough (6.1 versus 5.9 days), nights with disturbed parental sleep (0.7 versus 1.2), or days
with stress (1.6 versus 1.4).

Another study of 70 children compared prednisolone (1 mg/kg every 12 hours) with


placebo in children with croup who were already intubated [8]. Children who received
prednisolone had a shorter median duration of intubation than those in the placebo group
(98 versus 138 hours). In addition, fewer children in the prednisolone group required
reintubation (5 versus 34 percent).

Prednisone The use of prednisone in the management of croup has not been
evaluated in clinical trials. However, it has equivalent potency to prednisolone and, in
theory, should have similar effects. Despite its lack of proven benefit, prednisone is widely
used in the outpatient management of croup [33].

If prednisone is to be used, it is important to administer a dose that is equivalent in


strength to the doses of glucocorticoids that have been better
studied. Dexamethasone has 6.67 times the glucocorticoid potency of prednisone
(4 mg/kg of prednisone = 0.6 mg/kg of dexamethasone; 2 mg/kg of prednisone =
0.3 mg/kg of dexamethasone; and 1 mg/kg of prednisone = 0.15 mg/kg of
dexamethasone). If choosing to use the higher dose (ie, 4 mg/kg of prednisone), the
volume required may be prohibitive given that the concentration of the oral solution of
prednisone is 1 mg/1 mL.

Betamethasone A pilot study compared the effectiveness of a single oral dose


of betamethasone (0.4 mg/kg) with a single dose of IM dexamethasone (0.6 mg/kg) in 52
children (six months to six years) with mild to moderate croup who were treated in the ED
[34]. Despite randomization, mean baseline croup scores were higher in the
dexamethasone group (3.6 versus 2). Croup scores declined significantly in both groups,
and there were no differences between groups in mean croup scores four hours after
treatment, rate of hospitalization, time to resolution of symptoms, need for additional
treatment, or number of return visits to the ED.

Repeated dosing The majority of clinical trials of oral and IM glucocorticoids in croup
have used a single dose. Repeat doses are not necessary on a routine basis. Although
repeat doses may be reasonable in the occasional child who has persistent symptoms,
they should be used with caution. The anecdotal cases of progression of viral illness and
secondary bacterial infection that have been reported with use of glucocorticoids for croup
occurred with repeated dosing over several days [35], or in neutropenic patients [18].
(See 'Adverse effects' above.)

Moderate to severe symptoms that persist for more than a few days should prompt
investigation for other causes of airway obstruction. (See "Croup: Clinical features,
evaluation, and diagnosis", section on 'Differential diagnosis'.)
NEBULIZED EPINEPHRINE The administration of nebulized epinephrine to patients
with moderate to severe croup often results in rapid improvement of upper airway
obstruction. Epinephrine constricts precapillary arterioles in the upper airway mucosa and
decreases capillary hydrostatic pressure, leading to fluid resorption and improvement in
airway edema [19]. Even a small increase in airway diameter can lead to significant clinical
improvement.

Benefits Several small randomized controlled trials and a meta-analysis have


demonstrated the benefit of racemic epinephrine compared with placebo in reducing the
croup scores 30 minutes after treatment in children in the emergency department (ED),
hospital, and intensive care unit (ICU) [1,36-38]. The magnitude of reduction in mean
croup score from baseline ranged from 2.2 to 3.6 at 20 to 30 minutes (compared with
approximately 1 in the placebo group). However, by 120 minutes, croup scores returned to
baseline or near baseline [1,37]. In one trial, treatment with intramuscular
(IM) dexamethasone and nebulized epinephrine was associated with decreased duration
of hospitalization compared with IM dexamethasone and placebo (-32 hours, 95% CI -59.1
to -4.9) [39,40].

Administration of epinephrine does not alter the natural history of croup in the short (>2
hours) or longer term (24 to 36 hours) [1,37,40].

In the studies described above, racemic epinephrine was administered either by


nebulization alone or by nebulization combined with intermittent positive pressure breaths
[1,36,37]. Another study compared these two methods of administration and found them to
be similarly effective [2].

Racemic versus L-epinephrine Racemic epinephrine, which is a 1:1 mixture of the D-


and L-isomers, was initially thought to produce fewer systemic side effects, such as
tachycardia and hypertension [19]. However, a randomized double-blind study comparing
racemic epinephrine and L-epinephrine in children with croup found no difference between
the two preparations in 30-minute croup score, heart rate, blood pressure, respiratory rate,
fraction of inspired oxygen, or oxygen saturation [41]. This finding is particularly important
outside of the United States, where racemic epinephrine is not readily available. Either
form of epinephrine is acceptable to use in the United States.

Dose

Racemic epinephrine is administered as 0.05 mL/kg per dose (maximum of 0.5 mL)
of a 2.25 percent solution diluted to 3 mL total volume with normal saline. It is given
via nebulizer over 15 minutes.
L-epinephrine is administered as 0.5 mL/kg per dose (maximum of 5 mL) of a
1:1000 dilution [41]. It is given via nebulizer over 15 minutes.
Nebulized epinephrine treatments may be repeated every 15 to 20 minutes if warranted by
the clinical course. Children who require repeated frequent dosing (eg, three or more
doses within two to three hours) to achieve stabilization of their respiratory function
generally should be admitted to an ICU or intermediate care setting (depending on the
severity of persisting signs).

There also does not appear to be any advantage of administering


nebulized epinephrine by use of intermittent positive pressure breathing versus simple
nebulization alone [40].

Precautions The clinical effects of nebulized epinephrine last for no more than two
hours. After the effects have worn off, symptoms may return to baseline (an apparent
worsening, sometimes referred to as the "rebound phenomenon"). Children who receive
even a single dose of nebulized epinephrine should be observed in the ED or hospital
setting for at least three to four hours after administration to ensure that symptoms do not
return to baseline.

Serious adverse effects from nebulized epinephrine are exceedingly rare. However, a case
of myocardial infarction in a child with croup who received three doses of racemic
epinephrine within 60 minutes has been reported [42]. Thus, it seems prudent to place
children who require ongoing epinephrine treatments more frequently than every one to
two hours on cardiac monitors (both because of the severity of illness and the potential
systemic impact of nebulized epinephrine). Continuous electrocardiographic monitoring (or
equivalent cardiac monitoring) also should be considered in these cases.

OXYGEN Oxygen is not known to have any direct impact on the subglottic edema or
airway narrowing, but should be administered to children who are hypoxemic (oxygen
saturation of <92 percent in room air) and/or in moderate to severe respiratory distress
[15,22]. Supplemental oxygen should be humidified to decrease drying effects on the
airways, since drying may impede the physiologic removal of airway secretions via
mucociliary and cough mechanisms. (See "Continuous oxygen delivery systems for
infants, children, and adults".)

Heliox Helium is inert, nontoxic, and of very low density. Heliox is a mixture of helium
(70 to 80 percent) and oxygen (20 to 30 percent). It can flow through airways with less
turbulence and resistance than pure oxygen. (See "Physiology and clinical use of heliox".)

Heliox decreases the work of respiration in children with croup and theoretically could be
used as a temporizing measure, to prevent the need for intubation while waiting for
glucocorticoids to decrease airway edema [43]. However, in clinical trials, heliox has not
definitively been shown to be more effective than humidified oxygen or
racemic epinephrine in reducing croup scores [44-46]. A 2013 systematic review found
only three methodologically limited trials (91 patients) evaluating heliox in children with
croup and concluded that a larger trial is needed before recommendations regarding the
use of heliox in children with croup can be made [46].

MIST THERAPY Humidified air is frequently used in the treatment of croup, although
there have been no studies supporting its efficacy in reducing symptoms [47]. Two
randomized trials (one comparing mist versus no mist and the other comparing no mist,
low humidity, and 100 percent humidity) among children brought to an emergency
department for croup demonstrated no significant change in croup scores from baseline
between the groups [48,49].

Although humidified air does not reduce subglottic edema, it may provide other benefits.
Inhalation of moist air, relative to dry air, may decrease drying of inflamed mucosal
surfaces and reduce inspissation of secretions [50]. In addition, a mist source may provide
a sense of comfort and reassurance to both the child and family [51-53]. In medical
settings, mist therapy may be provided by blow-by or saline nebulization treatments. Croup
tents should be avoided, since they can aggravate a child's anxiety and make vital signs
and other visual assessments of the child more difficult. Some guidelines recommend
against the use of mist therapy for children who are hospitalized with croup [22]. Certainly
if the child is agitated by the provision of mist, mist therapy should be discontinued.

OTHER THERAPIES

Antibiotics Antibiotics have no role in the routine management of uncomplicated croup,


since most cases are caused by viruses [15]. Antibiotics should be used only to treat
specific bacterial complications, such as tracheitis.

Antitussives Nonprescription antitussive agents are of unproven benefit for croup (or
other respiratory tract infections). Codeine, which is a more potent cough suppressant, can
alter the child's sensorium, making it difficult to follow the clinical course.

Decongestants Decongestants also are of unproven benefit for croup [15,22].

Sedatives The routine use of sedative agents in effort to improve airway obstruction by
relieving anxiety and apprehension is not recommended. Sedatives may treat the
symptom of agitation while masking the underlying causes of air hunger and hypoxia. They
also may decrease respiratory effort (and therefore croup scores), without improving
ventilation [15,54].

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Croup (The Basics)")


Beyond the Basics topic (see "Patient education: Croup in infants and children
(Beyond the Basics)")

SUMMARY

Treatment with glucocorticoids (oral, intramuscular [IM], intravenous, or nebulized)


has been shown to decrease croup scores, unscheduled medical visits, length of stay
in the emergency department or hospital, and the use of epinephrine. A single dose of
oral or IM dexamethasone is appropriate and adequate for most children.
(See 'Glucocorticoids' above and "Croup: Approach to management", section on
'Initial treatment'.)
Treatment with nebulized epinephrine results in rapid improvement of upper airway
obstruction, but the duration of effect is less than two hours. Racemic epinephrine
and L-epinephrine appear to be equally effective. (See 'Nebulized
epinephrine' above.)
Humidified air is frequently used as a supportive treatment for croup; however, there
have been no studies supporting its efficacy in reducing symptoms. (See 'Mist
therapy' above.)
Humidified oxygen should be administered to children who are hypoxemic and/or in
moderate to severe respiratory distress. (See 'Oxygen' above.)
Heliox has not definitively been shown to be more effective than humidified oxygen
or racemic epinephrine in reducing croup scores. (See 'Heliox' above.)
Antibiotics should be used only to treat specific bacterial complications of croup.
(See 'Antibiotics' above and "Croup: Approach to management", section on
'Complications'.)
Antitussives and decongestants are of unproven benefit in the management of
croup. Sedatives may decrease the work of breathing and improve agitation without
actually improving ventilation or addressing the underlying cause of agitation
(hypoxemia). (See 'Other therapies' above.)

BRONQUIOLITIS
Bronchiolitis in infants and children: Treatment, outcome, and prevention

Authors:
Pedro A Piedra, MD
Ann R Stark, MD
Section Editors:
George B Mallory, MD
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Feb 23, 2017.

INTRODUCTION Bronchiolitis, part of the spectrum of lower respiratory tract diseases,


is a major cause of illness and hospitalization in infants and children younger than two
years. The treatment, outcome, and prevention of bronchiolitis will be reviewed here. The
epidemiology, clinical features, and diagnosis of bronchiolitis and the treatment of
recurrent virus-induced wheezing in young children are discussed separately.
(See "Bronchiolitis in infants and children: Clinical features and diagnosis" and "Treatment
of recurrent virus-induced wheezing in young children".)

DEFINITION For the purposes of this topic review, bronchiolitis is broadly defined as a
clinical syndrome that occurs in children <2 years of age and is characterized by upper
respiratory symptoms (eg, rhinorrhea) followed by lower respiratory (eg,
small airway/bronchiole) infection with inflammation, which results in wheezing and or
crackles (rales). Bronchiolitis typically occurs with primary infection or reinfection with a
viral pathogen, but occasionally is caused by bacteria (eg, Mycoplasma pneumoniae). In
young children, the clinical syndrome of bronchiolitis may overlap with recurrent virus-
induced wheezing and acute viral-triggered asthma. The diagnosis of bronchiolitis, virus-
induced wheezing, and acute viral-triggered asthma are discussed separately.
(See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on
'Diagnosis' and "Virus-induced wheezing and asthma: An overview" and "Asthma in
children younger than 12 years: Initial evaluation and diagnosis" and "Asthma in children
younger than 12 years: Initial evaluation and diagnosis", section on 'Respiratory tract
infections'.)

SEVERITY ASSESSMENT Consensus definitions for severe bronchiolitis are lacking.


In general, we consider severe bronchiolitis to be indicated by any of the following:

Persistently increased respiratory effort (tachypnea; nasal flaring; intercostal,


subcostal, or suprasternal retractions; accessory muscle use; grunting) as assessed
during repeated examinations separated by at least 15 minutes
Hypoxemia (SpO2 <95 percent); SpO2 should be interpreted in the context of other
clinical signs, the state of the patient (eg, awake, asleep, coughing, etc), and altitude
Apnea
Acute respiratory failure

We consider nonsevere bronchiolitis to be indicated by the absence of all of the above.


However, the severity categories may overlap and clinical judgment is necessary to make
appropriate management decisions.

Repeated observations are necessary to adequately assess disease severity because


examination findings may vary substantially over time [1].

INDICATIONS FOR HOSPITALIZATION Although clinical practice varies widely [2-4],


hospitalization for supportive care and monitoring usually is indicated for infants and young
children with [5-7]:

Toxic appearance, poor feeding, lethargy, or dehydration


Moderate to severe respiratory distress, manifested by one or more of the following
signs: nasal flaring; intercostal, subcostal, or suprasternal retractions; respiratory rate
>70 breaths per minute; dyspnea; or cyanosis
Apnea
Hypoxemia with or without hypercapnia (arterial or capillary carbon dioxide tension
>45 mmHg); studies evaluating SpO2 (oxygen saturation) <95 percent as a predictor
of disease severity or progression among outpatient children with bronchiolitis have
inconsistent results [8,9]; nonetheless the authors of this topic use SpO2 <95 percent
on room air at sea level as a finding that may warrant admission (see 'Supplemental
oxygen' below)
Parents who are unable to care for them at home

Although age <12 weeks is a risk factor for severe or complicated disease, young age in
and of itself is not an indication for hospitalization. (See "Bronchiolitis in infants and
children: Clinical features and diagnosis", section on 'Risk factors for severe disease'.)

Hypoxemia is often used as a criterion for admission in infants without comorbid conditions
for severe disease. However, it should not be the only criterion. Observational studies
suggest that episodes of desaturation with mild to moderate respiratory distress are
common in infants with bronchiolitis and that detection of hypoxemia may be associated
with increased health care utilization (eg, supplemental oxygen, admission, increased
length of stay) but little or no acute benefit [4,10-12]. The effect of brief periods of
hypoxemia caused by bronchiolitis on the developing brain has not been adequately
addressed.

In an observational study, the families of 118 otherwise healthy infants (6 weeks to 12


months) who were born at >36 weeks' gestation and discharged home from the
emergency department with a diagnosis of acute bronchiolitis were provided with a
portable oxygen saturation monitor that recorded SpO2 but neither displayed saturation
values nor sounded alarms for threshold values [12]. Based on clinical characteristics at
discharge from the emergency department, these infants had mild to moderate
bronchiolitis that did not require hospitalization. Approximately two-thirds of infants had at
least one episode of SpO2 <90 percent for at least one minute; one-half had at least three
episodes; and 43 percent had SpO2 <90 percent continuously for 3 minutes. Episodes of
desaturation typically occurred during sleep or while feeding. The rates of unscheduled
medical visits and hospitalizations for bronchiolitis within 72 hours of discharge from the
emergency department were similar among infants with and without desaturations
(approximately 25 percent and <5 percent, respectively). Information beyond 72 hours
post-discharge was not collected, which is a limitation of the study.

NONSEVERE BRONCHIOLITIS

Overview of approach Infants and children with nonsevere bronchiolitis usually can be
managed in the outpatient setting, unless there are concerns about the caregivers' ability
to care for them at home. (See 'Indications for hospitalization' above.)

Supportive care and anticipatory guidance are the mainstays of management of nonsevere
bronchiolitis. Supportive care includes maintenance of adequate hydration, relief of
nasal congestion/obstruction, and monitoring for disease progression. (See 'Anticipatory
guidance' below and 'Follow-up' below.)

For immune competent infants and children with nonsevere bronchiolitis who are treated in
the office or emergency department, we do not routinely recommend pharmacologic
interventions because they lack proven benefit, increase the cost of care, and may have
adverse effects. Randomized trials, systematic reviews, and meta-analyses do not support
the benefits of bronchodilators (inhaled or oral) [13-18], glucocorticoids (inhaled or
systemic) [1,19-24], or leukotriene inhibitors [25]. Antibiotics are indicated only if there is
evidence of a coexisting bacterial infection. This approach is consistent with that of the
American Academy of Pediatrics, the National Institute for Care Excellence, and other
professional organizations [1,5,7,26]. (See 'Interventions that are not routinely
recommended' below.)

For infants and children with nonsevere bronchiolitis who are treated in the office or
emergency department, we suggest not routinely treating with nebulized hypertonic saline.
In a 2015 systematic review of randomized trials evaluating administration of hypertonic
saline in the emergency department, hypertonic saline reduced the rate of hospitalization
among children with bronchiolitis, but the evidence was of low quality [26].

Anticipatory guidance Education and anticipatory guidance are important aspects of


the management of bronchiolitis [5,26]. Components of education and anticipatory
guidance include:
Expected clinical course: Typical illness with bronchiolitis begins with upper
respiratory tract symptoms. Lower respiratory symptoms and signs develop on days 2
to 3, peak on days 3 to 5, and then gradually resolve over the course of two to three
weeks.
In a systematic review of four studies including 590 children with bronchiolitis who
were seen in outpatient settings and not treated with bronchodilators [16,27-29], the
mean time to resolution of cough ranged from 8 to 15 days [30]. Cough resolved in 50
percent of patients within 13 days and in 90 percent within 21 days. In a cohort of 181
children (not included in the systematic review), the median duration of caretaker-
reported symptoms was 12 days; approximately 20 percent continued to have
symptoms for at least three weeks, and 10 percent had symptoms for at least four
weeks [31].
Proper techniques for suctioning the nose (table 1). (See "Patient education:
Bronchiolitis (and RSV) in infants and children (Beyond the Basics)", section on 'Nose
drops or spray'.)
The need to monitor fluid intake and output; children with bronchiolitis may have
difficulty maintaining adequate hydration because of increased needs (related to fever
and tachypnea) and decreased intake (related to tachypnea and respiratory distress).
Avoidance of over-the-counter decongestants and cough medicines; these
medications have no proven benefit and may have serious adverse effects [32].
(See "The common cold in children: Management and prevention", section on 'Over-
the-counter medications'.)
Indications to return to medical care immediately: apnea, cyanosis, poor feeding,
new fever, increased respiratory rate and/or increased work of breathing (retractions,
nasal flaring, grunting), decreasing fluid intake (<75 percent of normal, no wet diaper
for 12 hours), exhaustion (eg, failure to respond to social cues, waking only with
prolonged stimulation) [5,26].
Strategies to prevent respiratory infection. (See 'Prevention' below.)

Follow-up Children with bronchiolitis who are not hospitalized should be monitored by
their clinician for progression and resolution of disease. Follow-up, usually within one to
two days, may occur by phone or at the office. The timing and method of follow-up depend
upon initial severity and duration of symptoms; patients who are seen in the first one to two
day of symptoms may worsen before they improve. Repeated clinical assessments of the
respiratory system (eg, respiratory rate, nasal flaring, retractions, grunting) may be
necessary to determine the course of the illness and to identify deteriorating respiratory
status. (See 'Anticipatory guidance' above.)

In children who do not improve as expected, chest radiographs may be helpful in excluding
other conditions in the differential diagnosis (eg, foreign body aspiration, heart failure,
vascular ring) [1]. (See "Bronchiolitis in infants and children: Clinical features and
diagnosis", section on 'Differential diagnosis' and 'Anticipatory guidance' above.)
SEVERE BRONCHIOLITIS Infants and children severe bronchiolitis usually require
treatment in the emergency department or inpatient setting. Supportive care and
anticipatory guidance are the mainstays of management of severe bronchiolitis. Supportive
care includes maintenance of adequate hydration, respiratory support, and monitoring for
disease progression. (See 'Severity assessment' above and 'Indications for
hospitalization' above.)

Emergency department management Emergency department management of severe


bronchiolitis centers on stabilization of respiratory and fluid status and determining the
appropriate setting for continuation of care (ie, observation unit, general inpatient ward, or
intensive care unit [ICU]).

Trial of inhaled bronchodilator We do not routinely suggest inhaled


bronchodilators for the management of the first episode of bronchiolitis in children.
However, a one-time trial of inhaled bronchodilators (albuterol [salbutamol]
or epinephrine) may be warranted for infants and children with severe bronchiolitis.
Children with severe disease or respiratory failure generally were excluded from trials
evaluating inhaled bronchodilators in children with bronchiolitis. (See 'Severity
assessment' above and 'Bronchodilators' below.)
Nebulized hypertonic saline For infants and children with severe bronchiolitis
who are treated in the emergency department, we suggest not routinely treating with
nebulized hypertonic saline. (See 'Nebulized hypertonic saline' below.)
Glucocorticoids We recommend not using glucocorticoids routinely in the
management of the first episode of bronchiolitis. (See 'Glucocorticoids' below.)

Inpatient management Inpatient management of severe bronchiolitis centers on


support of hydration and respiratory status as necessary. In addition to standard
precautions, children admitted with bronchiolitis should be placed on contact precautions.
(See "Infection prevention: Precautions for preventing transmission of infection", section
on 'Standard precautions' and "Infection prevention: Precautions for preventing
transmission of infection", section on 'Contact precautions'.)

Fluid management The fluid intake and output of infants and children with bronchiolitis
should be assessed regularly. Children with bronchiolitis may have difficulty maintaining
adequate hydration because of increased needs (related to fever and tachypnea) and
decreased intake (related to tachypnea and respiratory distress).

Exclusive parenteral fluid administration may be necessary to ensure adequate hydration


and avoid the risk of aspiration in infants and children who are hospitalized with
bronchiolitis and have moderate to severe respiratory distress (nasal flaring; intercostal,
subcostal, or suprasternal retractions; respiratory rate >70 breaths per minute; dyspnea; or
cyanosis) [1,33]. For children who can tolerate enteral feedings, strategies to maintain
hydration include small frequent feedings or orogastric or nasogastric feedings [5,34,35].
(See "Maintenance fluid therapy in children" and "Overview of enteral nutrition in infants
and children", section on 'Indications for enteral nutrition'.)

It is also important to monitor urine output. Plasma antidiuretic hormone levels rarely may
be elevated, leading to fluid retention and hyponatremia [36-38]. Fluid overload should be
avoided, since it may lead to pulmonary congestion. (See "Pathophysiology and etiology of
the syndrome of inappropriate antidiuretic hormone secretion (SIADH)", section on
'Pulmonary disease' and "Maintenance fluid therapy in children", section on 'Hospitalized
children'.)

Respiratory support Respiratory support for infants and young children with
bronchiolitis generally is provided in a stepwise fashion. Most children require nasal
suctioning. Supplemental oxygen is provided as necessary to maintain SpO2 >90 to 92
percent. Infants who are at risk for progression to respiratory failure often receive a trial of
heated humidified high-flow nasal cannula (HFNC) therapy and/or continuous positive
airway pressure (CPAP) before endotracheal intubation. However, initial endotracheal
intubation is more appropriate than HFNC or CPAP for children with hemodynamic
instability, intractable apnea, or loss of protective airway reflexes.

Nasal suctioning For children hospitalized with bronchiolitis, we suggest mechanical


aspiration of the nares as necessary to relieve nasal obstruction. Saline nose drops and
mechanical aspiration of nares may help to relieve partial upper airway obstruction in
infants and young children with respiratory distress or feeding difficulties. In a retrospective
cohort study of 740 infants (2 to 12 months) hospitalized with bronchiolitis, those who had
three or four lapses of mechanical suctioning of more than four hours had longer hospital
stay than those who had no lapses in suctioning (2.64 versus 1.62 days) [39].

There is little evidence to support routine frequent "deep" suctioning of the


oropharynx or larynx with a nasopharyngeal catheter [1]. Catheter suctioning of the
nasopharynx is traumatic and may produce edema and nasal obstruction. Catheter
suctioning of the oropharynx can induce cough, but the theoretic complication of
laryngospasm is not corroborated. In the retrospective cohort study of 740 patients
hospitalized with bronchiolitis, those who had >60 percent deep suctioning (ie, via
negative pressure vacuum system and nasopharyngeal catheter) during the first 24
hours of admission had longer hospital stay than patients with 60 percent deep
suctioning (2.35 versus 1.75 days) [39]. Prospective randomized studies are needed
to confirm this observation, which may be confounded by more frequent suctioning of
infants perceived to be sicker.

Supplemental oxygen Supplemental oxygen should be provided by nasal cannula,


face mask, or head box to maintain SpO2 above 90 to 92 percent [40].

Data are lacking to support the use of a specific SpO2 cutoff value. The American Academy
of Pediatrics practice guideline suggests SpO2 <90 percent as the threshold to start
supplemental oxygen [1]. However, variability in the accuracy of oximeters, and
concomitant fever, acidosis, or hemoglobinopathy favor the use of a higher cutoff value. In
a multicenter study comparing oxygen saturation simultaneously measured with pulse
oximetry (SpO2) and arterial blood gas (SaO2), the accuracy of pulse oximetry varied with
the range of oxygen saturation [41]. In the SpO2 range of 76 to 90 percent, pulse oximetry
tended to overestimate SaO2 (by a median of approximately 5 percent); in the SpO2 range
of 91 to 97 percent, SpO2 and SaO2 values were similar (median difference of 1 percent).

Close monitoring is required as supplemental oxygen is weaned, particularly for children


with hemodynamically significant heart disease, bronchopulmonary dysplasia, and
premature birth. (See "Continuous oxygen delivery systems for infants, children, and
adults".)

HFNC and CPAP Heated humidified high-flow nasal cannula (HFNC, also called high-
flow warm humidified oxygen) therapy and/or continuous positive airway pressure (CPAP)
are used to reduce the work of breathing, improve gas exchange, and avoid the need for
endotracheal intubation in children with bronchiolitis who are at risk for progression to
respiratory failure [42-44]. Successful therapy with HFNC or CPAP avoids the adverse
effects of endotracheal intubation (eg, laryngeal injury, ventilator-induced lung injury,
ventilator-associated pneumonia, narcotic dependence and withdrawal) [45].

HFNC and CPAP typically require care in an intensive or immediate care unit. However,
some institutions initiate HFNC in the emergency department or on the general ward [44].
A detailed discussion of critical care respiratory interventions for infants and young children
with bronchiolitis is beyond the scope of this review. General discussions of invasive and
noninvasive ventilation strategies for infants and children with respiratory failure are
provided separately. (See "Continuous oxygen delivery systems for infants, children, and
adults", section on 'High flow' and "Noninvasive ventilation for acute and impending
respiratory failure in children".)

HFNC therapy Our institutions use HFNC therapy to avoid endotracheal


intubation in infants and children with bronchiolitis who are at risk for respiratory
failure. In an open randomized trial and observational studies, HFNC has been
associated with decreased rates of endotracheal intubation [44,46-51].
HFNC is a well-tolerated noninvasive method of ventilatory support that permits high
inspired gas flows (4 to 8 L/min) with or without increased oxygen concentration
[52,53]. The increased flows are tolerated because the air is humidified; provision of
HFNC requires a special circuit it cannot be provided by simply turning up the flow
from the wall unit. Flow rates 6 L/min can generate positive expiratory pressures in
the range of 2 to 5 cm H2O. The size of the nasal cannula, which is determined by fit,
affects the size of the circuit and maximum amount of flow. For the treatment of
bronchiolitis in infants and children younger than two years, 8 L/min is generally the
maximum flow rate, but higher rates may be used (cannula size permitting) [54,55].
Contraindications to HFNC include abnormalities of the face or airway that preclude
an appropriate-fitting nasal cannula [56]. Relative contraindications include confusion
or agitation, vomiting, excessive secretions, and bowel obstruction. In an
observational study, nonresponse to HFNC was been associated with lower
pretherapy pH and higher pretherapy PCO2, highlighting the importance of early
initiation [57].
Complications of HFNC include abdominal distension, aspiration, barotrauma, and
pneumothorax (rare) [56]. However, the risk of pneumothorax is lower with HFNC
than with mechanical ventilation following endotracheal intubation.
Infants receiving HFNC who are clinically deteriorating may develop significant
respiratory acidosis (hypercapnia) despite high oxygen saturations (if they are
receiving supplemental O2). Oxygen saturation is a poor indicator of impending
respiratory failure, which is better indicated by marked retractions, decreased or
absent breath sounds, fatigue, and poor responsiveness to stimulation (eg, weak or
no cry). Blood gas analysis to assess ventilation (ie, PCO2 levels) may be warranted
in infants receiving HFNC who become more dyspneic and/or tachycardic.
In an open trial, 200 children <2 years who had moderately severe bronchiolitis and
required oxygen therapy were randomly assigned to early initiation of HFNC or
standard low-flow nasal cannula oxygen therapy, after which oxygen was weaned
according to a standardized protocol [51]. Early initiation of HFNC did not shorten the
median duration of oxygen therapy (20 versus 24 hours, hazard ratio [HR] 0.9, 95%
CI 0.7-1.2). However, HFNC was associated with avoidance of ICU admission among
20 of 32 children in the standard therapy group who received HFNC as rescue
therapy. These results support those of previous observational studies in which HFNC
was associated with decreased rates of intubation in children <24 months of age with
bronchiolitis who were admitted to a pediatric ICU compared with historical controls
[44,46-50]. A multicenter randomized trial is under way [58].
Additional trials are being conducted to determine the effectiveness and effect of
various flow rates on airway pressure, breathing patterns, and respiratory effort in
infants hospitalized with bronchiolitis [59-62]. Flow rates of 6 L/min appear to provide
positive pressure throughout the respiratory cycle, with positive end expiratory
pressures in the range of 2 to 5 cm H2O [56,60,63]. A multicenter trial is needed to
determine the optimal flow rate required for clinical benefit.
Continuous positive airway pressure Our institutions use continuous positive
airway pressure (CPAP) to avoid endotracheal intubation in infants and children with
bronchiolitis and respiratory failure, but less frequently than we use HFNC. CPAP can
decrease work of breathing and prevent endotracheal intubation in children with
progressive hypoxemia or hypercarbia [64]. In children who fail HFNC, CPAP may be
tried before endotracheal intubation. (See "Noninvasive ventilation for acute and
impending respiratory failure in children".)
Several observational and randomized studies suggest that CPAP improves
ventilation and oxygenation in infants with bronchiolitis and severe respiratory
distress, may avoid endotracheal intubation, and may be associated with decreased
length of stay in the ICU [45,65-73]. However, systematic reviews have found the
evidence regarding CPAP for bronchiolitis to be inconclusive because of
methodologic limitations in the existing studies [74,75]. Additional studies are
necessary to clarify the benefits of CPAP for infants with bronchiolitis who are
admitted to an ICU.

Endotracheal intubation Infants who have ongoing or worsening severe distress


despite a trial of HFNC and/or CPAP, those who have hypoxemia despite oxygen
supplementation, and those with apnea may require endotracheal intubation and
mechanical ventilation. Signs of impending respiratory failure in infants and young children
with bronchiolitis include marked retractions, decreased or absent breath sounds, fatigue,
and poor responsiveness to stimulation (eg, weak or no cry). Arterial or venous blood
gases obtained in infants with impending respiratory failure often reveal hypercapnia (ie,
carbon dioxide tension >55 mmHg [arterial sample] or >60 mmHg [venous sample]);
however, blood gases should not be used as the sole basis for deciding to intubate.
Endotracheal intubation is discussed separately. (See "Emergency endotracheal intubation
in children".)

Other therapies We do not routinely suggest chest physiotherapy, inhaled


bronchodilators, nebulized hypertonic saline, or leukotriene inhibitors (eg, montelukast) to
relieve lower airway obstruction in infants and children with first episode of bronchiolitis.
We do not recommend glucocorticoids in the management of a first episode of
bronchiolitis. (See 'Interventions that are not routinely recommended' below.)

Although we do not routinely suggest inhaled bronchodilators for the management of


bronchiolitis, a one-time trial of inhaled bronchodilators (albuterol [salbutamol]
or epinephrine) may be warranted for infants and children with bronchiolitis and severe
disease. Children with severe disease or respiratory failure generally were excluded from
trials evaluating inhaled bronchodilators in children with bronchiolitis. (See 'Severity
assessment' above and 'Bronchodilators' below.)

Chest physiotherapy may be warranted in children with comorbidities associated with


difficulty clearing respiratory secretions (eg, neuromuscular disorders, cystic fibrosis) [26].
However, in previously healthy children with bronchiolitis, chest physiotherapy has not
been shown to be useful [76]. (See 'Chest physiotherapy' below.)

There is little evidence to support the benefit of adjunctive glucocorticoids or surfactant in


the management of respiratory failure due to bronchiolitis. A meta-analysis of three studies
evaluating the use of systemic glucocorticoids in infants with bronchiolitis requiring
admission to the ICU found no overall effect on duration of mechanical ventilation or length
of hospitalization [77]. Another meta-analysis of several small randomized trials evaluating
surfactant therapy in mechanically ventilated infants with bronchiolitis concluded that
surfactant therapy may shorten the duration of mechanical ventilation and duration of ICU
stay in children with bronchiolitis [78-81]. However, additional studies are needed before
reliable estimates of the magnitude of the effects can be made.

Monitoring clinical status

Respiratory status Repeated clinical assessment of the respiratory system (eg,


respiratory rate; nasal flaring; retractions; grunting) is necessary to identify
deteriorating respiratory status [82].
Early in the admission, hospitalized infants should have monitoring of heart rate,
respiratory rate and SpO2. In settings with respiratory monitoring capabilities (eg,
ICU), respiratory rate should be monitored continuously; in other settings (eg, general
ward), respiratory rate should be monitored with vital signs. Infants with severe
distress or who have apnea should be monitored in the ICU. An arterial or capillary
blood gas sample to assess PCO2 levels may be indicated in children who require
intensive care and should be repeated as clinically indicated. (See 'HFNC and
CPAP' above.)
A change from continuous to intermittent measurement of SpO2 may be instituted as
the clinical course improves [83]. However, consensus regarding a safe and
acceptable SpO2 threshold for hospital discharge is lacking [1,84-87].
In children who do not improve at the expected rate, chest radiographs may be
helpful in excluding other conditions in the differential diagnosis (eg, foreign body
aspiration, heart failure, vascular ring, tuberculosis, cystic fibrosis) [1].
(See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on
'Differential diagnosis'.)
Fluid status The fluid intake and output of infants and children with bronchiolitis
should be assessed regularly. It is also important to monitor urine output. Plasma
antidiuretic hormone levels rarely may be elevated, leading to fluid retention and
hyponatremia [36-38]. (See 'Fluid management' above.)

Clinical course Although discharge criteria vary from center to center, in multicenter-
studies of children younger than two years hospitalized with bronchiolitis, the median
length of stay was two days [88,89]. Length of stay may be shorter in children with
bronchiolitis due to rhinovirus and longer in children with respiratory syncytial virus-
rhinovirus coinfection [88-90]. The respiratory status typically improves over two to five
days [84,91-95]. However, wheezing persists in some infants for a week or longer. The
course may be prolonged in younger infants and those with comorbid conditions (eg,
bronchopulmonary dysplasia) [8,96].

In a multicenter, multiyear prospective study of 1916 children hospitalized with


bronchiolitis, the time between symptom onset and clinical improvement ranged from 1 to
33 days (median four days) [97]. However, 96 percent of patients continued to improve
once they met certain clinical improvement criteria, including no retractions or mild
retractions; decreasing or stable respiratory rate of <60 breaths/minute for age <6 months,
<55 breaths/minute for age 6 to 11 months, <45 breaths/minute for age 12 months;
ambient air oxygen saturation 90 percent and not lower than 88 percent; and ability to
maintain hydration orally. Risk factors for worsening after initial clinical improvement
included age <2 months, <37 weeks gestational age, and severe retractions, apnea, or
dehydration at presentation [1,5,13-15,19,98].

Discharge criteria Minimal clinical criteria for discharge from the hospital or
emergency department include [5,6,26]:

Respiratory rate <60 breaths per minute for age <6 months, <55 breaths per minute
for age 6 to 11 months, and <45 breaths per minute for age 12 months
Caretaker knows how to clear the infant's airway using bulb suctioning
Patient is stable while breathing ambient air; discharge from the hospital requires
that the patient remain stable for at least 12 hours prior to discharge
Patient has adequate oral intake to prevent dehydration
Resources at home are adequate to support the use of any necessary home
therapies (eg, bronchodilator therapy if the trial was successful and this therapy is to
be continued)
Caretakers are confident they can provide care at home
Education of the family is complete (see 'Anticipatory guidance' above)

In addition, we generally prefer that hospitalized children maintain oxygen saturation 90


percent while breathing ambient air because this is predictive of continued improvement
[97]. However, some observational studies suggest that strict adherence to pulse oximetry
criteria is associated with increased health care utilization [4,10,11].

OUTCOME Bronchiolitis is a self-limited illness and resolves without complications in


most previously healthy infants. However, severely affected infants, especially those born
prematurely and those with underlying cardiopulmonary disease or immunodeficiency, are
at increased risk for complications (eg, apnea, respiratory failure, secondary bacterial
infection). (See "Bronchiolitis in infants and children: Clinical features and diagnosis",
section on 'Complications'.)

The overall mortality rate in children hospitalized with respiratory syncytial virus (RSV)
bronchiolitis in developed countries is less than 0.1 percent [99]. Mortality is increased in
young infants (6 to 12 weeks), those with low birth weight, and those with underlying
medical conditions (eg, underlying cardiopulmonary disease, immune deficiency)
[84,100,101].

Infants hospitalized for lower respiratory tract infection (LRTI), especially RSV and
rhinovirus, are at increased risk for recurrent wheezing and reduced pulmonary function,
particularly during the first decade of life [102-107]. In a prospective cohort, LRTI with RSV
increased the risk for subsequent frequent and infrequent wheezing (odds ratio 4.3 and
3.2, respectively) and was associated with reduced forced expiratory volume in children up
to 11 years of age [108]. However, this association was lost by age 13 years, perhaps due
to inadequate sample size. Similar findings have been observed for infants infected with
rhinovirus [106,109].

Whether bronchiolitis in early childhood, especially that caused by RSV and rhinovirus, is
associated with the development of asthma is uncertain. In some studies, a correlation
exists between infection with RSV and the later development of reversible airways
disease. However, this may reflect the multifactorial nature of risk for asthma, including a
genetic predisposition to airway reactivity, exposure to environmental pollutants such as
smoke, immunologic mechanisms, and disruption of the growth and development of the
lungs due to viral infection in early childhood. (See "Risk factors for asthma", section on
'Respiratory infections' and "Respiratory syncytial virus infection: Clinical features and
diagnosis", section on 'Airway reactivity'.)

PREVENTION

Primary and secondary prevention Standard strategies to reduce the risk of


bronchiolitis and accompanying morbidity include hand hygiene (washing with soap or
with alcohol-based rubs) to minimize transmission of infectious agents, minimizing
passive exposure to cigarette smoke, and avoiding contact with individuals with
respiratory tract infections [1].
Immunoprophylaxis with palivizumab, a humanized monoclonal antibody against the
respiratory syncytial virus (RSV) F glycoprotein, decreases the risk of hospitalization
due to severe RSV illness among preterm infants and those with chronic lung disease
and hemodynamically significant congenital heart disease. The American Academy of
Pediatrics guidance for palivizumab immunoprophylaxis has become increasingly
restricted, driven in part by the high cost associated with monthly administration. The
indications and administration of palivizumab are discussed separately.
(See "Respiratory syncytial virus infection: Prevention", section on 'Palivizumab'.)
Vaccines to prevent the most common causes of bronchiolitis (RSV, rhinovirus,
human metapneumovirus, and parainfluenza virus) are unavailable. However, annual
influenza immunization is recommended for everyone older than six months. Priority
is given to children age 6 through 59 months and household contacts of children age
0 through 59 months because children younger than five years are at increased risk
for influenza-related hospitalization and health care utilization. (See "Seasonal
influenza in children: Prevention with vaccines", section on 'Target groups'.)
Prevention of sequelae We do not suggest inhaled glucocorticoids for the
prevention of subsequent wheezing episodes in infants and children with bronchiolitis.
In randomized trials and meta-analysis, inhaled glucocorticoids
(budesonide, fluticasone, dexamethasone) have not been beneficial in reducing
subsequent wheezing episodes [20-23].
We do not suggest montelukast or other leukotriene inhibitors for the prevention of
airway reactivity after bronchiolitis. Randomized trials of montelukast for the
prevention of airway reactivity have had inconsistent results [110-112]; heterogeneity
in severity of disease, duration of treatment, and outcome measures precluded
pooled analysis [25]. However, in the largest trial (n = 979), montelukast was not
associated with improvement in post-RSV bronchiolitis respiratory symptoms [111].

INTERVENTIONS THAT ARE NOT ROUTINELY RECOMMENDED

Bronchodilators

Inhaled bronchodilators We do not suggest routine administration of inhaled


bronchodilators for children with bronchiolitis. Meta-analyses of randomized trials and
systematic reviews suggest that bronchodilators may provide modest short-term
clinical improvement but do not affect overall outcome, may have adverse effects, and
increase the cost of care [13-15,98,113].
Although we do not suggest routine administration of inhaled bronchodilators for
children with first episode of bronchiolitis, a one-time trial of inhaled bronchodilators
(albuterol [salbutamol] or epinephrine) may be warranted for infants and children with
bronchiolitis and severe disease (ie, persistently increased respiratory effort
[tachypnea, nasal flaring, retractions, accessory muscle use, grunting], hypoxemia,
apnea, or respiratory failure).
Children with severe disease or respiratory failure generally were excluded from trials
evaluating inhaled bronchodilators in children with bronchiolitis. In addition, a subset
of young children with the clinical syndrome of bronchiolitis may have virus-induced
wheezing or asthma and may benefit from inhaled bronchodilator therapy. In a
prospective multicenter study of children hospitalized with bronchiolitis, children with
rhinovirus-associated bronchiolitis were more likely than those with respiratory
syncytial virus-associated bronchiolitis to be >12 months of age and to have a history
of wheezing and eczema [114], groups that also may have been excluded from trials
evaluating bronchodilators. (See 'Emergency department management' above
and 'Other therapies' above and "Treatment of recurrent virus-induced wheezing in
young children", section on 'Inhaled short-acting beta2-agonists'.)
For patients in whom such a trial is warranted, we
suggest albuterol 0.15 mg/kg (minimum 2.5 mg; maximum 5 mg) diluted in 2.5 to 3
mL normal (0.9 percent) saline and administered over 5 to 15 minutes or four to six
puffs via a metered dose inhaler with spacer and face mask. We prefer albuterol
to epinephrine because albuterol is more appropriate for administration in the home
setting. The effects should be monitored by evaluating the child before and up to one
hour after treatment, recognizing that the clinician's ability to assess response may be
limited [115]. If there is a clinical response to albuterol, it can be administered as
needed (based on clinical status) every four to six hours and discontinued when the
signs and symptoms of respiratory distress improve [14].
The clinical practice guidelines of the American Academy of Pediatrics (AAP, 2014)
and the Scottish Intercollegiate Guidelines Network (2006), the "Choose Wisely"
workgroup of the Society of Hospital Medicine (2013), and the National Institute of
Health and Care Excellence (NICE, 2015) recommend that bronchodilators not be
used routinely in the management of bronchiolitis [1,5,19,26].
Oral bronchodilators We recommend against the use of oral bronchodilators in
the management of bronchiolitis. In randomized trials, oral bronchodilators have
neither shortened clinical illness nor improved clinical parameters, but were
associated with adverse effects (eg, increased heart rate) [16-18].

Glucocorticoids

Systemic glucocorticoids For healthy infants and young children with


a first episode of bronchiolitis, we recommend not using systemic glucocorticoids
[1,19,24].
Although the anti-inflammatory effects of glucocorticoids theoretically reduce airway
obstruction by decreasing bronchiolar swelling, most studies show little effect in
bronchiolitis. In a 2013 meta-analysis evaluating the use of systemic glucocorticoids
(oral, intramuscular, or intravenous) for acute bronchiolitis in children (0 to 24 months
of age), no significant differences were found in hospital admission rate, length of
stay, clinical score after 12 hours, or hospital readmission rate [23].
Whether glucocorticoids provide benefit in subgroups of children with bronchiolitis is
uncertain. Some patients presenting with the first episode of bronchiolitis may be
experiencing inflammation from asthma, and these patients can benefit from systemic
glucocorticoids. Although patients with asthma can benefit from glucocorticoids,
randomized controlled trials have demonstrated no benefit of oral glucocorticoids in
young children with virus-associated wheezing [27,116]. (See "Acute asthma
exacerbations in children: Emergency department management" and "Acute asthma
exacerbations in children: Inpatient management" and "Treatment of recurrent virus-
induced wheezing in young children", section on 'Systemic glucocorticoids'.)
Inhaled glucocorticoids We do not suggest inhaled glucocorticoids for the
treatment of bronchiolitis. In randomized trials and meta-analysis, inhaled
glucocorticoids (budesonide, fluticasone, dexamethasone) have not been beneficial in
reducing symptom duration or readmission rates [20-23].
Bronchodilators plus glucocorticoids We do not suggest combination therapy
with bronchodilators plus glucocorticoids for infants and children with a first episode of
bronchiolitis. Although a randomized trial suggested that administration of
nebulized epinephrine and oral dexamethasone in the emergency department
decreased the rate of hospitalization within one week of the emergency department
visit, the result was not significant when adjusted for multiple comparisons [27].
Additional support of benefit and additional information about the long-term effects of
combination bronchodilator/glucocorticoid therapy is necessary before combination
therapy can be considered for infants with a first episode of virus-induced wheezing
[27,117].
Nebulized hypertonic saline For infants and children with severe bronchiolitis who are
treated in the emergency department, we suggest not routinely treating with nebulized
hypertonic saline (of any concentration). In 2015 systematic reviews of randomized trials
evaluating administration of hypertonic saline in the emergency department, hypertonic
saline reduced the rate of hospitalization among children with bronchiolitis, but the
evidence was not high quality [26,118].

For infants and children admitted to the hospital with bronchiolitis, we suggest not routinely
treating with nebulized hypertonic saline. Although two meta-analyses found low-quality
evidence that nebulized hypertonic saline reduces length of stay (by approximately one-
half day) [118,119], a subsequent meta-analysis found no effect when the data were
reanalyzed to control for heterogeneity (eg, imbalance between mean day of illness at
presentation between treatment groups, divergent outcome definition) [120].

Most of the trials included in the systematic reviews administered hypertonic saline with
bronchodilators. A subsequent randomized, comparator-controlled trial found that,
compared with normal saline, 3 percent hypertonic saline administered every four hours
without bronchodilators did not reduce length of stay in infants younger than 12 months of
age who were hospitalized with bronchiolitis and had no significant comorbidities [121].
Well-designed randomized, comparator-controlled studies suggest no benefit from
hypertonic saline for the treatment of infants hospitalized with bronchiolitis [121-124]. Until
additional high quality studies show otherwise, nebulized hypertonic saline cannot be
routinely recommended for hospitalized children with bronchiolitis [125].

The 2015 NICE bronchiolitis guideline recommends against the use of hypertonic saline in
children with bronchiolitis [26]. The 2014 AAP clinical practice guideline on the
management of bronchiolitis indicated that clinicians "may administer hypertonic saline to
infants and children hospitalized for bronchiolitis" [1].

Chest physiotherapy We suggest that chest physiotherapy not be used routinely in the
management of bronchiolitis. A systematic review of 12 randomized trials concluded that
chest physiotherapy did not reduce severity of disease or time to recovery [126]. The use
of chest physiotherapy is discouraged because it may increase the distress and irritability
of ill infants.

Chest physiotherapy may be warranted in children with comorbidities associated with


difficulty clearing respiratory secretions (eg, neuromuscular disorders, cystic fibrosis) [26].

Antimicrobial agents and immunotherapies

Antibiotics Antibiotics should not be used routinely in the treatment of


bronchiolitis, which is almost always caused by viruses [127-129]. Bronchiolitis does
not increase the risk for serious bacterial infection. However, occasionally
concomitant or secondary bacterial infections may occur. Coexisting bacterial
infections should be treated in the same manner as they would be treated in the
absence of bronchiolitis. (See "Bronchiolitis in infants and children: Clinical features
and diagnosis", section on 'Microbiology' and "Febrile infant (younger than 90 days of
age): Outpatient evaluation", section on 'Bronchiolitis'.)
Ribavirin We do not recommend ribavirin in the routine treatment of infants and
children with bronchiolitis. However, in immunocompromised patients with severe
bronchiolitis due to respiratory syncytial virus (RSV), antiviral therapy may play a role.
(See "Respiratory syncytial virus infection: Treatment", section on 'Ribavirin'.)
Anti-RSV preparations We do not recommend anti-RSV preparations for the
treatment of bronchiolitis in infants and children. In randomized trials,
intravenous immune globulin with a high neutralizing activity against RSV (RSV-IGIV,
which has been discontinued) and RSV-specific humanized monoclonal antibody
(palivizumab) failed to improve outcomes in infants (with or without risk factors)
hospitalized with RSV infection [130,131]. (See "Respiratory syncytial virus infection:
Prevention", section on 'Palivizumab'.)

Heliox We do not suggest the routine use of heliox (a 70/30 or 80/20 mixture of helium
and oxygen, respectively) in the treatment of bronchiolitis in infants and children. The
administration of heliox is cumbersome and results in a relatively small benefit in a limited
group of infants. A 2015 systematic review of seven heterogeneous randomized trials of
heliox for the treatment of moderate or severe bronchiolitis concluded that heliox did not
reduce the rate of intubation, rate of discharge from the emergency department, or the
length of treatment for respiratory distress [132]. (See "Physiology and clinical use of
heliox", section on 'Technical issues'.)

Leukotriene inhibitors We do not suggest montelukast or other leukotriene inhibitors


for the treatment of bronchiolitis. Although leukotrienes appear to play a role in airway
inflammation in bronchiolitis [133-136], a 2015 meta-analysis of five randomized trials
found no effect on duration of hospitalization or clinical scores in children with bronchiolitis
[25]. Additional studies are necessary to determine what role, if any, leukotriene inhibitors
play in the management of acute bronchiolitis [137,138].

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or email these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient education: Bronchiolitis (and RSV) (The Basics)")
Beyond the Basics topics (see "Patient education: Bronchiolitis (and RSV) in infants
and children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Bronchiolitis is broadly defined as a clinical syndrome that occurs in children <2


years of age and is characterized by upper respiratory symptoms leading to lower
respiratory infection with inflammation, which results wheezing and or crackles. It
typically occurs with primary infection or reinfection with a viral pathogen.
(See 'Definition' above and "Bronchiolitis in infants and children: Clinical features and
diagnosis", section on 'Diagnosis'.)
Infants and children with moderate to severe respiratory distress (eg, nasal flaring;
retractions; grunting; respiratory rate >70 breaths per minute; dyspnea; cyanosis)
usually require hospitalization for supportive care and monitoring. Additional
indications for hospitalization include toxic appearance, poor feeding, lethargy,
apnea, and/or hypoxemia. (See 'Indications for hospitalization' above.)
Infants and children with nonsevere bronchiolitis usually can be managed in the
outpatient setting, unless there are concerns about the caregivers' ability to care for
them at home. Supportive care (maintenance of adequate hydration, relief of
nasal congestion/obstruction, monitoring disease progression) and anticipatory
guidance are the mainstays of management. We generally do not use pharmacologic
interventions (eg, bronchodilators, glucocorticoids) or nebulized hypertonic saline in
the management of children with nonsevere bronchiolitis. (See 'Severity
assessment' above and 'Nonsevere bronchiolitis' above.)
Infants and children with severe bronchiolitis usually require treatment in the
emergency department or inpatient setting. Supportive care (maintenance of
adequate hydration, provision of oxygen and respiratory support as necessary,
monitoring disease progression) and anticipatory guidance are the mainstays of
management of severe bronchiolitis. (See 'Severity assessment' above and 'Severe
bronchiolitis' above and 'Fluid management' above and 'Supplemental oxygen' above
and 'Monitoring clinical status' above.)
We suggest not routinely administering inhaled bronchodilators
(albuterol or epinephrine) to infants and children with a first episode of
bronchiolitis (Grade 2B). (See 'Bronchodilators' above.)
However, a one-time trial of inhaled bronchodilators may be warranted for infants
and children with bronchiolitis and severe disease. The bronchodilator response
should be objectively assessed before and up to one hour after treatment. If
there is a clinical response, aerosolized bronchodilator therapy can be
administered every four to six hours as needed (based on clinical status) and
discontinued when the signs and symptoms of respiratory distress improve.
(See 'Severity assessment' above and 'Severe bronchiolitis' above
and 'Bronchodilators' above.)
We recommend not using systemic glucocorticoids routinely in the treatment of
previously healthy infants hospitalized with a first episode of bronchiolitis (Grade
1A). We also suggest not using combination therapy with bronchodilators and
glucocorticoids for infants and children with bronchiolitis (Grade 2B).
(See 'Glucocorticoids' above.)
We suggest not using nebulized hypertonic saline or heliox routinely in the
treatment of bronchiolitis in infants and children (Grade 2B). (See 'Nebulized
hypertonic saline' above and 'Heliox' above.)
Infants and children with bronchiolitis and arterial or capillary carbon dioxide tension
>55 mmHg, hypoxemia despite oxygen supplementation, and/or apnea may require
mechanical ventilation. Noninvasive strategies that may be effective in reducing work
of breathing, improving gas exchange, and avoiding the need for endotracheal
intubation include heated humidified high-flow nasal cannula therapy and continuous
positive pressure ventilation. (See 'HFNC and CPAP' above.)
Minimal clinical criteria for discharge from the hospital, emergency department, or
office include respiratory rate of <60 breaths per minute for age <6 months, <55
breaths per minute for age 6 to 11 months, and <45 breaths per minute for age 12
months; clinical stability without requiring supplemental oxygen; oral intake sufficient
to prevent dehydration; and education of the family. (See 'Discharge criteria' above
and 'Anticipatory guidance' above.)
General strategies to prevent bronchiolitis include hand hygiene, minimizing passive
exposure to cigarette smoke, avoiding contact with individuals with respiratory tract
infections, and annual influenza immunization (for individuals older than six months).
Immunoprophylaxis with palivizumab may decrease the risk of hospitalization in
infants with bronchopulmonary dysplasia, premature infants, and hemodynamically
significant congenital heart disease. (See 'Prevention' above and "Respiratory
syncytial virus infection: Prevention" and "Respiratory syncytial virus infection:
Prevention", section on 'Indications for palivizumab'.)

Bronchiolitis in infants and children: Clinical features and diagnosis

Authors:
Pedro A Piedra, MD
Ann R Stark, MD
Section Editors:
Gregory Redding, MD
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Nov 03, 2016.

INTRODUCTION Bronchiolitis, a lower respiratory tract infection that primarily affects


the small airways (bronchioles), is a common cause of illness and hospitalization in infants
and young children.

The microbiology, epidemiology, clinical features, and diagnosis of bronchiolitis will be


presented here. The treatment, outcome, and prevention of bronchiolitis in children;
respiratory syncytial virus; and the emergent evaluation of children with acute respiratory
distress are discussed separately:

(See "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)


(See "Respiratory syncytial virus infection: Clinical features and
diagnosis" and "Respiratory syncytial virus infection: Treatment" and "Respiratory
syncytial virus infection: Prevention".)
(See "Acute respiratory distress in children: Emergency evaluation and initial
stabilization".)

DEFINITION Bronchiolitis is broadly defined as a clinical syndrome that occurs in


children <2 years of age and is characterized by upper respiratory symptoms (eg,
rhinorrhea) followed by lower respiratory infection with inflammation, which results in
wheezing and/or crackles (rales). Bronchiolitis typically occurs with primary infection or
reinfection with a viral pathogen [1-3]. In young children, the clinical diagnosis of
bronchiolitis may overlap with recurrent virus-induced wheezing and acute viral-triggered
asthma. (See "Virus-induced wheezing and asthma: An overview".)

For clinical research, bronchiolitis is typically defined as the first episode of wheezing in a
child younger than 12 to 24 months who has physical findings of a viral lower respiratory
infection and no other explanation for the wheezing [4,5].

PATHOGENESIS Bronchiolitis occurs when viruses infect the terminal bronchiolar


epithelial cells, causing direct damage and inflammation in the small bronchi and
bronchioles. Edema, excessive mucus, and sloughed epithelial cells lead to obstruction of
small airways and atelectasis. Based upon biopsy or autopsy samples in severe cases and
animal studies, pathologic changes begin 18 to 24 hours after infection and include
bronchiolar cell necrosis, ciliary disruption, and peribronchiolar lymphocytic infiltration [6-
8].

MICROBIOLOGY Bronchiolitis typically is caused by a viral infection. Although the


proportion of disease caused by specific viruses varies depending upon the season and
the year, respiratory syncytial virus (RSV) is the most common cause, followed by
rhinovirus [9-13]. Less common causes include parainfluenza virus, human
metapneumovirus, influenza virus, adenovirus, coronavirus, and human bocavirus
[10,11,14,15]. With molecular diagnostics, a viral etiology can be identified in >95 percent
of cases; two or more viruses are detected in approximately one-third of young children
hospitalized with bronchiolitis [9,16-18]. In addition, lower respiratory tract infection and
wheezing episodes in infants infrequently are associated with Mycoplasma
pneumoniae and Bordetella pertussis. (See "Mycoplasma pneumoniae infection in
children", section on 'Clinical features' and "Pertussis infection in infants and children:
Clinical features and diagnosis", section on 'Clinical features'.)

RSV RSV is the most common cause of bronchiolitis and the virus most often
detected as the sole pathogen. RSV is ubiquitous throughout the world and causes
seasonal outbreaks. In temperate climates, late fall and winter epidemics of
bronchiolitis usually are linked to RSV. In tropical and semitropical climates, the
seasonal outbreaks usually are associated with the rainy season. (See "Respiratory
syncytial virus infection: Clinical features and diagnosis".)
Rhinovirus Human rhinoviruses are the main cause of the common cold. There
are more than 170 serotypes. Rhinovirus is associated with lower respiratory tract
infection in young children and in individuals with chronic pulmonary disease [19].
Dual viral infections are often detected. Rhinovirus is often associated with
bronchiolitis in the spring and fall [20]. (See "Epidemiology, clinical manifestations,
and pathogenesis of rhinovirus infections".)
Parainfluenza virus Parainfluenza virus type 3, which is associated with epidemics
in early spring and fall, is another cause of bronchiolitis. Parainfluenza virus types 1
and 2 also can cause bronchiolitis although croup is the more common presentation
[21]. (See "Parainfluenza viruses in children", section on 'Clinical presentation'.)
Human metapneumovirus Human metapneumovirus sometimes occurs in
conjunction with other viral infections and has been identified as an etiology of
bronchiolitis and pneumonia in children [22,23]. (See "Human metapneumovirus
infections".)
Influenza virus The lower respiratory tract manifestations of influenza are clinically
indistinguishable from those due to RSV or parainfluenza viral infections.
(See "Seasonal influenza in children: Clinical features and diagnosis", section on
'Clinical features'.)
Adenovirus Adenovirus may cause lower respiratory tract infections, including
bronchiolitis, bronchiolitis obliterans, and pneumonia, though it more typically causes
pharyngitis and coryza. Adenovirus can also infect other organs causing disseminated
disease. (See "Epidemiology and clinical manifestations of adenovirus infection",
section on 'Clinical presentation'.)
Coronavirus Human coronaviruses are another important cause of the common
cold, which can also cause lower respiratory tract infection, including bronchiolitis
[24,25]. Severe acute respiratory syndrome (SARS) was caused by a coronavirus that
likely originated from the Chinese horseshoe bat [26]. Middle East respiratory
syndrome (MERS) is also caused by a coronavirus that was first detected in the
Arabian Peninsula in 2012. (See "Coronaviruses".)
Human bocavirus Human bocavirus 1 causes upper and lower respiratory
infections during the fall and winter months [14,27-29]. Bronchiolitis and pertussis-like
illness can occur. Human bocavirus 2 through 4 are primarily enteric viruses [30].

EPIDEMIOLOGY Bronchiolitis typically affects infants and children younger than two
years, principally during the fall and winter [31,32]. Bronchiolitis hospitalization has a peak
incidence between two and six months of age and remains a significant cause of
respiratory disease during the first two years of life [33]. It is a leading cause of
hospitalization in infants and young children [32-34].

The epidemiology of bronchiolitis is similar to that of respiratory syncytial virus (RSV)


infection because most cases of bronchiolitis are caused by RSV. (See "Respiratory
syncytial virus infection: Clinical features and diagnosis", section on 'Epidemiology'.)

RISK FACTORS FOR SEVERE DISEASE Risk factors for severe or complicated
bronchiolitis include [35-41]:

Prematurity (gestational age 36 weeks)


Low birth weight
Age less than 12 weeks
Chronic pulmonary disease, particularly bronchopulmonary dysplasia (also known
as chronic lung disease)
Anatomic defects of the airways
Hemodynamically significant congenital heart disease
Immunodeficiency
Neurologic disease

Environmental and other risk factors, such as passive smoking, crowded household,
daycare attendance, being born approximately two months before or after the start of the
epidemic, concurrent birth siblings, older siblings, and high altitude (>2500 meters) can
also contribute to more severe disease [40,42-45].

CLINICAL FEATURES

Clinical presentation Bronchiolitis is a clinical syndrome that occurs primarily in


children younger than two years of age and generally presents with fever (usually 38.3C
[101F]), cough, and respiratory distress (eg, increased respiratory rate, retractions,
wheezing, crackles). It often is preceded by a one- to three-day history of upper respiratory
tract symptoms (eg, nasal congestion and/or discharge) [46]. Respiratory distress,
increased work of breathing, respiratory rate, and oxygenation all can change rapidly with
crying, coughing, and agitation. Oxyhemoglobin desaturation can occur under all of these
circumstances as well as during sleep when chest wall muscles relax, further narrowing
intrathoracic airways.

Clinical course The duration of the illness due to bronchiolitis depends upon age,
severity of illness, associated high-risk conditions (eg, prematurity, chronic pulmonary
disease), and the causative agent [9]. Bronchiolitis usually is a self-limited disease. Most
children who do not require hospitalization recover by 28 days [47-49].

Typical illness with bronchiolitis begins with upper respiratory tract symptoms, followed by
lower respiratory tract signs and symptoms on days two to three, which peak on days
three to five and then gradually resolve. In a systematic review of four studies including
590 children with bronchiolitis who were seen in outpatient settings and not treated with
bronchodilators [5,48-50], the mean time to resolution of cough ranged from 8 to 15 days
[51]. Cough resolved in 50 percent of patients within 13 days and in 90 percent within 21
days. In a cohort of 181 children (not included in the systematic review), the median
duration of caretaker-reported symptoms was 12 days; approximately 20 percent
continued to have symptoms for at least three weeks, and 10 percent had symptoms for at
least four weeks [47].

Although discharge criteria vary from center to center, in multicenter studies of children
younger than two years hospitalized with bronchiolitis, the median length of stay was two
days [9,52]. Length of stay may be shorter in children with bronchiolitis due to rhinovirus
and longer in children with bronchiolitis due to respiratory syncytial virus (RSV)-rhinovirus
co-infection. The respiratory status typically improves over two to five days [36,53-56].
However, wheezing persists in some infants for a week or longer.

The course may be prolonged in infants younger than six months (particularly those
younger than 12 weeks) and those with comorbid conditions (eg, bronchopulmonary
dysplasia); these children often are severely affected and may require assisted ventilation
[35,57]. (See 'Risk factors for severe disease' above and 'Respiratory failure' below.)

Complications In most previously healthy infants, bronchiolitis resolves without


complications. However, severely affected patients, particularly those born prematurely,
<12 weeks of age, or who have underlying cardiopulmonary disease or immunodeficiency,
are at increased risk for complications, the most serious of which are apnea and
respiratory failure [58]. Infants who require mechanical ventilation for apnea or respiratory
failure may develop air leak, such as pneumothorax or pneumomediastinum.

Dehydration Infants with bronchiolitis may have difficulty maintaining adequate


hydration because of increased fluid needs (related to fever and tachypnea), decreased
oral intake (related to tachypnea and respiratory distress), and/or vomiting [59]. They
should be monitored for dehydration (eg, increased heart rate, dry mucosa, sunken
fontanelle, decreased urine output (table 1)). Parenteral or nasogastric fluid administration
may be necessary. (See "Clinical assessment and diagnosis of hypovolemia (dehydration)
in children", section on 'Clinical assessment' and "Bronchiolitis in infants and children:
Treatment, outcome, and prevention", section on 'Fluid management'.)

Aspiration pneumonia Bronchiolitis may be complicated by aspiration pneumonia. The


risk of aspiration increases during active bronchiolitis and resolves weeks later as
tachypnea and the work of breathing subside.

Apnea Bronchiolitis may be complicated by apnea, particularly in infants born


prematurely and those younger than two months (ie, those with postmenstrual age <48
weeks) [58,60-66]. The risk of apnea is not specific to a particular pathogen [64].
Presenting with apnea is a risk factor for respiratory failure and the need for mechanical
ventilation. (See 'Respiratory failure' below.)

In a three-year multicenter prospective study (2007 to 2010) that included 2156 children <2
years hospitalized with bronchiolitis, apnea was documented in 5 percent [64]. The study
focused on sicker patients by aiming to enroll 20 percent of patients from the intensive
care unit. Independent risk factors for apnea included age <8 weeks (age was corrected
for gestational age if born preterm), caretaker report of previous apnea during the illness,
high or low respiratory rate at presentation (ie, respiratory rate <30 or
>70 breaths/minute), and room air oxygen saturation <90 percent at presentation. Similar
risk factors for apnea were identified in large prospective and retrospective cohorts [63,66].
The risk of apnea was not increased with RSV compared with other viral pathogens [64].

These findings suggest that low respiratory (ie, <30 breaths/minute) rate in children with
bronchiolitis is not necessarily reassuring and that results of virologic studies are not
helpful in determining the risk for apnea among hospitalized infants.

Respiratory failure Respiratory failure is another serious complication of bronchiolitis.


In a multicenter study, 14 percent of 684 infants younger than 12 months who were
hospitalized for management of bronchiolitis required mechanical ventilation for respiratory
failure or apnea [58]. In another multicenter study, 16 percent of infants and children
younger than two years hospitalized with RSV required intensive care support (with or
without mechanical ventilation) [36]. However, the need for intensive care varied
depending on the presence and type of risk factors for serious disease:

No known risk factors 7 percent


Congenital heart disease, bronchopulmonary dysplasia, or immunosuppression 19
to 37 percent
Age <6 weeks 29 percent

Hypoxemia, associated with mucus plugging and atelectasis, is common in children with
bronchiolitis. It may respond to supplemental oxygen alone, although sometimes it
requires additional respiratory support. Hypercapnic respiratory failure, associated with
fatigue, usually requires additional respiratory support (eg, intubation and mechanical
ventilation).

Between 2000 and 2009, approximately 2 percent of children younger than two years
hospitalized with bronchiolitis in the Kids Inpatient Database required mechanical
ventilation [32]. Requirement for mechanical ventilation was increased in infants younger
than 12 months and high-risk medical conditions.

Secondary bacterial infection With the exception of otitis media, secondary bacterial
infection is uncommon among infants and young children with bronchiolitis or RSV
infection. In a nine-year prospective study of 565 children (<3 years) hospitalized with
documented RSV infection, subsequent bacterial infection developed in only 1.2 percent
and subsequent bacterial pneumonia in 0.9 percent [67]. The risk of secondary bacterial
pneumonia is increased among children who require admission to the intensive care unit,
particularly those who require intubation [68,69].

RADIOGRAPHIC FEATURES Chest radiographs are not necessary in the routine


evaluation of bronchiolitis [2,3]. They should be obtained only if there are clinical findings
suggestive of other potential diagnoses [1,70]. (See 'Differential diagnosis' below.)

Radiographic features of bronchiolitis, which are variable and nonspecific, include


hyperinflation and peribronchial thickening (image 1) [71,72]. Patchy atelectasis with
volume loss may result from airway narrowing and mucus plugging. Segmental
consolidation and alveolar infiltrates are more characteristic of bacterial pneumonia than
bronchiolitis, but radiographic findings are poor indicators of the etiologic diagnosis and
must be used in conjunction with other clinical features in making decisions about
diagnosis and treatment. (See 'Differential diagnosis' below and "Community-acquired
pneumonia in children: Clinical features and diagnosis", section on 'Etiologic clues'.)

In infants and young children with mild disease, radiographs are unlikely to alter treatment
and may lead to inappropriate use of antibiotics [2,71,73]. However, in infants and young
children with moderate or severe respiratory distress (eg, nasal flaring, retractions,
grunting, respiratory rate >70 breaths/minute, dyspnea, or cyanosis), radiographs may be
warranted, particularly if there are focal findings on examination, the infant has a cardiac
murmur, or it is necessary to exclude alternate diagnoses [2]. Radiographs also may be
indicated to exclude alternate diagnoses in children who fail to improve at the expected
rate [3]. (See 'Severity assessment' below and 'Differential diagnosis' below and 'Clinical
course' above.)

EVALUATION The evaluation of infants and young children with suspected bronchiolitis
generally requires only history and physical examination, including pulse oximetry.
Laboratory studies and radiographs usually are not necessary for diagnosis but may be
warranted to evaluate complications, comorbid infections, or other conditions in the
differential diagnosis. The evaluation outlined below is largely consistent with that
suggested in the American Academy of Pediatrics 2014 clinical practice guideline for the
diagnosis, management, and prevention of bronchiolitis [3].

History Infants with moderate to severe bronchiolitis typically present for medical
attention three to six days after illness onset. Bronchiolitis often is preceded by a one- to
three-day history of upper respiratory tract symptoms, such as nasal
congestion and/or discharge and mild cough [46]. It typically presents with fever (usually
38.3C [101F), cough, and respiratory distress (eg, increased respiratory rate,
retractions).

Compared with other viruses that cause bronchiolitis, fever tends to be lower with
respiratory syncytial virus (RSV) and higher with adenovirus [74]. (See "Respiratory
syncytial virus infection: Clinical features and diagnosis", section on 'Clinical
manifestations' and "Epidemiology and clinical manifestations of adenovirus infection",
section on 'Clinical presentation'.)

Aspects of the history of present illness that help in determining the severity of
illness and/or need for hospitalization include (see 'Severity assessment' below
and "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on
'Indications for hospitalization') [3,75]:

Assessment of hydration status (eg, fluid intake, urine output)


Symptoms of respiratory distress (tachypnea, nasal flaring, retractions, grunting)
Cyanosis
Episodes of restlessness or lethargy (may indicate hypoxemia and/or impending
respiratory failure)
A history of apnea with or without cyanosis or bradycardia

Aspects of the past medical history associated with severe disease include prematurity,
chronic pulmonary disease, anatomic abnormalities of the airways, hemodynamically
significant congenital heart disease, immunodeficiency, and neurologic disease. (See 'Risk
factors for severe disease' above.)

Examination Characteristic examination findings of bronchiolitis include tachypnea,


intercostal and subcostal retractions, expiratory wheezing, and cough. Additional
auscultatory findings may include prolonged expiratory phase and coarse or fine crackles
(rales). The chest may appear hyperexpanded with increased anteroposterior diameter
and may be hyperresonant to percussion. Hypoxemia (oxygen saturation <95 percent)
commonly is detected by pulse oximetry. Other findings may include conjunctivitis,
pharyngitis, and acute otitis media [76-78].

Severely affected patients have increased work of breathing (subcostal, intercostal, and
supraclavicular retractions; nasal flaring; and expiratory grunting). They may appear
cyanotic and have poor peripheral perfusion. Wheezing may not be audible if the airways
are profoundly narrowed or when increased work of breathing results in exhaustion.

Labs and imaging for select patients Laboratory tests are not routinely indicated in
the evaluation of infants and young children with bronchiolitis. However,
laboratory and/or radiographic evaluation may be necessary to evaluate the possibility of:

Comorbid or secondary bacterial infection in:


Neonates 28 days of age with fever Infants 28 days old with fever (T
38C [100.4F]) and symptoms and signs of bronchiolitis have the same risk for
serious bacterial infection as young febrile infants without bronchiolitis and
should be assessed accordingly [79]. (See "Febrile infant (younger than 90 days
of age): Outpatient evaluation".)
Infants 28 to 90 days of age with fever Complete blood count (CBC),
urinalysis, urine culture, and chest radiograph may be warranted to exclude
comorbid or secondary bacterial infection in febrile (T 38C [100.4F]) infants
with symptoms and signs of bronchiolitis who are between 28 and 90 days of
age. However, the yield of this evaluation is likely to be low. Although the CBC is
often used to screen for serious bacterial infection in infants without bronchiolitis,
in systematic reviews and a large retrospective study, abnormal white blood cell
count was not predictive of serious bacterial infection in infants and young
children who were hospitalized with RSV [1,80,81]. (See "Febrile infant (younger
than 90 days of age): Management", section on 'Management'.)
Serious comorbid infection is uncommon in children with bronchiolitis. In
prospective studies, the risk for bacteremia or meningitis among febrile infants
and young children with bronchiolitis is typically less than 1 to 2 percent [79,82-
84]. The risk for urinary tract infection (UTI), which ranges from 1 to 5 percent, is
less than that for febrile infants without bronchiolitis (approximately 10 to 20
percent, depending on age, sex, circumcision status, etc), though it is not
negligible. (See "Febrile infant (younger than 90 days of age): Outpatient
evaluation", section on 'Bronchiolitis'.)
Complications or other diagnostic considerations in:
Children of any age with unusual or severe course CBC and chest
radiograph may be warranted to evaluate secondary bacterial infection and other
conditions in the differential diagnosis in infants and young children with an
unusual or prolonged or severe course (eg, failure to improve after two to five
days, wheezing that persists for more than one week) [1]. (See 'Clinical
course' above and 'Differential diagnosis' below.)
Children of any age with severe disease In infants and young children with
severe disease, arterial or capillary blood gas measurements may be necessary
to evaluate respiratory failure. (See 'Respiratory failure' above.)

DIAGNOSIS
Clinical diagnosis Bronchiolitis is diagnosed clinically. Characteristic features include a
viral upper respiratory prodrome followed by increased respiratory effort (eg, tachypnea,
nasal flaring, chest retractions) and wheezing and/or rales in children younger than two
years of age [1-3]. (See 'History' above and 'Examination' above.)

Chest radiographs and laboratory studies are not necessary to make the diagnosis of
bronchiolitis and should not be routinely performed [3]. However, they may be necessary
to evaluate the possibility of secondary or comorbid bacterial infection, complications, or
other conditions in the differential diagnosis, particularly in children who have pre-existing
cardiopulmonary disease [1,3,80]. (See 'Complications' above and 'Differential
diagnosis' below and 'Labs and imaging for select patients' above.)

Virology We do not routinely suggest testing for specific viral agents in children with
bronchiolitis unless the results of such testing will alter management of the patient or
patient's contacts (eg, discontinuation of palivizumab prophylaxis, initiation
or continuation/discontinuation of antibiotic therapy, anti-influenza therapy, or isolation or
cohorting of hospitalized patients or caregivers) [1,85]. (See "Seasonal influenza in
children: Prevention and treatment with antiviral drugs", section on 'Antiviral therapy'.)

There is debate about whether testing for specific viral agents alters clinical management
or outcome, particularly in the outpatient setting [1,80,85-89]. However, the identification of
a viral etiologic agent during emergency department evaluation or in hospitalized patients
has been associated with a decreased utilization of antibiotic treatment in some studies
[87,90-94].

Identification of the responsible virus in hospitalized patients may help to avoid health
care-associated transmission by permitting cohorting of patients and/or caregivers.
However, direct evidence that this strategy prevents transmission of respiratory viruses in
children is lacking, and it may be more logical to isolate all infants with bronchiolitis [1,95].
Cohorting has the potential to increase the risk of infection with other respiratory viruses
leading to prolonged hospitalization [9]. (See "Respiratory syncytial virus infection:
Prevention", section on 'Health care-associated infection'.)

Approach to testing When an etiologic diagnosis is necessary (eg, for isolating or


cohorting hospitalized patients or caregivers, if the results will affect other management
decisions such as whether to initiate or continue antibiotic therapy), it can be confirmed
with molecular assays (eg, single or multiplex polymerase chain reaction [PCR]), antigen
detection, immunofluorescence, or culture.

For hospitalized patients, molecular assays are preferred to antigen detection or


immunofluorescence given the increased sensitivity and ability to assess a broader
panel of respiratory viruses.
Rapid antigen tests are available for respiratory syncytial virus (RSV), parainfluenza,
adenovirus, and influenza viruses. The sensitivity of most rapid antigen tests ranges
from 80 to 90 percent [96].
Direct or indirect immunofluorescence tests also are available for RSV,
parainfluenza, adenovirus, influenza virus, and other viruses that cause bronchiolitis.
Culture is another method that can be used for viral identification, but results may
not be available in time for clinical decision-making.

The laboratory diagnosis depends upon the quality and proper handling of the specimen.
Virologic testing should be performed on respiratory specimens obtained by nasal wash or
nasal aspirate; midturbinate nasal swab is also acceptable [97,98].

Nasal wash specimens are obtained by holding the infant or child upright at a 45 angle. A
bulb syringe or a soft plastic catheter attached to suction is used to aspirate nasal
secretions after a small amount of normal saline (1 to 3 mL) is instilled in each nostril.

Severity assessment Severe bronchiolitis is indicated by persistently increased


respiratory effort (tachypnea; nasal flaring; intercostal, subcostal, or suprasternal
retractions; accessory muscle use; grunting), hypoxemia, apnea, or acute respiratory
failure [99]. Repeated observations are necessary to adequately assess disease severity
because examination findings may vary substantially over time [3]. Infants and young
children with severe disease usually require hospitalization for frequent observation as well
as respiratory and/or fluid support. (See "Bronchiolitis in infants and children: Treatment,
outcome, and prevention", section on 'Indications for hospitalization'.)

Other factors that have been associated with increased illness severity include toxic or ill
appearance, oxygen saturation <90 percent by pulse oximetry while breathing room air,
respiratory rate 70 breaths/minute, and atelectasis on chest radiograph [35,36,100].
However, there is limited and/or conflicting evidence relating these clinical findings to
clinical outcomes [3,35,36,53,72,101,102].

Several scoring instruments have been developed to assess the clinical severity of
bronchiolitis in research settings [103-107]. The use of these measures in clinical practice
is limited by lack of sufficient validation [108].

DIFFERENTIAL DIAGNOSIS Bronchiolitis must be distinguished from a variety of acute


and chronic conditions that affect the respiratory tract, including recurrent viral-triggered
wheezing or asthma, pneumonia, chronic pulmonary disease, foreign body aspiration,
aspiration pneumonia, congenital heart disease, heart failure, and vascular ring [78,109].
Severe bronchiolitis also can unmask underlying airway obstruction that existed before the
infection (eg, vascular ring). Clinical features (eg, lack of preceding upper respiratory tract
symptoms, witnessed episode of choking, differential aeration, poor growth) may help to
distinguish some of these conditions from bronchiolitis; for others, radiographic or
laboratory studies may be necessary.
Recurrent viral-triggered wheezing Recurrent viral-
triggered wheezing/recurrent wheezing is a major consideration in the differential
diagnosis of bronchiolitis in older infants and toddlers. A history of recurrent wheezing
episodes and a family or personal history of asthma, eczema, and atopy help to
support a diagnosis of asthma. However, during the first episode of wheezing, it is
difficult to distinguish bronchiolitis from asthma [110]. (See "Virus-induced wheezing
and asthma: An overview" and "Wheezing phenotypes and prediction of asthma in
young children" and "Approach to wheezing in infants and children".)
Bacterial pneumonia It can be difficult to distinguish bacterial pneumonia from
bronchiolitis in young children because the symptoms and signs of both conditions
are nonspecific; children with bacterial pneumonia may be more ill-appearing (eg,
higher fever), but clinical features cannot reliably differentiate bacterial from viral
lower respiratory tract infection (table 2). (See "Community-acquired pneumonia in
children: Clinical features and diagnosis", section on 'Diagnosis'.)
Chronic pulmonary disease Chronic underlying pulmonary conditions should be
suspected in children with prolonged or recurrent symptoms, such as recurrent
wheezing, failure to thrive, recurrent aspiration, stridor, or recurrent respiratory
infection. (See "Assessment of stridor in children" and "Approach to the child with
recurrent infections" and "Failure to thrive (undernutrition) in children younger than
two years: Etiology and evaluation", section on 'Etiology'.)
Children with underlying pulmonary disease may have a superimposed acute episode
of bronchiolitis and, in some cases, the underlying disorder is unrecognized before
the acute episode. The clinical course of bronchiolitis in children with underlying
pulmonary disorders tends to be severe and may require prolonged hospitalization.
Foreign body aspiration Clinical features of foreign body aspiration may include
a history of choking (not always present), focal monophonic wheezing, decreased air
entry, or regional variation in aeration. A high index of suspicion should be maintained
for foreign body aspiration so that definitive treatment can be provided. (See "Airway
foreign bodies in children".)
Aspiration pneumonia Aspiration pneumonia may occur secondary to
gastroesophageal reflux disease and/or swallowing dysfunction. It also may occur as
a complication of bronchiolitis; the risk of aspiration increases during active
bronchiolitis and resolves weeks later as tachypnea and the work of breathing
subside. Clinical features associated with aspiration may include coughing with feeds,
weak suck reflex, cyanosis during feeding, and recurrent or chronic stridor.
(See "Gastroesophageal reflux in infants" and "Aspiration due to swallowing
dysfunction in infants and children".)
Congenital heart disease Associated clinical findings of congenital heart disease
may include failure to thrive, poor peripheral perfusion, and abnormalities on cardiac
examination (eg, pathologic heart murmur, abnormal second heart sound, gallop, rub,
active precordium). (See "Suspected heart disease in infants and children: Criteria for
referral".)
Children with underlying cardiac conditions may have a superimposed acute episode
of bronchiolitis and, in some cases, the underlying disorder is unrecognized before
the acute episode. The clinical course of bronchiolitis in children with underlying
cardiac disorders tends to be severe and may require prolonged hospitalization.
Heart failure Associated clinical findings of heart failure in infants may include
easy fatigue and/or diaphoresis with feeding, poor weight gain, heart murmur or
gallop rhythm, and hepatomegaly. (See "Heart failure in children: Etiology, clinical
manifestations, and diagnosis", section on 'Clinical manifestations'.)
Vascular rings Although stridor is more common, children with vascular rings may
also have wheezing (typically with pulmonary artery slings). Anterior bowing of the
trachea in the lateral chest radiograph may be a clue, but other modalities
(barium contrast esophagogram, bronchoscopy, magnetic resonance angiography)
usually are necessary for definitive diagnosis. (See "Vascular rings and slings",
section on 'Clinical manifestations'.)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or email these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

Basics topic (see "Patient education: Bronchiolitis (and RSV) (The Basics)")
Beyond the Basics topic (see "Patient education: Bronchiolitis (and RSV) in infants
and children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Bronchiolitis is broadly defined as a clinical syndrome that occurs in children <2


years of age and is characterized by upper respiratory symptoms (eg, rhinorrhea)
followed by lower respiratory infection with inflammation, which results in wheezing
and or crackles (rales). (See 'Definition' above and 'Clinical features' above.)
Bronchiolitis typically is caused by a viral infection. Respiratory syncytial virus is the
most common cause followed by rhinovirus; less common causes include
parainfluenza virus, human metapneumovirus, influenza virus, adenovirus,
coronaviruses, and human bocavirus. (See 'Microbiology' above and "Respiratory
syncytial virus infection: Clinical features and diagnosis".)
Bronchiolitis typically affects infants and children younger than two years, principally
during the fall and winter. Risk factors for severe disease and/or complications include
gestational age 36 weeks, age <12 weeks, chronic pulmonary disease, congenital
and anatomic defects of the airways, hemodynamically significant congenital heart
disease, immunodeficiency, and neurologic disease. (See 'Epidemiology' above
and 'Risk factors for severe disease' above.)
The evaluation of infants and young children with suspected bronchiolitis generally
requires only history and physical examination. Chest radiographs and laboratory
tests are not necessary for diagnosis but may be warranted to evaluate
complications, comorbid infections, or other conditions in the differential diagnosis.
(See 'Evaluation' above.)
Bronchiolitis is diagnosed clinically. Characteristic features include a viral upper
respiratory prodrome followed by increased respiratory effort (eg, tachypnea, nasal
flaring, chest retractions) and wheezing and/or rales in children younger than two
years. (See 'Clinical diagnosis' above and 'History' above and 'Examination' above.)
Severe bronchiolitis is indicated by persistently increased respiratory effort
(tachypnea; nasal flaring; intercostal, subcostal, or suprasternal retractions;
accessory muscle use; grunting), hypoxemia, apnea, or acute respiratory failure.
Children with severe disease usually require hospitalization for respiratory and fluid
support. (See 'Severity assessment' above and "Bronchiolitis in infants and children:
Treatment, outcome, and prevention", section on 'Severe bronchiolitis'.)
The differential diagnosis of bronchiolitis includes recurrent viral-triggered wheezing
or recurrent wheezing, pneumonia, foreign body aspiration, chronic pulmonary
disease, aspiration pneumonia, congenital heart disease, heart failure, and vascular
ring. Clinical features (eg, lack of preceding upper respiratory tract symptoms,
witnessed episode of choking, differential aeration, poor growth) may help to
distinguish some of these conditions from bronchiolitis; for others, radiographic or
laboratory studies may be necessary. (See 'Differential diagnosis' above.)

Neumona bacteriana

Community-acquired pneumonia in children: Outpatient treatment

Author:
William J Barson, MD
Section Editors:
Morven S Edwards, MD
George B Mallory, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jan 13, 2016.

INTRODUCTION Community-acquired pneumonia (CAP) is defined as an acute


infection of the pulmonary parenchyma in a patient who has acquired the infection in the
community, as distinguished from hospital-acquired (nosocomial) pneumonia. CAP is a
common and potentially serious illness with considerable morbidity.

The Pediatric Infectious Diseases Society/Infectious Diseases Society of America and the
British Thoracic Society have developed clinical practice guidelines for the evaluation and
treatment of CAP in children [1,2].

The outpatient treatment of CAP in infants and children will be reviewed here. Neonatal
pneumonia and inpatient treatment of pneumonia are discussed separately, as are the
epidemiology, etiology, clinical features, and diagnosis. (See "Neonatal
pneumonia" and "Pneumonia in children: Inpatient treatment" and "Pneumonia in children:
Epidemiology, pathogenesis, and etiology" and "Community-acquired pneumonia in
children: Clinical features and diagnosis".)

INDICATIONS FOR HOSPITALIZATION The decision to hospitalize a child with CAP is


individualized based upon age, underlying medical problems, and clinical factors including
severity of illness (table 1) [1-3]. Hospitalization generally is warranted for infants younger
than three to six months of age, unless a viral etiology or Chlamydia trachomatis is
suspected and they are normoxemic and relatively asymptomatic. Hospitalization is also
warranted for a child of any age whose family cannot provide appropriate care and assure
compliance with the therapeutic regimen. Additional indications for hospitalization include
[1,2]:

Hypoxemia (oxygen saturation <90 percent in room air at sea level)


Dehydration, or inability to maintain hydration orally; inability to feed in an infant
Moderate to severe respiratory distress: Respiratory rate >70 breaths per minute for
infants <12 months of age and >50 breaths per minute for older children; retractions;
nasal flaring; difficulty breathing; apnea; grunting
Toxic appearance (more common in bacterial pneumonia and may suggest a more
severe course) [4]
Underlying conditions that may predispose to a more serious course of pneumonia
(eg, cardiopulmonary disease, genetic syndromes, neurocognitive disorders), may be
worsened by pneumonia, even viral pneumonia (eg, metabolic disorder) or may
adversely affect response to treatment (eg, immunocompromised host)
Complications (eg, effusion/empyema) (see "Epidemiology; clinical presentation;
and evaluation of parapneumonic effusion and empyema in
children" and "Management and prognosis of parapneumonic effusion and empyema
in children")
Suspicion or confirmation that CAP is due to a pathogen with increased virulence,
such as Staphylococcus aureus or group A streptococcus
Failure of outpatient therapy (worsening or no response in 48 to 72 hours)
(see 'Treatment failure' below)

EMPIRIC THERAPY

Overview Children with CAP who are treated in the outpatient setting typically are
treated empirically; tests to identify a microbiologic etiology are not recommended for most
children who are well enough to be treated in the outpatient setting [1,2]. Decisions
regarding empiric therapy are complicated by the substantial overlap in the clinical
presentation of bacterial and nonbacterial pneumonias [2,5,6]. Treatment decisions are
usually based upon algorithms that include patient age, epidemiologic and clinical
information, and diagnostic laboratory and imaging studies (if such studies were obtained)
(table 2 and table 3) [4]. Consultation with a specialist in infectious disease may be helpful
in children with medication allergies or comorbid conditions. (See "Community-acquired
pneumonia in children: Clinical features and diagnosis" and "Pneumonia in children:
Epidemiology, pathogenesis, and etiology", section on 'Etiologic agents'.)

There are few randomized controlled trials to guide the choice of empiric antibiotics in
children with CAP. Factors that must be considered include the spectrum of likely
pathogens, antimicrobial susceptibility, simplicity, tolerability, palatability, safety, and cost
[7]. The recommendations of most guidelines are based upon observations regarding the
susceptibility of the most likely pathogen or pathogens, rather than on evidence of the
superiority of one antibiotic over another [1,2]. The clinical response to the most commonly
used antimicrobials appears to be similar, regardless of etiology [8-10]. The response
within the first 48 to 72 hours of empiric therapy (or lack of therapy if a viral etiology is
most likely) helps to determine whether additional evaluation or changes in therapy are
necessary. (See 'Monitoring response' below.)

Children <5 years

Neonates The treatment of neonatal pneumonia is discussed separately.


(See "Neonatal pneumonia".)

One to six months Infants younger than three to six months of age with suspected
bacterial CAP or who are hypoxemic (oxygen saturation <90 percent in room air at sea
level) should be admitted to the hospital for empiric therapy. (See "Pneumonia in children:
Inpatient treatment", section on 'Empiric therapy'.)

In afebrile infants one to four months of age with CAP, the most likely bacterial pathogen
is C. trachomatis (ie, "afebrile pneumonia of infancy") [4,11]. Infants who are thought to
have afebrile pneumonia of infancy can be treated in the outpatient setting if they are not
hypoxemic and remain afebrile [4]. (See "Chlamydia trachomatis infections in the
newborn", section on 'Treatment'.)

Bordetella pertussis is a less common, but more severe, cause of pneumonia in young
infants; fever may or may not be present. Like C. trachomatis, B. pertussis is susceptible
to the macrolides [4]. However, young infants who are thought to have B. pertussis-
associated pneumonia should be admitted to the hospital because they are at risk for
complications (eg, hypoxia, apnea, pulmonary hypertension, etc). (See "Pertussis infection
in infants and children: Clinical features and diagnosis", section on 'Infants' and "Pertussis
infection in infants and children: Treatment and prevention", section on 'Hospitalization'.)

Six months to five years

Suspected viral etiology Viral etiologies predominate during early childhood. Viral
pneumonia (suggested by gradual onset, preceding upper respiratory tract symptoms,
diffuse findings on auscultation, lack of toxic appearance (table 3)) should not be treated
with antibiotics. Antiviral agents generally are not used for viral pneumonia in the
outpatient setting, with the exception of neuraminidase inhibitors for influenza pneumonia.
(See "Community-acquired pneumonia in children: Clinical features and diagnosis",
section on 'Clues to etiology' and "Pneumonia in children: Epidemiology, pathogenesis,
and etiology", section on 'Etiologic agents' and "Seasonal influenza in children: Prevention
and treatment with antiviral drugs", section on 'Antiviral therapy'.)

Infants and young children with known or suspected chronic disease (eg, cardiopulmonary
disease, neuromuscular disease, etc) are at increased risk for severe or complicated viral
lower respiratory tract infection (LRTI). If such children are not admitted to the hospital,
they merit close monitoring in the outpatient setting.

Suspected influenza In children with suspected influenza who are at increased


risk of complications (table 4), initiation of antiviral treatment is recommended as soon
as possible; laboratory confirmation should not delay initiation of antiviral therapy. The
diagnosis and treatment of influenza in children are discussed separately.
(See "Seasonal influenza in children: Prevention and treatment with antiviral drugs",
section on 'Antiviral therapy' and "Seasonal influenza in children: Clinical features and
diagnosis", section on 'Clinical features'.)

Suspected bacterial etiology Streptococcus pneumoniae is the most frequent cause


of "typical" bacterial pneumonia in children of all ages [1,2]. Bacterial pneumonia in
preschool children usually causes more severe infection, with abrupt onset and moderate
to severe respiratory distress, which may require inpatient therapy. (See 'Indications for
hospitalization' above and "Pneumonia in children: Inpatient treatment", section on 'Empiric
therapy'.)
For children younger than five years who are thought to have bacterial CAP based upon
clinical presentation, examination findings, and supportive radiographic or laboratory data
if obtained (eg, lobar consolidation on radiograph, white blood cell count
[WBC] >15,000/microL, C-reactive protein >35 to 60 mg/L [3.5 to 6 mg/dL] (table 3)), but
do not require inpatient therapy, amoxicillin is usually considered the drug of choice
[1,2,12]. We suggest high dose amoxicillin (90 to 100 mg/kg per day divided into two or
three doses; maximum dose 4 g/day) (table 2).

Amoxicillin is preferred because it is effective against the majority of bacterial pathogens


for CAP in this age group, is well tolerated, and is inexpensive [1,2]. The higher dose of
amoxicillin is suggested because of the concern for antibiotic-resistant S.
pneumoniae isolated from patients with community-acquired respiratory tract infections
[13,14]. Amoxicillin is more active in vitro than any of the oral cephalosporins against these
isolates. Universal infant immunization with the 7-valent pneumococcal conjugate vaccine
(PCV7) resulted in a decreased prevalence of penicillin resistant pneumococci. However, it
was associated with the emergence of antibiotic-resistant invasive serotypes, some of
which are included in the 13-valent pneumococcal conjugate vaccine (PCV13) (eg,
serotype 19A) [1]. The effects of PCV13 on antibiotic resistance are preliminary and
suggest an increasing susceptibility to penicillin and ceftriaxone. The proportion of total
isolates with penicillin MICs >2 mcg/mL reported by the Pediatric Multicenter
Pneumococcal Surveillance Group decreased from 21.2 to 8.2 percent between 2008-
2009 and 2011 [15]. A similar decrease was seen in isolates with a ceftriaxone MIC
>1 mcg/mL. Pending additional data confirming this trend, we continue to suggest high-
dose rather than standard dose amoxicillin (ie, 40 to 45 mg/kg per day) when amoxicillin is
used to treat CAP in children. (See "Resistance of Streptococcus pneumoniae to beta-
lactam antibiotics" and "Resistance of Streptococcus pneumoniae to the macrolides,
azalides, lincosamides, and ketolides".)

Although there are prospective, comparative data supporting the efficacy of twice daily
dosing of amoxicillin for the treatment of acute otitis media [16-18], similar data are not
available for documented pneumococcal pneumonia in children. Unless the etiologic agent
is identified as a S. pneumoniae isolate with a minimum inhibitory concentration (MIC) of
<2 mcg/mL, dividing the total daily 90 to 100 mg/kg dose of amoxicillin into three doses
may be warranted. Twice daily dosing for pneumonia due to a S. pneumoniae isolate with
an MIC of 2 mcg/mL is predicted to achieve a clinical and microbiologic cure in only 65
percent of children, whereas the same total daily dose divided in three equal portions is
predicted to achieve a cure in 90 percent [19].

For children with non-type 1 hypersensitivity reactions to penicillin (table 5), a second- or
third-generation cephalosporin (eg, cefdinir) is an acceptable alternative to amoxicillin [1].
For children with type 1 hypersensitivity reactions (table 5) to penicillin, clindamycin or a
macrolide may be used [1,2]. However, if local resistance rates are high for clindamycin
and macrolides, levofloxacin or linezolid may be preferable. Doses are provided in the
table (table 2).

For the infant or child who is suspected to have bacterial CAP and is unable to tolerate
liquids at the time of presentation, a single initial dose of ceftriaxone (50 to 75 mg/kg) may
be administered intramuscularly or intravenously before starting oral antibiotics [20,21].
Administration of intramuscular ceftriaxone to children with uncomplicated CAP who are
able to tolerate liquids is expensive and provides no benefit over oral antibiotics.

Suspected atypical pneumonia Mycoplasma


pneumoniae and Chlamydophilapneumoniae are less common than S. pneumoniae in
children younger than five years with CAP [5]. However, they can occur in this age group
and should be considered in children without a pneumonia-associated complication who
fail to improve after 48 to 72 hours of empiric therapy for S. pneumoniae (eg, amoxicillin),
at which time a macrolide could be added or substituted (table 2). (See 'Treatment
failure' below.)

Children 5 years

Suspected typical or atypical bacterial etiology S. pneumoniae is the most frequent


cause of "typical" bacterial pneumonia in children of all ages [1,2]. However, in otherwise
healthy children five years and older with CAP who are not ill enough to require
hospitalization, M. pneumoniae and C. pneumoniae are the most likely pathogens
[4,11,22].

We suggest macrolide antibiotics for initial empiric therapy for CAP in children older than
five years who are treated as outpatients [1,4]. However, the prevalence of macrolide-
resistant M. pneumoniae is increasing in some geographic regions, including Asia, Europe,
Israel, and the United States [23-31]. The reported prevalence of resistance among M.
pneumoniae isolates ranges from approximately 10 percent in the United States to 90
percent in China and some parts of Japan [25,28,32,33]. Alternative agents
include levofloxacin and doxycycline [1]. The long-held concern for enamel staining
associated with doxycycline in children younger than eight years use is unfounded [34].
The British Thoracic Society clinical practice guideline suggests amoxicillin as the first-line
therapy for children of all ages [2]. Doses are provided in the table (table 2).

Among the macrolide antibiotics, clarithromycin and azithromycin have a more convenient
dosing schedule and fewer side effects than erythromycin, but erythromycin is less
expensive [8,35,36]. Macrolide antibiotics may provide coverage for S. pneumoniae, which
is the most frequent typical bacterial pathogen for all age groups [37-39]. However,
approximately 40 to 50 percent of S. pneumoniae isolates are resistant to macrolides.
Failure to respond to macrolide therapy may indicate the development of a complication, a
macrolide-resistant pathogen, and/or the need to alter therapy to provide better
pneumococcal coverage. (See 'Treatment failure' below.)
Given the significant resistance of S. pneumoniae to macrolides, fluoroquinolones
(eg, levofloxacin, moxifloxacin) are another reasonable alternative for the outpatient
treatment of CAP. In addition to their excellent gram-negative spectrum, the
fluoroquinolones are active against a number of the pathogens responsible for CAP,
including beta-lactam-susceptible and non-susceptible S. pneumoniae, M. pneumoniae,
and C. pneumoniae [40]. However, S. pneumoniae resistant to levofloxacin has been
identified [41].

Suspected influenza Initiation of antiviral treatment for influenza (eg, oseltamivir) as


soon as possible is recommended for children with suspected influenza who are at high
risk for complications of influenza pneumonia (table 4); laboratory confirmation should not
delay initiation of antiviral therapy. The diagnosis and treatment of influenza in children are
discussed separately. (See "Seasonal influenza in children: Prevention and treatment with
antiviral drugs", section on 'Antiviral therapy'.)

Suspected aspiration pneumonia Community-acquired aspiration pneumonia is


usually treated with amoxicillin-clavulanate. Clindamycin is an alternative for patients
allergic to penicillin. Doses are provided in the table (table 2). In neurologically
compromised adolescents who may be prone to aspiration events, empiric treatment
with moxifloxacin (400 mg once per day) is an alternative. Moxifloxacin is active against
anaerobic bacteria, as well as the usual treatable causes of CAP: S. pneumoniae, M.
pneumoniae, and C. pneumoniae. Fluoroquinolone antibiotics generally are not
recommended for children younger than 18 years of age when there is a safe and effective
alternative. (See "Fluoroquinolones", section on 'Use in children'.)

Duration Few randomized controlled trials have been performed to determine the
appropriate duration of antimicrobial therapy in radiographically confirmed childhood
pneumonia [2]. Current practice in the developed world determines the duration of therapy
based upon the age of the host, likely causative agent, and severity of disease:

We suggest that infants 4 months and children with uncomplicated pneumonia


suspected or confirmed to be caused by routine pathogens (ie, S. pneumoniae, M.
pneumoniae, C. pneumoniae) be treated for 7 to 10 days; the course
of azithromycin is five days [1,8]
The duration of treatment for C. trachomatis pneumonia in young infants is
discussed separately (see "Chlamydia trachomatis infections in the newborn", section
on 'Treatment')

A meta-analysis found three days of oral antimicrobial therapy to be as effective as five


days for nonsevere CAP in children aged 2 to 59 months [42]. However, the studies
included in the meta-analysis were performed in developing countries, where it is not
feasible to perform radiographs or evaluation for a microbiologic etiology; pneumonia was
diagnosed by the World Health Organization (WHO) criteria, which are based on clinical
findings and respiratory rate thresholds. In another study, only 14 percent of children
diagnosed with nonsevere pneumonia by the WHO criteria had radiographic evidence of
pneumonia [43]. Many of the children in the meta-analysis probably had viral pneumonia,
for which antibiotic therapy is not warranted. This is supported by a subsequent
randomized trial in which the clinical outcomes did not differ for children aged 2 to 59
months who were diagnosed with nonsevere pneumonia by the WHO criteria and treated
for three days with amoxicillin versus placebo [44].

In a subsequent randomized trial in a developed country, 4 of 10 children who received


three days of outpatient treatment (amoxicillin 80 mg/kg per day divided in three doses) for
radiologically confirmed CAP required rescue therapy or hospitalization versus none of 12
children treated for 10 days [45]. In the second stage of the trial, five days of treatment
(amoxicillin 80 mg/kg per day divided in three doses) was as effective as 10 days in
preventing the need for rescue therapy or hospitalization, but with fewer than 60 patients in
each arm, the study may have been underpowered to detect a difference. Additional,
larger studies are necessary to confirm these results before we suggest five days of
therapy for uncomplicated CAP.

Monitoring response Children with CAP who are treated as outpatients (including
those who were not initially treated with antibiotics) should have follow-up within 24 to 48
hours [1,2]. Follow-up may be performed by phone. Children with CAP who are
appropriately treated generally show signs of improvement within 48 to 72 hours.

Treatment failure Among patients who do not improve as anticipated, the following
possibilities must be considered [1,2,14,46]:

Alternative or coincident diagnoses (eg, foreign body aspiration) (see "Community-


acquired pneumonia in children: Clinical features and diagnosis", section on
'Differential diagnosis')
Development of complications (see "Community-acquired pneumonia in children:
Clinical features and diagnosis", section on 'Complications')
Ineffective antibiotic coverage (lack of coverage for the actual etiology or resistant
organism)

Worsened condition Patients whose condition has worsened require additional


evaluation and hospitalization. They also should undergo radiologic evaluation to look for
the development of complications. Laboratory tests should be performed to try to establish
a microbiologic diagnosis. (See "Community-acquired pneumonia in children: Clinical
features and diagnosis", section on 'Laboratory evaluation' and "Pneumonia in children:
Inpatient treatment", section on 'Hospitalization'.)

Failure to improve In patients who fail to improve, but have not worsened, it may be
reasonable to add or strengthen coverage for S. pneumoniae or atypical bacteria if these
organisms were not covered in the initial therapy (table 2) [1,4]. It is also important to
consider underlying or comorbid conditions (eg, immunodeficiency, anatomic abnormality).
(See "Community-acquired pneumonia in children: Clinical features and diagnosis",
section on 'Differential diagnosis'.)

Patients initially treated with beta-lactam antibiotics Failure to improve while


being treated with a beta-lactam antibiotic (amoxicillin or cephalosporin) may indicate
infection caused by penicillin-resistant S. pneumoniae or S. aureus (either methicillin-
susceptible or -resistant) [47]. If penicillin-resistant S. pneumoniae is suspected, a
change in antibiotic therapy to clindamycin or linezolid may be
indicated. Levofloxacin is an option if there is a high rate of pneumococcal resistance
to clindamycin. Doses are provided in the table (table 2). If S. aureus is suspected
based upon a rapidly worsening clinical course with progressive radiographic findings
that may include multiple patchy alveolar infiltrates coalescing to form large
consolidated areas, in a young, immunocompetent host often with a preceding viral
illness, the child should be hospitalized given the increased risk of complications (eg,
necrosis, empyema, pneumatocele) and death. (See "Pneumonia in children:
Inpatient treatment".)
Patients initially treated with macrolide antibiotics Failure to improve while
being treated with a macrolide antibiotic may indicate the need to perform a
diagnostic test (eg, PCR) to confirm an M. pneumoniae etiologic
diagnosis and/or alter therapy to provide better coverage for S. pneumoniae or
macrolide-resistant M. pneumoniae. (See "Mycoplasma pneumoniae infection in
children", section on 'Approach to laboratory confirmation'.)
For patients initially treated with macrolides, better pneumococcal coverage can be
achieved by the addition of high-dose amoxicillin, a cephalosporin
(eg, cefdinir, cefpodoxime), or clindamycin. Among these options, we prefer high-
dose amoxicillin because it is well tolerated and inexpensive. Amoxicillin and
cephalosporins may provide coverage for other potential, albeit less common causes,
of bacterial pneumonia in older children (eg, Haemophilus influenzae type b,
nontypeable H. influenzae, Moraxella catarrhalis, group A streptococcus) [11].
Clindamycin provides coverage for most S. aureus infections. For children who have
type 1 hypersensitivity (table 5) to penicillins, a fluoroquinolone
(eg, levofloxacin, moxifloxacin) may be used. Tetracyclines (eg, doxycycline) and
fluoroquinolones can be used if macrolide-resistant M. pneumoniae is suspected [48].
Fluoroquinolones also provide coverage for most typical bacterial etiologies of CAP
except S aureus. Doses are provided in the table (table 2). (See "Mycoplasma
pneumoniae infection in children", section on 'Treatment'.)

SUPPORTIVE CARE The families of children who are managed as outpatients should
be instructed regarding management of fever and pain, maintaining adequate hydration,
and identification of deterioration (eg, persistent fever, increased retractions, use of
accessory muscles, grunting, inability to feed) [2].
Children with pneumonia usually have fever and may have pleuritic chest pain,
which can lead to shallow breathing and impaired ability to cough [2]. Administration
of antipyretics and/or analgesics can be used to keep the child comfortable. Adequate
pain control may promote coughing, which facilitates airway clearance. Antitussives
should be avoided as none have been found to be effective in pneumonia [49].
Symptomatic treatment of cough is discussed separately. (See "The common cold in
children: Management and prevention", section on 'Cough'.)
Infants and young children with respiratory distress may be better able to maintain
hydration if fluids are provided in small volumes more frequently than in large
volumes less often.
Gentle suction of the nares may be helpful in infants and children whose nares are
blocked by nasal secretions.

FOLLOW-UP

Clinical course Children who are appropriately treated for CAP gradually improve with
time [50]. The symptoms associated with viral lower respiratory tract infections, particularly
cough, usually resolve in less than one month in healthy infants and children, but may
rarely last for up to three to four months. Cough may persist for as long as three to four
months after viral pneumonia or pertussis. Children who are recovering from typical or
atypical bacterial pneumonia may continue to cough for several weeks and have moderate
dyspnea on exertion for two to three months [50].

Radiographs Follow-up radiographs are not necessary in asymptomatic children with


uncomplicated CAP. Follow-up radiographs two to three weeks after completion of therapy
may be helpful in assessing alternate diagnoses or coincident conditions in children with
recurrent pneumonia, persistent symptoms, severe atelectasis, unusually located
infiltrates, or round pneumonia (ie, pulmonary consolidation that appears to be spherical)
[1,2,51]. Conditions that must be considered if a round pneumonia fails to resolve on
follow-up imaging include congenital lung sequestration, metastatic Wilms tumor, cavitary
necrosis, pleural pseudocyst, and primary lung carcinoma [51-55]. (See "Community-
acquired pneumonia in children: Clinical features and diagnosis", section on 'Differential
diagnosis'.)

Several studies have evaluated the utility of follow-up radiographs in cohorts of children
with acute radiologically proven CAP [56-61]. Three of the studies included clinical as well
as radiologic follow-up at three to seven weeks after initial diagnosis [56-59]. In each of
these studies, follow-up radiographs were normal or improved in asymptomatic children.
Residual findings, even when present, did not result in additional therapy.

PROGNOSIS Most otherwise healthy children who develop pneumonia recover without
any long-term sequelae [39]. Although some prospective studies suggest that pneumonia
in childhood is associated with subsequent symptoms of asthma that may persist into
adulthood, it is not clear whether this is related to unrecognized asthma at the time of
presentation with pneumonia or a tendency to develop asthma after CAP [62,63].

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Community-acquired pneumonia in children".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Pneumonia in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

Community-acquired pneumonia (CAP) is defined as an acute infection of the


pulmonary parenchyma in a patient who has acquired the infection in the community.
The clinical manifestations and diagnosis of CAP are discussed separately.
(See "Community-acquired pneumonia in children: Clinical features and diagnosis".)
The decision to hospitalize a child with pneumonia must be individualized and is
based upon age, underlying medical problems, and severity of illness (table 1).
(See 'Indications for hospitalization' above.)
Children with CAP who are treated in the outpatient setting are treated empirically. It
is not necessary to identify a microbiologic etiology in children who are well enough to
be treated as outpatients. Decisions regarding empiric antimicrobial therapy for CAP
in children are usually based upon age unless there are other overriding
epidemiologic or clinical factors to suggest a specific etiologic agent.
(See 'Overview' above.)
Infants younger than three to six months of age with suspected bacterial CAP or
who are hypoxemic should be admitted to the hospital for management. Afebrile
infants one to four months of age who are thought to have afebrile pneumonia of
infancy (eg, Chlamydia trachomatis) can be treated in the outpatient setting if they are
not hypoxemic and remain afebrile. (See "Pneumonia in children: Inpatient
treatment" and "Chlamydia trachomatis infections in the newborn".)
We recommend that empiric antibiotic therapy for CAP in children six months to five
years of age who are thought to have bacterial pneumonia (eg, abrupt onset,
moderate to severe respiratory distress, and supportive laboratory data if obtained
(table 3)) include coverage for Streptococcus pneumoniae (table 2) (Grade 1B).
(See 'Children <5 years' above.)
We suggest that empiric antibiotic therapy for CAP in children 5 years include
coverage for atypical bacteria (Grade 2B). (See 'Children 5 years' above.)
In infants and children six months and older, the usual duration of antimicrobial
therapy is five days for azithromycin and 7 to 10 days for other agents.
(See 'Duration' above.)
Children who are treated for CAP as outpatients should have follow-up within 24 to
48 hours. Those whose condition has worsened at follow-up should be evaluated for
potential complications and hospitalized. (See 'Monitoring response' above
and "Pneumonia in children: Inpatient treatment".)
Children recovering from CAP may continue to cough for several weeks to four
months, depending upon the etiology. Those recovering from typical or atypical
bacterial pneumonia may have moderate dyspnea on exertion for two to three
months. (See 'Clinical course' above.)
Follow-up radiographs in children with uncomplicated CAP who remain
asymptomatic are not needed. Follow-up radiographs two to three weeks after
completion of therapy may be helpful in children with recurrent pneumonia, persistent
symptoms, severe atelectasis, unusually located infiltrates, or round pneumonia.
(See 'Radiographs' above.)
Most otherwise healthy children who develop pneumonia recover without any long-
term sequelae. (See 'Prognosis' above.)

neumonia in children: Inpatient treatment

Author:
William J Barson, MD
Section Editors:
Morven S Edwards, MD
George B Mallory, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Dec 02, 2016.

INTRODUCTION Community-acquired pneumonia (CAP) is defined as an acute


infection of the pulmonary parenchyma in a patient who has acquired the infection in the
community, as distinguished from hospital-acquired (nosocomial) pneumonia. CAP is a
common and potentially serious illness with considerable morbidity.

The inpatient treatment of CAP and hospital-acquired pneumonia in children will be


reviewed here. The outpatient treatment of CAP is discussed separately, as are the
epidemiology, etiology, clinical features, and diagnosis. (See "Community-acquired
pneumonia in children: Outpatient treatment" and "Pneumonia in children: Epidemiology,
pathogenesis, and etiology" and "Community-acquired pneumonia in children: Clinical
features and diagnosis".)

The recommendations provided below are largely consistent with practice guidelines
provided by The Pediatric Infectious Diseases Society/Infectious Diseases Society of
America and the British Thoracic Society [1,2].

HOSPITALIZATION

Indications The decision to hospitalize a child with community-acquired pneumonia


(CAP) is individualized based upon age, underlying medical problems, and clinical factors
including severity of illness (table 1) [1-3]. Hospitalization generally is warranted for infants
younger than three to six months of age, unless a viral etiology or Chlamydia
trachomatis is suspected and they are not hypoxemic and relatively asymptomatic.
Hospitalization is also warranted for a child of any age whose family cannot provide
appropriate care and assure compliance with the management plan. Additional indications
for hospitalization include [1,2]:

Hypoxemia (oxygen saturation [SpO2] <90 percent in room air at sea level)
Dehydration, or inability to maintain hydration orally; inability to feed in an infant
Moderate to severe respiratory distress: Respiratory rate >70 breaths/minute for
infants <12 months of age and >50 breaths per minute for older children; retractions;
nasal flaring; difficulty breathing; apnea; grunting
Toxic appearance (more common in bacterial pneumonia and may suggest a more
severe course) [4]
Underlying conditions that may predispose to a more serious course of pneumonia
(eg, cardiopulmonary disease, genetic syndromes, neurocognitive disorders), may be
worsened by pneumonia (eg, metabolic disorder) or may adversely affect response to
treatment (eg, immunocompromised host)
Complications (eg, effusion/empyema)
Suspicion or confirmation that CAP is due to a pathogen with increased virulence,
such as Staphylococcus aureus or group A Streptococcus
Failure of outpatient therapy (worsening or no response in 48 to 72 hours)

Indications for intensive care The decision to treat a child with pneumonia in an
intensive care setting is individualized, based upon clinical, laboratory, and radiologic
findings. Treatment in an intensive care setting generally is warranted for children who
manifest [1,2]:

The need for ventilatory support beyond that which can be provided outside the
intensive care unit (eg, mechanical ventilation, noninvasive positive pressure
ventilation, failure to maintain oxygen saturation [SpO2] >92 percent in FiO2 >0.5)
Signs of impending respiratory failure (lethargy, increasing work of
breathing, and/or exhaustion with or without hypercarbia)
Recurrent apnea or slow irregular respirations
Cardiovascular compromise with progressive tachycardia and/or hypotension that
requires or is refractory to fluid management

Care in the intensive care unit also may be warranted for children with two or more of the
following [1]:

Respiratory rate >70 breaths/minute for infants <12 months of age and
>50 breaths/minute for older children
Apnea
Increased work of breathing (retractions, dyspnea, nasal flaring, grunting)
PaO2/FiO2 ratio <250
Multilobar infiltrates
Altered mental status
Hypotension
Pleural effusion
Comorbid condition (eg, sickle cell disease, immune deficiency,
immunosuppression)
Unexplained metabolic acidosis
Pediatric Early Warning Score >6 [5]

Infection control CAP can be caused by a variety of microbial agents requiring a


variety of infection-control measures [6]. If possible, rapid diagnostic tests should be
performed at the time of admission, to facilitate decisions regarding appropriate
precautions. (See "Community-acquired pneumonia in children: Clinical features and
diagnosis", section on 'Rapid diagnostic tests'.)

Hand washing is the single most important procedure to prevent the spread of infection.
Additional infection control measures depend upon the likely pathogen(s), as follows [6,7]:

Respiratory syncytial and parainfluenza viruses Gown and gloves (ie, contact
precautions)
Influenza virus, group A Streptococcus (for the first 24 hours of treatment),
methicillin-susceptible S. aureus, Bordetella pertussis (until patient has received five
days of effective therapy), and Mycoplasma pneumoniae Mask within 3 feet (ie,
droplet precautions)
Adenovirus Contact and droplet precautions
Methicillin-resistant S. aureus and other multidrug resistant organisms Special
organism precautions; contact and droplet precautions and dedicated patient
equipment

These precautions are discussed separately (see "Infection prevention: Precautions for
preventing transmission of infection"). Guidelines for hand hygiene in healthcare settings
can be accessed through the Centers for Disease Control and Prevention.

SUPPORTIVE CARE Supportive care includes ensuring adequate antipyresis,


analgesia, respiratory support, and hydration.

Antipyresis and analgesia Children hospitalized with pneumonia usually have fever
and may have pleuritic chest pain, which can lead to shallow breathing and impaired ability
to cough. Administration of antipyretics and/or analgesics (eg, acetaminophen, ibuprofen)
can be used to keep the child comfortable; opioid analgesia is rarely necessary in children
without a chest tube in place. Adequate pain control may promote coughing, which
facilitates airway clearance. Antitussives should be avoided as none have been found to
be effective in pneumonia [8]. Symptomatic treatment of cough is discussed separately.
(See "The common cold in children: Management and prevention", section on 'Cough'.)

Respiratory support Children hospitalized with pneumonia should receive ventilatory


support as indicated by their clinical condition [1,2]. A supported sitting position may help
to expand the lungs and improve respiratory symptoms [2].

We suggest that children with oxygen saturation [SpO2] <95 percent in room air be treated
with supplemental oxygen to maintain oxygen saturation 95 percent while they are in
respiratory distress. Different thresholds for supplemental oxygen are suggested by other
experts (eg, the British Thoracic Society guidelines suggest supplemental oxygenation to
maintain oxygenation saturation >92 percent) [2]. Gentle bulb suction of the nares may be
helpful in infants and children whose nares are blocked with secretions. Minimal handling
seems to reduce oxygen requirements. (See "Continuous oxygen delivery systems for
infants, children, and adults".)

In children who are severely ill, it may be necessary to monitor carbon dioxide tension via
blood gas analysis in addition to oxygen saturation (SpO2) by oximetry. Hypercarbia is an
important sign of impending respiratory failure, particularly in the young infant who is tiring
but may have preserved oxygenation.

Fluid management Children who cannot maintain adequate fluid intake because of
breathlessness, fatigue, or risk of aspiration [9] may require intravenous fluid therapy.
Nasogastric (NG) tubes should be avoided if possible because they may compromise
breathing; if necessary, the smallest NG tube possible should be used [2].
(See "Maintenance fluid therapy in children".)

Children with pneumonia are at risk for inappropriate secretion of antidiuretic hormone
(SIADH) [10,11]. Serum electrolytes, fluid balance, and urine specific gravity should be
monitored if there is clinical suspicion of SIADH [11]. Confirmation of SIADH is discussed
separately. Isotonic, rather than hypotonic, intravenous fluids should be provided if SIADH
is suspected. (See "Pathophysiology and etiology of the syndrome of inappropriate
antidiuretic hormone secretion (SIADH)", section on 'Pulmonary
disease' and "Maintenance fluid therapy in children", section on 'Hospitalized children'.)

Chest physiotherapy Chest physiotherapy is not beneficial for children with


uncomplicated community-acquired pneumonia (CAP) [2]. In randomized and
observational studies in children and adults, chest physiotherapy had no conclusive effect
on length of hospital stay, duration of fever, or radiographic resolution [12-17].

Adjunctive glucocorticoid therapy We do not routinely provide adjunctive


glucocorticoid therapy to children hospitalized with pneumonia. Although a systematic
review and meta-analysis of randomized trials in adult patients hospitalized with CAP
found that corticosteroid therapy may be beneficial in reducing the development of acute
respiratory distress syndrome, need for mechanical ventilation, and the duration of
hospitalization [18], additional studies in children are necessary. A retrospective study
evaluating adjunctive glucocorticoid therapy for children being treated for CAP in the
outpatient setting found an association between adjunctive glucocorticoid therapy and
treatment failure in children without underlying asthma [19].

EMPIRIC THERAPY

Overview Prompt initiation of antimicrobial therapy is crucial in children with


community-acquired pneumonia (CAP). The initial treatment of children who are
hospitalized with pneumonia is empiric (table 2). Factors that must be considered include
the spectrum of likely pathogens, antimicrobial susceptibility, simplicity, tolerability,
palatability, safety, and cost [20].

The recommendations of most guidelines are based on in vitro susceptibilities of the most
likely pathogen or pathogens, rather than evidence of the superiority of one antibiotic over
another. Clinical response to empiric therapy and results of microbiologic studies, when
available, help to determine whether additional evaluation or changes in therapy are
necessary [1,2]. (See "Community-acquired pneumonia in children: Clinical features and
diagnosis", section on 'Microbiology' and 'Specific therapy' below and 'Response to
therapy' below.)

There are few randomized controlled trials to guide the choice of empiric antibiotics in
children with CAP. Decisions regarding empiric therapy are complicated by the substantial
overlap in the clinical presentation of bacterial and nonbacterial pneumonias [21-23].
Treatment decisions usually are based upon algorithms that include patient age,
epidemiologic and clinical information, and diagnostic laboratory and imaging studies
(table 2) [4]. The scope of empiric therapy (ie, narrow or broad) depends upon the severity
of illness and presence of complications. Agents other than those suggested in the table
may be more appropriate if there are clinical or epidemiologic features strongly suggestive
of a specific cause (eg, mediastinal or hilar lymphadenopathy, residence in the central
United States, and exposure to caves and/or bat guano suggestive of pulmonary
histoplasmosis) [24].

Consultation with a specialist in infectious disease may be helpful in children with


medication allergies, comorbid conditions, failure of outpatient therapy, or multiple-drug-
resistant organisms. Consultation with a pediatric pulmonologist may be helpful in children
with recurrent pneumonia. (See "Community-acquired pneumonia in children: Clinical
features and diagnosis" and "Community-acquired pneumonia in children: Outpatient
treatment", section on 'Treatment failure'.)

Etiologic clues Certain clinical and epidemiologic features can be used to determine
the most likely pathogen(s) to aid in decisions regarding empiric therapy. Because these
features often overlap, they cannot be used with complete confidence, but are helpful in
guiding empiric therapy until results of microbiologic tests are available (table 3). These
features are discussed in greater detail separately. (See "Community-acquired pneumonia
in children: Clinical features and diagnosis", section on 'Clues to etiology' and "Community-
acquired pneumonia in children: Clinical features and diagnosis", section on 'Etiologic
clues'.)

Neonates The treatment of neonatal pneumonia is discussed separately.


(See "Neonatal pneumonia".)

Viral pneumonia Most children younger than three to five years of age who are
admitted to the hospital with pneumonia have viral pneumonia (eg, respiratory syncytial
virus) [25]. This is particularly true in the absence of lobar (or lobular) infiltrate and pleural
effusion [4]. Viral pneumonia does not require antibiotic therapy, unless a mixed infection
or secondary bacterial infection is suspected. (See "Respiratory syncytial virus infection:
Treatment", section on 'Overview' and "Respiratory syncytial virus infection: Clinical
features and diagnosis", section on 'Clinical manifestations'.)

No effective antivirals are available for most viral pneumonias, with a few important
exceptions, described below.

Influenza pneumonia Initiation of antiviral treatment for influenza (eg, oseltamivir) as


soon as possible is recommended for children hospitalized with presumed influenza
pneumonia; laboratory confirmation should not delay initiation of antiviral therapy. The
diagnosis and treatment of influenza in children are discussed separately. (See "Seasonal
influenza in children: Prevention and treatment with antiviral drugs", section on 'Antiviral
therapy' and "Seasonal influenza in children: Clinical features and diagnosis", section on
'Diagnosis'.)

For children with influenza pneumonia in whom secondary bacterial pneumonia is


suspected, empiric antibiotic therapy should include coverage for S. aureus, including
methicillin-resistant S. aureus (MRSA). Coinfection with S. aureus may be particularly
severe and rapidly fatal.

Other viral pneumonias Acyclovir can be used in the treatment of pneumonia due to
herpes simplex virus (HSV) or varicella zoster virus (VZV). Ganciclovir be used in the
treatment of pneumonia due to cytomegalovirus (CMV). (See "Treatment of varicella
(chickenpox) infection", section on 'Individuals with complications'.)

Common respiratory viruses may cause serious infections in immunocompromised


children and require consideration of antiviral therapy: ribavirin for respiratory syncytial
virus (RSV) or parainfluenza and cidofovir for adenovirus. Concomitant immunoglobulin
therapy is an additional consideration: palivizumab for RSV, CMV immune globulin for
CMV, and intravenous immunoglobulin for the other viral etiologies. (See "Respiratory
syncytial virus infection: Treatment", section on 'Pharmacotherapy' and "Diagnosis,
treatment, and prevention of adenovirus infection", section on 'Treatment'.)

Uncomplicated bacterial pneumonia Streptococcus pneumoniae is the most common


bacterial cause of pneumonia in children of all ages [4,26]. Other potential bacterial
pathogens that may need to be included in empiric therapy for hospitalized children
include S. aureus, including MRSA, S. pyogenes (group A Streptococcus), Haemophilus
influenzae type b (Hib) (if unimmunized), nontypeable H. influenzae, and Moraxella
catarrhalis [2,4,26-31].

The table provides several suggested parenteral empiric antibiotic regimens


for uncomplicated bacterial pneumonia in hospitalized children when S. aureus is not a
consideration (table 2) [4,32,33]. The treatment of complicated CAP and severe CAP
(particularly when S. aureus is a consideration) are discussed below. (See 'Complicated
CAP' below and 'Severe CAP requiring ICU admission' below.)

Ampicillin or penicillin G generally provides adequate coverage for the fully immunized
child (table 4) in communities without substantial prevalence of penicillin-resistant S.
pneumoniae [1,34,35]. We suggest a third-generation cephalosporin
(eg, cefotaxime, ceftriaxone) for children younger than 12 months and those who are not
fully immunized because third-generation cephalosporins provide coverage for the beta-
lactamase producing pathogens (eg, H. influenzae and M. catarrhalis) that may occur in
these children. We also suggest third-generation cephalosporins for children with more
severe illness (table 1) because third-generation cephalosporins provide coverage for a
broader range of pathogens, including penicillin-resistant S. pneumoniae, than ampicillin
[1,36,37]. The fifth-generation parenteral cephalosporin, ceftaroline, is approved by the US
Food and Drug Administration (FDA) for treatment of community-acquired bacterial
pneumonia due to S. pneumoniae, methicillin-susceptible S. aureus (MSSA), and H.
influenzae in children 2 months of age. Although ceftaroline exhibits in vitro activity
against MRSA, clinical experience is insufficient to suggest its use when MRSA is a
consideration. In a randomized trial in children between 2 months and <18 years who were
hospitalized with CAP, ceftaroline and ceftriaxone had similar cure rates [38]. Three
children with S. aureus infection (two with MSSA recovered from sputum and one with
MRSA recovered from blood) were successfully treated with ceftaroline. However, patients
considered at risk for MRSA infection or those with sputum demonstrating a predominance
of gram-positive cocci in clusters were excluded from the trial, precluding conclusions
about efficacy in this population.

A macrolide may be added (table 2) if M. pneumoniae, C. pneumoniae, or legionellosis is


suspected. (See 'Atypical pneumonia' below.)

We suggest that children who require hospitalization for treatment of CAP be treated
initially with parenteral antibiotics. However, oral amoxicillin may be an alternative for
infants and children fully immunized against Hib and S. pneumoniae with uncomplicated
pneumonia that is not thought to be due to S. aureus. In a multicenter randomized trial,
treatment with amoxicillin was equivalent to treatment with penicillin G in children with CAP
who required hospital admission but did not have wheezing, hypotension, chronic
pulmonary conditions (other than asthma), immunodeficiency, pleural effusion requiring
drainage, or oxygen saturations <85 percent in room air [39]. The British Thoracic Society
guidelines suggest that oral antibiotics are safe and effective even for children with severe
pneumonia as long as they are able to tolerate oral fluids, are not vomiting, and do not
have signs of septicemia or complicated pneumonia [2].

Atypical pneumonia Atypical bacterial pathogens include C. trachomatis in afebrile


infants, and M. pneumoniae and C. pneumoniae in older children and adolescents. The
table provides several suggested empiric regimens for atypical bacterial pneumonia in
hospitalized children (table 2) [4,32].

For children older than four years, coverage for typical bacterial pathogens
(eg, ampicillin or a third-generation cephalosporin) may be added to empiric coverage for
atypical pathogens if there is strong evidence of a bacterial cause. Strong evidence of a
bacterial cause includes white blood cell count >15,000/microL, C-reactive protein (CRP)
>35 to 60 mg/L (3.5 to 6 mg/dL), chills, or no response to outpatient therapy with a
macrolide or doxycycline [4,40].

Fluoroquinolones (eg, levofloxacin, moxifloxacin) may be reasonable empiric therapy for


the older child and adolescent with suspected atypical pneumonia who could actually have
pneumococcal pneumonia. The fluoroquinolones also may be used in the older child or
adolescent who has a type 1 hypersensitivity (table 5) to beta-lactam antibiotics. In
addition to their excellent gram-negative spectrum, the fluoroquinolones are active against
a number of the pathogens responsible for CAP, including beta-lactam-susceptible and
nonsusceptible S. pneumoniae, M. pneumoniae (including macrolide-resistant M.
pneumoniae), and C. pneumoniae [41]. However, S. pneumoniae resistant to levofloxacin
have been identified [42].

Severe CAP

Severe CAP not requiring ICU admission Children with severe community-acquired
pneumonia (CAP) that does not require admission to the intensive care unit (ICU) (table 1)
may benefit from combination empiric therapy with a macrolide and a beta-lactam
antibiotic (eg, penicillin or third-generation cephalosporin) (table 2). Combination therapy
improves coverage for resistant organisms and mixed bacterial/atypical bacterial
infections. Antimicrobial therapy can be adjusted as necessary when results of
microbiologic testing become available. Invasive diagnostic testing, including
bronchoscopy with bronchoalveolar lavage, may be necessary for specific microbiologic
diagnosis. (See 'Uncomplicated bacterial pneumonia' above and 'Atypical
pneumonia' above and "Community-acquired pneumonia in children: Clinical features and
diagnosis", section on 'Invasive studies'.)

Severe CAP requiring ICU admission Children who are admitted to the intensive care
unit for serious or life-threatening infections require broad-spectrum empiric coverage that
addresses potential beta-lactam resistance and community-associated methicillin-
resistant S. aureus (CA-MRSA). (See 'Indications for intensive care' above.)

A suggested regimen for such children may include (table 2) [43-45]:

Vancomycin 60 mg/kg per day intravenously (IV) in four divided doses up to a


maximum of 4 g/day, and
A third-generation cephalosporin (cefotaxime 150 mg/kg per day IV in four divided
doses up to a maximum of 10 g/day or ceftriaxone 100 mg/kg per day IV in two
divided doses up to a maximum dose of 4 g/day), and
Azithromycin 10 mg/kg once per day IV for two days (maximum
500 mg/day), followed by 5 mg/kg once per day IV (maximum 250 mg/day), and
possibly
Nafcillin or oxacillin 150 mg/kg per day IV in four divided doses; maximum
12 g/day if S. aureus is likely (methicillin-susceptible S. aureus is more rapidly killed
by nafcillin than by vancomycin), and possibly
Antiviral therapy for influenza, if the child is hospitalized during influenza season;
laboratory confirmation of influenza should not delay initiation of antiviral therapy
(see "Seasonal influenza in children: Prevention and treatment with antiviral drugs",
section on 'Antiviral therapy')

This combination is necessary because of reports of treatment failure resulting from


treatment of nonsusceptible S. pneumoniae with beta-lactams,
increasing clindamycin resistance among S. pneumoniae, and concern for MRSA [43].
Virtually all strains of MRSA are susceptible to vancomycin [44]. (See "Methicillin-resistant
Staphylococcus aureus in children: Treatment of invasive infections", section on
'Pneumonia'.)

When treating with vancomycin, renal function and serum trough levels or dosing to
achieve an area under the curve/minimum inhibitory concentration (AUC/MIC) ratio >400
should be monitored in an attempt to assure therapeutic efficacy and limit toxicity. In
adults, vancomycin trough levels between 15 and 20 microgram/mL have been suggested
to improve clinical outcomes for complicated infections due to S. aureus [45-47]. Similar
trough levels may not be needed in children to achieve an AUC/MIC >400 and further
studies are needed to evaluate the clinical effectiveness and safety of these dosing
recommendations in children [47-52].

Linezolid is an oxazolidinone antibiotic with activity against gram-positive cocci, including


beta-lactam-resistant S. pneumoniae and MRSA. Linezolid could be substituted
for vancomycin and nafcillin in the above regimen. The dose for linezolid is 10 mg/kg per
dose (maximum 600 mg); it is administered every eight hours in children younger than 12
years and every 12 hours in children 12 years and older.

Complicated CAP Complicated community-acquired pneumonia (CAP) (eg,


parapneumonic effusion, lung abscess) requires a broader spectrum of antibiotic coverage
if etiologies other than S. pneumoniae are being considered. The expanded spectrum
should include coverage for beta-lactam-resistant isolates and CA-MRSA. Coverage for
anaerobes and gram-negative organisms also may be necessary for children with lung
abscess [53]. Antimicrobial therapy can be adjusted as necessary when results of
microbiologic testing become available. (See "Community-acquired pneumonia in children:
Clinical features and diagnosis", section on 'Complications' and "Management and
prognosis of parapneumonic effusion and empyema in children".)

Complicated CAP requires a prolonged course of antimicrobial therapy, usually initiated


parenterally [24]. Appropriate regimens may include [32]:

Ceftriaxone 100 mg/kg IV in two divided doses up to a maximum dose of


4 g/day, OR cefotaxime 150 mg/kg per day IV in four divided doses up to a maximum
of 10 g/day,PLUS clindamycin 30 to 40 mg/kg per day IV in three or four divided
doses to a maximum of 1 to 2 g/day if S. aureus or anaerobes are a consideration.
Vancomycin 40 to 60 mg/kg per day IV in three or four divided doses up to a
maximum of 4 g/day is an alternative to clindamycin if the patient is allergic to
clindamycin or if clindamycin-resistant S. aureus is prevalent in the community. The
threshold prevalence of clindamycin-resistant MRSA (constitutive plus inducible) for
choosing vancomycin varies from center to center, usually ranging from 10 to 25
percent, trying to balance the benefit of definitive therapy for the patient with the risk
of increasing vancomycin resistance in the community. Additional considerations in
the decision to choose vancomycin include the prevalence of MRSA in the
community, the severity of illness, and the turn-around time for susceptibilities. When
treating with vancomycin, renal function and serum trough levels or dosing to achieve
an AUC/MIC ratio of >400 should be monitored in an attempt to assure therapeutic
efficacy and limit toxicity. In adults, vancomycin trough levels between 15 and
20 microgram/mL have been suggested to improve clinical outcomes for complicated
infections due to S. aureus [45-47]. Similar trough levels may not be needed in
children to achieve an AUC/MIC >400 and further studies are needed to evaluate the
clinical effectiveness and safety of these dosing recommendations in children [47-
52]. (See "Methicillin-resistant Staphylococcus aureus in children: Treatment of
invasive infections", section on 'MRSA infections'.)
Ampicillin-sulbactam 150 to 200 mg/kg per day of the ampicillin component IV in
four divided doses; maximum 12 g/day alone may be effective if a lung abscess is
thought to be secondary to an aspiration event. (See 'Aspiration pneumonia' below.)

The duration of therapy and other considerations in the management of complicated


pneumonia depend upon the type of complication:

Parapneumonic effusion/empyema The treatment of parapneumonic effusion


and empyema is discussed in detail separately. (See "Management and prognosis of
parapneumonic effusion and empyema in children".)
Necrotizing pneumonia Treatment of necrotizing pneumonia requires a
prolonged course of antibiotic therapy. The duration is determined by the clinical
response but is usually a total of four weeks or two weeks after the patient is afebrile
and has improved clinically. Interventional procedures (eg, percutaneous drainage
catheter placement) should be performed cautiously in children with necrotizing
pneumonia; such procedures increase the risk of complications, such as the
development of bronchopleural fistulae [53-56].
Lung abscess Treatment of lung abscess requires a prolonged course of
antibiotic therapy. The duration is determined by the clinical response, but is usually a
total of four weeks or two weeks after the patient is afebrile and has clinical
improvement. The average duration of fever is four to eight days [24]. Eighty to 90
percent of lung abscesses in children resolve with antibiotic therapy alone and
spontaneous drainage through the tracheobronchial tree, provided that bronchial
obstruction is removed [57].
In cases that fail to resolve with antibiotics alone, needle aspiration or percutaneous
catheter drainage may provide diagnostic information and therapeutic benefit without
the increased risk of complications that occurs in children with necrotizing pneumonia
[53,54,58,59]. Percutaneous drainage may be warranted in children with lung
abscess whose condition fails to improve or worsens after 72 hours of antibiotic
therapy [53]. At least three weeks of IV antibiotic therapy should be delivered before
lobectomy is considered for treatment failure [60].
Pneumatocele Most pneumatoceles involute spontaneously [61-63]. However, on
occasion, pneumatoceles result in pneumothorax [64].

Hospital-acquired pneumonia Empiric treatment of hospital-acquired pneumonia


should include coverage for S. aureus, Enterobacteriaceae, Pseudomonas aeruginosa,
and anaerobes. Acceptable broad spectrum regimens usually include an aminoglycoside
(for gram-negative pathogens) and another agent to address gram-positive pathogens and
anaerobes (table 2):

Aminoglycoside (usually gentamicin; amikacin if extended spectrum or Amp C beta-


lactamase producing gram-negative rods are possible etiologies) plus one of the
following:
Piperacillin-tazobactam 300 mg/kg per day IV in four divided doses up to a
maximum of 12 g/day, or
Meropenem 60 mg/kg per day IV in three divided doses, up to a maximum of
6 g/day if extended-spectrum or Amp C beta-lactamase-producing gram-
negative rods are possible etiologies, or
Ceftazidime 125 to 150 mg/kg per day in three divided doses; maximum of
6 g/day, or
Cefepime 150 mg/kg per day in three divided doses; maximum of 4 g/day
Clindamycin 30 to 40 mg/kg per day in three or four divided doses; maximum
3.6 g/day (for patients with type 1 hypersensitivity (table 5) to beta-lactam
antibiotics)

The combination of amikacin and meropenem should be used if extended-spectrum or


Amp C beta-lactamase-producing gram-negative rods are possible etiologies.
The cephalosporin/aminoglycoside combination lacks anaerobic coverage so should NOT
be used when aspiration pneumonia is a possibility. (See 'Aspiration pneumonia' below.)

Vancomycin should be added to the empiric regimen if MRSA is a consideration.

Aspiration pneumonia Empiric antibiotic regimens for community-acquired aspiration


pneumonia must cover oral anaerobes. Appropriate antibiotic regimens for hospitalized
children include [53]:

Ampicillin-sulbactam 150 to 200 mg/kg per day of the ampicillin component IV in


four divided doses; maximum 12 g/day, or
Clindamycin 30 to 40 mg/kg per day IV in three or four divided doses to a maximum
of 1 to 2 g/day if MRSA etiology is suspected.

In neurologically compromised older adolescents prone to aspiration events, empiric


treatment for CAP with a fluoroquinolone like moxifloxacin (400 mg once daily) may be
reasonable. Moxifloxacin has activity against anaerobic bacteria, as well as the usual
treatable causes of CAP (S. pneumoniae, M. pneumoniae, and C. pneumoniae).
Appropriate antibiotic regimens for children with healthcare-associated aspiration who are
known to be colonized with unusual gram-negative pathogens (eg, Klebsiella pneumoniae)
include:

Piperacillin-tazobactam 300 mg/kg per day IV in four divided doses up to a


maximum of 12 g/day, or
Meropenem 60 mg/kg per day IV in three divided doses, up to a maximum of
6 g/day

Vancomycin should be added to the empiric regime if MRSA is a consideration.

Patients with true beta-lactam hypersensitivity (ie, type 1 hypersensitivity reaction) (table
5) can be treated with a combination of clindamycin and an aminoglycoside.

Immunocompromised host Empiric treatment for pneumonia in immunocompromised


hosts also requires broad-spectrum gram-positive and gram-negative coverage, similar to
that required for hospital-acquired pneumonia, with the addition of vancomycin if MRSA is
considered, and possibly trimethoprim-sulfamethoxazole for Pneumocystis
jirovecii (formerly P. carinii). Empiric regimens may need to be modified once results of
cultures and antibiotic susceptibility testing are available. Invasive testing may be required
to obtain a satisfactory specimen in such patients (see "Community-acquired pneumonia in
children: Clinical features and diagnosis", section on 'Invasive studies'). Treatment of CAP
in the immunocompromised host should occur in consultation with an infectious disease
specialist.

An aggressive approach to specific microbial diagnosis is indicated in


immunocompromised hosts with clinically significant pneumonias. For patients with an
endotracheal tube in place, specific microbial diagnosis may involve early flexible
bronchoscopy for bronchoalveolar lavage with viral, fungal, and bacterial cultures.
Although the protected specimen brush technique has been utilized in some settings,
quantitative bacterial cultures are more commonly used to differentiate colonization from
true lower respiratory tract infection. (See "Flexible bronchoscopy in adults: Indications and
contraindications", section on 'Diagnostic indications' and "Clinical presentation and
diagnosis of ventilator-associated pneumonia", section on 'Diagnostic evaluation'.)

SPECIFIC THERAPY Once results of microbiologic tests are available, antimicrobial


therapy can be directed toward the responsible pathogen or pathogens. Specific antibiotic
therapy for bacterial community-acquired pneumonia (CAP) is summarized in the table
(table 6). Specific antimicrobial and/or supportive therapy for the pathogens that commonly
cause CAP in children is discussed in the topic reviews listed below.

S. pneumoniae (see "Pneumococcal pneumonia in children", section on 'Specific


therapy')
M. pneumoniae (see "Mycoplasma pneumoniae infection in children", section on
'Treatment')
C. pneumoniae (see "Pneumonia caused by Chlamydia species in children")
Methicillin-susceptible S. aureus Methicillin-susceptible S. aureus pneumonia may
be treated with oxacillin, nafcillin, or cefazolin [1,4]
Methicillin-resistant S. aureus (MRSA) (see "Methicillin-resistant Staphylococcus
aureus in children: Treatment of invasive infections", section on 'Definitive therapy')
Respiratory syncytial virus (see "Respiratory syncytial virus infection: Treatment")
Influenza (see "Seasonal influenza in children: Prevention and treatment with
antiviral drugs", section on 'Antiviral therapy')
Parainfluenza (see "Parainfluenza viruses in children", section on 'Treatment')
Adenovirus (see "Diagnosis, treatment, and prevention of adenovirus infection",
section on 'Treatment')
Human metapneumovirus (see "Human metapneumovirus infections", section on
'Treatment')

DURATION OF TREATMENT

Parenteral therapy There are few data to guide decisions about the duration of
parenteral therapy for community-acquired pneumonia (CAP) [2]. It is common to switch to
oral therapy in patients who have received parenteral antibiotics when the patient has
become afebrile for 24 to 48 hours and is not having emesis [65].

Total duration There are few randomized controlled trials to guide decisions about the
appropriate duration of antimicrobial therapy for radiographically confirmed childhood
pneumonia [2]. Current practice assigns duration of therapy according to the host,
causative agent, and severity.

Uncomplicated cases The usual duration of combined parenteral and oral therapy for
uncomplicated pneumonia is 7 to 10 days [1,2]. Some authorities suggest continuing oral
therapy at least one week beyond resolution of fever; others suggest treating until the
erythrocyte sedimentation rate falls below 20 mm/hour. Some data from trials in adults
suggest that a shorter course may be equivalent to a 7- to 10-day course, but additional
controlled studies are necessary before this practice can be recommended routinely for
children [53,66-68].

Complicated cases Treatment of complications, such as necrotizing pneumonia and


lung abscess, requires a prolonged course of antibiotic therapy, usually initiated
parenterally. The duration is determined by the clinical response, but usually is either a
total of four weeks or a total of two weeks after the patient is afebrile and has improved
clinically. (See 'Complicated CAP' above.)
RESPONSE TO THERAPY The following clinical parameters can be monitored to
assess response to treatment [1,2]:

Temperature
Respiratory rate
Heart rate
Oxygen saturation (SpO2)
Work of breathing (eg, retractions, nasal flaring, grunting)
Chest examination (extent of abnormal or absent breath sounds; extent of dullness
to percussion)
Mental status
Ability to maintain oral intake and hydration

The frequency of monitoring depends upon the severity of illness. In patients who are
receiving oxygen supplementation, oxygen saturation should be evaluated regularly.
Evaluation for hypercarbia may be necessary in children with severe respiratory distress,
as oxygenation may be preserved.

The respiratory status of children with community-acquired pneumonia (CAP) who are
appropriately treated should improve within 48 to 72 hours [1]. However, fevers may
persist for several days after initiation of appropriate therapy [53].

Treatment failure In children who fail to improve as anticipated, the following


possibilities must be considered [1,2,69,70]:

Alternative or coincident diagnoses (eg, foreign body aspiration) (see "Community-


acquired pneumonia in children: Clinical features and diagnosis", section on
'Differential diagnosis')
Ineffective antibiotic coverage (lack of coverage for the actual etiology or resistant
organism)
Development of complications (see "Community-acquired pneumonia in children:
Clinical features and diagnosis", section on 'Complications')
Underlying immunodeficiency condition

The history should be reviewed with special attention to the possibility of foreign body
aspiration and geographic or environmental exposures associated with pathogens not
treated by the empiric regimen (table 7).

Changes in laboratory parameters (eg, peripheral white blood cell count, inflammatory
markers [if obtained initially]) may provide information about disease progression. Repeat
radiographs or additional imaging studies can help to assess the degree of parenchymal
involvement and evaluate for complications or anatomic abnormalities [1].
(See "Community-acquired pneumonia in children: Clinical features and diagnosis",
section on 'Complications' and "Pneumonia in children: Epidemiology, pathogenesis, and
etiology", section on 'Etiologic agents'.)

Depending upon the severity of illness, more aggressive attempts may need to be made to
establish a microbiologic diagnosis (eg, induced sputum [71], bronchoscopy with
bronchoalveolar lavage, percutaneous needle aspiration, or lung biopsy). In children with
lung abscess whose condition fails to improve or worsens after 72 hours of antibiotic
therapy, needle aspiration or percutaneous catheter drainage may provide diagnostic
information and therapeutic benefit [53,54,58,59]. (See "Community-acquired pneumonia
in children: Clinical features and diagnosis", section on 'Invasive studies'.)

DISCHARGE CRITERIA Discharge criteria for children who have been admitted to the
hospital with community-acquired pneumonia (CAP) have not been standardized, but
typically include [1,53]:

Improvement of vital signs


Ability to maintain adequate fluid and nutrition orally
Ability to maintain oxygen saturation 90 percent in room air
Improvement in respiratory status
Overall clinical improvement including level of activity, appetite, and decreased fever
for at least 12 to 24 hours
Stable and/or baseline mental status
Parents' ability to administer and child's ability to comply with home antibiotic
regimen
Safe and compliant home environment

Outpatient parenteral antibiotic therapy Outpatient parenteral antimicrobial therapy


(OPAT) is an option for selected patients who require prolonged treatment (usually for
complicated CAP that for some reason cannot be treated with an oral antibiotic) and have
stabilized clinically [53,72,73]. Eligibility for OPAT requires a suitable home environment
and a pharmacologic agent with a reasonable dosing schedule [74]. Decisions regarding
OPAT should involve the caregivers, an infectious disease specialist (or clinician
knowledgeable about the use of antimicrobial agents in OPAT), a hospital pharmacist, and
the primary care provider. The services of a visiting nurse may be required for home visits,
education and observation of caregiver administration, and/or obtaining blood samples for
therapeutic monitoring.

FOLLOW-UP

Clinical course Children with pneumonia should be seen by their primary care provider
soon after discharge to ensure that clinical improvement continues and antibiotic therapy is
being taken as prescribed [53]. Decisions regarding the timing of clinical follow-up should
involve the child's primary care provider and the clinical status of the child at the time of
discharge.
Children who are appropriately treated for pneumonia should gradually improve with time.
Cough may persist for as long as three to four months after viral pneumonia or pertussis.
Children who are recovering from typical or atypical bacterial pneumonia may continue to
cough for several weeks and have moderate dyspnea on exertion for two to three months
[75]. Symptomatic treatment of cough is discussed separately. (See "The common cold in
children: Management and prevention", section on 'Cough'.)

Radiographs Follow-up radiographs are not necessary in asymptomatic children with


uncomplicated community-acquired pneumonia (CAP). However, in children with
complicated CAP or CAP that required intervention, follow-up radiographs help to ensure
resolution [2,76]. Follow-up radiographs also may be helpful in children with recurrent
pneumonia, persistent symptoms, severe atelectasis, unusually located infiltrates, or round
pneumonia (ie, pulmonary consolidation that appears to be spherical) [2,53,77]. Conditions
that must be considered if a round pneumonia fails to resolve on follow-up imaging include
congenital lung sequestration, metastatic Wilms tumor, cavitary necrosis, pleural
pseudocyst, and primary lung carcinoma [77-81]. When follow-up radiographs are
indicated, they should be obtained two to three weeks after hospital discharge [53,82].

Several studies have evaluated the utility of follow-up radiographs in cohorts of children
with acute radiologically proven CAP [83-88]. Three of the studies included clinical as well
as radiologic follow-up at three to seven weeks after initial diagnosis [83-86]. In each of
these studies, follow-up radiographs were normal or improved in asymptomatic children.
Residual findings, even when present, did not result in additional therapy.

PROGNOSIS Most otherwise healthy children with pneumonia recover without


sequelae, even if the pneumonia is complicated [53,55,56,89]. In a multicenter cohort
study, approximately 3 percent of 82,566 children hospitalized with pneumonia were
readmitted with pneumonia within 30 days of discharge; 8 percent were readmitted for any
reason. Readmission was more common among children younger than one year and
children with chronic medical conditions [90].

Although some data suggest that nearly one-half of children who are hospitalized for viral
pneumonia have symptoms of asthma five years after hospitalization, it is not clear
whether this is related to unrecognized asthma at the time of presentation with pneumonia
or a tendency to develop asthma after community-acquired viral pneumonia [91,92].

The overall pneumonia mortality rate in developed countries is <1 per 1000 per year
[25,93]. Pneumococcal pneumonia case fatality rates (not adjusted for comorbid
conditions) for children in the United States were estimated to be 4 percent in children
younger than two years and 2 percent in children 2 to 17 years before the introduction of
pneumococcal conjugate vaccines [94].

The introduction of pneumococcal conjugate vaccines has resulted in a dramatic reduction


(37 to 80 percent) in invasive disease and mortality rates in the countries in which they
have been introduced [95]. However, pneumococcal pneumonia mortality rates have not
been specifically examined. Data from the United States Pediatric Multicenter
Pneumococcal Surveillance Study Group demonstrated overall pneumococcal mortality
rates of 1 percent after the introduction of PCV7 (during 2006 to 2009) and 0 percent after
the introduction of PCV13 (during 2011 to 2014) [96] In a study from eastern Gambia,
introduction of a nine-valent pneumococcal conjugate vaccine resulted in reduced all-
cause mortality (25.2 versus 30.1 per 1000 child-years, a 16 percent reduction) [97].
(See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children", section
on 'Efficacy and effectiveness'.)

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines


from selected countries and regions around the world are provided separately.
(See "Society guideline links: Community-acquired pneumonia in children".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Pneumonia in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

The decision to hospitalize a child with community-acquired pneumonia (CAP) must


be individualized and is based upon age, underlying medical problems, and severity
of illness (table 1). (See 'Indications' above.)
CAP can be caused by a variety of microbial agents requiring a variety of infection-
control measures. (See 'Infection control' above.)
Supportive care for children hospitalized with pneumonia includes provision of
adequate respiratory support, hydration, antipyresis, and analgesia. (See 'Supportive
care' above.)
Children with CAP who are hospitalized are treated empirically until information from
the microbiologic evaluation is available to direct therapy toward a specific pathogen.
Decisions regarding empiric antimicrobial therapy for CAP in children are usually
based upon age unless there are other overriding epidemiologic or clinical factors to
suggest a specific etiologic agent (table 2). (See 'Overview' above and "Pneumonia in
children: Epidemiology, pathogenesis, and etiology", section on 'Etiologic agents'.)
We recommend that empiric antibiotic therapy for presumed bacterial pneumonia in
hospitalized children include coverage for Streptococcus pneumoniae (table 2)
(Grade 1B). (See 'Uncomplicated bacterial pneumonia' above.)
Extended empiric coverage may be indicated for children with complicated or severe
pneumonia, particularly those who require admission to an intensive care unit (table
2). (See 'Complicated CAP' above and 'Severe CAP requiring ICU admission' above.)
When results of microbiologic tests are available, antibiotic therapy can be directed
toward the specific pathogen recovered (table 6). (See 'Specific therapy' above.)
Oral therapy typically is initiated when the patient has been afebrile for 24 to 48
hours and can tolerate oral intake. The total duration of antibiotic therapy is usually 7
to 10 days for uncomplicated CAP and up to four weeks in complicated CAP.
(See 'Duration of treatment' above.)
The respiratory status of children receiving appropriate therapy for CAP should
improve within 48 to 72 hours. Children who fail to improve as anticipated may be
receiving inadequate antibiotic therapy, have developed complications, or have an
alternative or coincident diagnosis. (See 'Treatment failure' above.)
Children recovering from CAP may continue to have cough for several weeks to four
months, depending upon the etiology. Those recovering from typical or atypical
bacterial pneumonia may have moderate dyspnea on exertion for two to three
months. (See 'Clinical course' above.)
Follow-up radiographs are not necessary in asymptomatic children with
uncomplicated CAP. However, in children with complicated CAP or CAP that required
intervention, follow-up radiographs help to ensure resolution. Follow-up radiographs
two to three weeks after completion of therapy may be helpful in children with
recurrent pneumonia, persistent symptoms, severe atelectasis, round pneumonia, or
unusually located infiltrates. (See 'Radiographs' above.)
Most otherwise healthy children who develop pneumonia recover without any long-
term sequelae. (See 'Prognosis' above.)

neumonia in children: Epidemiology, pathogenesis, and etiology

Author:
William J Barson, MD
Section Editor:
Sheldon L Kaplan, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jan 17, 2017.

INTRODUCTION Childhood pneumonia is an important cause of morbidity in the


developed world, and morbidity and mortality in the developing world. The epidemiology,
microbiology, and pathogenesis of pneumonia in children will be reviewed here. The
clinical features, diagnosis, and treatment of pneumonia in children are discussed
separately, as is pneumonia in neonates (<28 days of age). (See "Community-acquired
pneumonia in children: Clinical features and diagnosis" and "Community-acquired
pneumonia in children: Outpatient treatment" and "Pneumonia in children: Inpatient
treatment" and "Neonatal pneumonia".)

TERMINOLOGY The terms pneumonia and pneumonitis strictly represent any


inflammatory condition involving the lungs, which include the visceral pleura, connective
tissue, airways, alveoli, and vascular structures. Lower respiratory tract infection (LRTI) is
frequently used interchangeably to include bronchitis, bronchiolitis, and pneumonia, or any
combination of the three. For the purposes of this review, pneumonia will be defined as a
condition typically associated with fever, respiratory symptoms, and evidence of
parenchymal involvement, either by physical examination or the presence of infiltrates on
chest radiography. Bronchiolitis is discussed separately. (See "Bronchiolitis in infants and
children: Clinical features and diagnosis", section on 'Clinical features'.)

EPIDEMIOLOGY

Incidence The World Health Organization (WHO) estimates there are 156 million cases
of pneumonia each year in children younger than five years, with as many as 20 million
cases severe enough to require hospital admission [1]. In the developed world, the annual
incidence of pneumonia is estimated to be 33 per 10,000 in children younger than five
years and 14.5 per 10,000 in children 0 to 16 years [2].

Approximately one-half of children younger than five years of age with community-
acquired pneumonia (CAP) require hospitalization [3]. Hospitalization rates for pneumonia
(all causes) among children younger than two years in the United States decreased after
introduction of the pneumococcal conjugate vaccine to the routine childhood immunization
schedule in 2000 (from 12 to 14 per 1000 population to 8 to 10 per 1000 population)
(figure 1) [4].

Mortality The mortality rate in developed countries is low (<1 per 1000 per year) [5,6].
In developing countries, respiratory tract infections are not only more prevalent but more
severe, accounting for more than 2 million deaths annually; pneumonia is the number one
killer of children in these societies [1,7].

Seasonality Although both viral and bacterial pneumonia occur throughout the year,
they are more prevalent during the colder months, presumably because direct
transmission of infected droplets is enhanced by indoor crowding. For reasons that are
unknown, different viruses cause peaks of infection at different times during the respiratory
virus season and these peaks seldom occur simultaneously [8]. In tropical regions, peaks
of infection follow no common pattern and can occur during either the wet or dry seasons.

Risk factors Lower socioeconomic groups have a higher prevalence of LRTIs, which
correlates best with family size, a reflection of environmental crowding. School-age
children often introduce respiratory viral agents into households, resulting in secondary
infections in their parents and siblings [8].

Underlying cardiopulmonary disorders and other medical conditions predispose to


pneumonia and contribute to increasing severity. These include [5,9]:

Congenital heart disease


Bronchopulmonary dysplasia
Cystic fibrosis
Asthma
Sickle cell disease
Neuromuscular disorders, especially those associated with a depressed
consciousness
Some gastrointestinal disorders (eg, gastroesophageal reflux, tracheoesophageal
fistula)
Congenital and acquired immunodeficiency disorders

Cigarette smoke compromises natural pulmonary defense mechanisms by disrupting both


mucociliary function and macrophage activity [10]. Exposure to cigarette smoke, especially
if the mother smokes, increases the risk for pneumonia in infants younger than one year of
age. (See "Secondhand smoke exposure: Effects in children".)

The use of cigarettes, alcohol, and other substances of abuse in adolescents may
increase the risk of pneumonia by increasing the risk of aspiration through impairment of
the cough and epiglottic reflexes. In addition, the use of alcohol has been associated with
increased colonization of the oropharynx with aerobic gram-negative bacilli [11].

Effect of vaccines Immunization with the Haemophilus influenzae type b (Hib) and
pneumococcal conjugate vaccines protects children from invasive disease caused by
these organisms. Hib was once a common cause of pneumonia in young children in the
United States. However, it has been virtually eliminated as a result of routine immunization
with Hib conjugate vaccines. (See "Prevention of Haemophilus influenzae type b infection",
section on 'Efficacy/effectiveness'.)

The universal immunization of infants in the United States with the 7-valent pneumococcal
conjugate vaccine has effectively decreased the incidence of pneumonia requiring
hospitalization and other invasive Streptococcus pneumoniae infections in children
younger than two years (figure 1) [12-15]. Rates of ambulatory visits for pneumonia in
children younger than two years also declined after the introduction of pneumococcal
conjugate vaccine [16], but the rates for children aged 1 to 18 years remained stable [17].
(See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children", section
on 'Pneumonia'.)

It is anticipated that the 13-valent pneumococcal conjugate vaccine that replaced the 7-
valent pneumococcal conjugate vaccine in 2010, and affords additional coverage against
serotypes 1, 3, 5, 6A, 7F, and 19A, will further decrease the incidence of pneumonia
requiring hospitalization because these serotypes are responsible for the majority of
pneumococcal pneumonia cases among children worldwide [18,19]. Early data from the
United States Pediatric Multicenter Pneumococcal Surveillance Group demonstrate a 53
percent reduction in cases of pneumonia compared with the average number of cases for
2007 to 2009 [20]. (See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines
in children", section on '13-valent vaccine'.)

Pneumococcal vaccination also protects against viral pneumonia. This was shown in a
double-blind, randomized, placebo-controlled trial in which full immunization with a nine-
valent pneumococcal conjugate vaccine was associated with a 31 percent reduction (95%
CI 15-43) in the incidence of pneumonia associated with any of seven respiratory viruses
(influenza A/B, parainfluenza types 1 to 3, respiratory syncytial virus [RSV], adenovirus) in
hospitalized children [21]. This observation suggests that the pneumonias associated with
these viruses in hospitalized children are often because of concurrent pneumococcal
infection.

PATHOGENESIS Pneumonia occurs because of an impairment of host defenses,


invasion by a virulent organism, and/or invasion by an overwhelming inoculum.

In the typical scenario, pneumonia follows an upper respiratory tract illness that permits
invasion of the lower respiratory tract by bacteria, viruses, or other pathogens that trigger
the immune response and produce inflammation [3,22]. The lower respiratory tract air
spaces fill with white blood cells (WBC), fluid, and cellular debris. This process reduces
lung compliance, increases resistance, obstructs smaller airways, and may result in
collapse of distal air spaces, air trapping, and altered ventilation-perfusion relationships [3].
Severe infection is associated with necrosis of bronchial or bronchiolar epithelium
[23], and/or pulmonary parenchyma [24].

Acquisition The agents that cause lower respiratory tract infection (LRTI) are most
often transmitted by droplet spread resulting from close contact with a source case.
Contact with contaminated fomites also may be important in the acquisition of viral agents,
especially respiratory syncytial virus (RSV).

Most typical bacterial pneumonias are the result of initial colonization of the nasopharynx
followed by aspiration or inhalation of organisms. Invasive disease most commonly occurs
upon acquisition of a new serotype of the organism with which the patient has not had
previous experience, typically after an incubation period of one to three days. Occasionally,
a primary bacteremia may precede the pneumonia. Atypical bacterial pathogens attach to
respiratory epithelial membranes through which they enter cells for replication.

The viral agents that cause pneumonia proliferate and spread by contiguity to involve
lower and more distal portions of the respiratory tract.

Normal host defense The pulmonary host defense system is complex and includes
anatomic and mechanical barriers, humoral immunity, phagocytic activity, and cell-
mediated immunity [25,26], as discussed below, with a focus on bacterial infection. The
host response to respiratory viral infection is beyond the scope of this review; more
information can be obtained from reference [27].

Anatomic and mechanical barriers Anatomic and mechanical barriers in the upper
airway form an important part of the host defense. Particles greater than 10 microns
are efficiently filtered by the hairs in the anterior nares or impact onto mucosal
surfaces. The nasal mucosa contains ciliated epithelium and mucus-producing cells.
The cilia beat synchronously, clearing the entrapped organisms through the
nasopharynx via expulsion or swallowing. In the oropharynx, salivary flow, sloughing
of epithelial cells, local production of complement and immunoglobulin A (IgA), and
bacterial interference from the resident flora serve as important factors in local host
defense.
An intact epiglottic reflex helps to prevent aspiration of infected secretions, and the
cough reflex helps to expel materials that may be aspirated. The sharp angles at
which the central airways branch cause 5 to 10 micron particles to impact on mucosal
surfaces, where they are entrapped in endobronchial mucus. Once entrapped, the
ciliary system moves the particles upward out of the airways into the throat, where
they are normally swallowed.
Humoral immunity Secretory IgA is the major immunoglobulin produced in the
upper airways and accounts for 10 percent of the total protein concentration of nasal
secretions. Although it is not a very good opsonizing agent, it does possess
antibacterial and antiviral activity. IgG and IgM enter the airways and alveolar spaces
predominantly via transudation from the blood and act to opsonize bacteria, activate
complement, and neutralize toxin. Immunoglobulins, surfactant, fibronectin, and
complement act as effective opsonins to help eliminate microorganisms (0.5 to 1
micron particles) that reach the terminal airways and alveoli. Free fatty acids,
lysozyme, and iron-binding proteins also are present and may be microbicidal.
Phagocytic cells There are two populations of phagocytic cells in the lung:
polymorphonuclear leukocytes (PMNs) from the blood and macrophages. There are
several distinct populations of macrophages, which vary in their location and function:
The alveolar macrophage is located in the alveolar fluid and is the first
phagocyte encountered by inert particles and potential pathogens entering the
lung. If this cell is overwhelmed, it has the capacity to become a mediator of
inflammation and produce cytokines that recruit neutrophils.
Interstitial macrophages are located in the lung connective tissue and serve
both as phagocytic cells and antigen-processing cells.
The intravascular macrophage is located in capillary endothelial cells and
phagocytizes and removes foreign material entering the lungs via the
bloodstream.
Cell-mediated immunity Cell-mediated immunity is especially important against
certain pathogens, including viruses and intracellular microorganisms that can survive
within pulmonary macrophages. Although relatively few in number (5 to 10 percent of
the total lung parenchyma cell population), lymphocytes play three critical roles: the
production of antibody, cytotoxic activity, and the production of cytokines.

Patterns of pneumonia There are five patterns of bacterial pneumonia [22]:

Lobar pneumonia Involvement of a single lobe or segment of a lobe. This is the


classic pattern of S. pneumoniae pneumonia.
Bronchopneumonia Primary involvement of airways and surrounding interstitium.
This pattern is sometimes seen in Streptococcus pyogenes and Staphylococcus
aureus pneumonia.
Necrotizing pneumonia (associated with aspiration pneumonia and pneumonia
resulting from S. pneumoniae, S. pyogenes, and S. aureus) (image 1).
Caseating granuloma (as in tuberculous pneumonia).
Interstitial and peribronchiolar with secondary parenchymal infiltration This pattern
typically occurs when a severe viral pneumonia is complicated by bacterial
pneumonia.

There are two major patterns of viral pneumonia [22]:

Interstitial pneumonitis (image 2)


Parenchymal infection with viral inclusions

Examination findings The examination findings vary depending on the site of infection
as follows [3]:

Inspiratory crackles, also called rales and crepitations [28], are more common in
lobar pneumonia and bronchiolitis/pneumonia
Decreased breath sounds may be noted in areas of consolidation
Coarse, low-pitched continuous breath sounds (rhonchi) are more common in
bronchopneumonia
Expiratory wheezes, high-pitched breath sounds, are caused by oscillation of air
through a narrowed airway; they are more common in bronchiolitis and interstitial
pneumonitis
ETIOLOGIC AGENTS A large number of microorganisms have been implicated as
etiologic agents of pneumonia in children (table 1A-B). The agents commonly responsible
vary according to the age of the child and the setting in which the infection is acquired.

Community-acquired pneumonia

Overview The true prevalence of the various etiologic agents in community-acquired


pneumonia (CAP) in children is uncertain [29]. Studies investigating the etiology of
childhood pneumonia have been performed in populations of various ages, in various
settings, and using a variety of microbiologic techniques [6,30-41]. Because direct culture
of infected lung tissue requires invasive techniques, published studies primarily use
laboratory tests that provide indirect evidence of etiology. These indirect methods include
nasopharyngeal culture, blood culture, polymerase chain reaction, and serology. In
addition to the use of indirect methods, interpretation of the results is hampered by the
failure to identify an organism in 15 to 35 percent of cases and the frequency of mixed
infections (in 23 to 33 percent of cases) [2,6]. Most of these studies were performed before
the licensure of the pneumococcal conjugate vaccine [42].

Despite these problems, systematic reviews have identified some consistent trends and
conclusions regarding the etiology of CAP in children, which are listed below [2,29]:

S. pneumoniae is the most common bacterial cause of pneumonia in children [9,43]


Viruses alone account for 14 to 35 percent of cases, and up to 50 percent of cases
in young children
Viruses are more commonly identified in children younger than five years
In children older than five years, Mycoplasma
pneumoniae and Chlamydophilapneumoniae are more common [6,44,45]

In some areas in which community-associated methicillin-resistant Staphylococcus


aureus (CA-MRSA) is a major issue, CA-MRSA is becoming an important cause of CAP
complicated by empyema and necrosis [46,47]. When associated with influenza, MRSA
CAP can be particularly severe [48,49]. (See "Epidemiology; clinical presentation; and
evaluation of parapneumonic effusion and empyema in children" and "Methicillin-resistant
Staphylococcus aureus infections in children: Epidemiology and clinical spectrum", section
on 'Epidemiology and risk factors'.)

In neonates The etiology of pneumonia in neonates (infants <28 days of age) is


discussed separately. (See "Neonatal pneumonia", section on 'Microbiology'.)

In infants As described below, viruses are the most common etiology of CAP in
children younger than five years, including infants. However, infants younger than one year
also may develop "afebrile pneumonia of infancy." Afebrile pneumonia of infancy is a
syndrome generally seen between two weeks and three to four months of life. It is
classically caused by Chlamydia trachomatis, but other agents, such as cytomegalovirus
(CMV), Mycoplasma hominis, and Ureaplasma urealyticum, also are implicated.
(See "Chlamydia trachomatis infections in the newborn", section on 'Pneumonia'.)

Infants with severe Bordetella pertussis infection also may develop pneumonia.
(See "Pertussis infection in infants and children: Clinical features and diagnosis", section
on 'Complications'.)

In children <5 years

Viruses Viruses are the most common etiology of CAP in older infants and children
younger than five years of age [2,6,29]. However, bacterial pathogens, including S.
pneumoniae, S. aureus, and S. pyogenes, also are important because they are
associated with increased morbidity and mortality [47,48,50].
Respiratory syncytial virus (RSV), a member of the Paramyxoviridae virus family, is
the most common viral pathogen responsible for pneumonia in children younger than
five years [6,36,51]. RSV pneumonia frequently represents an extension of
bronchiolitis. (See "Bronchiolitis in infants and children: Clinical features and
diagnosis", section on 'Clinical features' and "Respiratory syncytial virus infection:
Clinical features and diagnosis", section on 'Clinical manifestations'.)
Other viral causes of pneumonia in children younger than five years include [6]:
Influenza A and B viruses.
Parainfluenza viruses, usually type 3. (See "Parainfluenza viruses in children",
section on 'Clinical presentation'.)
A number of adenovirus serotypes (1, 2, 3, 4, 5, 7, 14, 21, and 35) have been
reported to cause pneumonia; serotypes 3, 7, and 21 have been associated with
severe and complicated pneumonia [52]. (See "Epidemiology and clinical
manifestations of adenovirus infection", section on 'Clinical presentation'.)
Human metapneumovirus, identified in 2001, is a common cause of lower
respiratory tract infections in children; most children have been infected by five
years of age. (See "Human metapneumovirus infections".)
Rhinovirus has been implicated as a cause of pneumonia using PCR assays
[53], but its etiologic role is questioned [51,54,55].
Coronaviruses, including the severe acute respiratory syndrome (SARS), the
Middle East respiratory syndrome (MERS), and the New Haven coronaviruses,
also cause respiratory tract infections in children younger than five years [56,57].
However, their clinical impact has yet to be fully determined [51,58].
(See "Coronaviruses", section on 'Respiratory' and "Severe acute respiratory
syndrome (SARS)", section on 'Clinical manifestations' and "Middle East
respiratory syndrome coronavirus: Clinical manifestations and diagnosis",
section on 'Clinical manifestations'.)
Human bocavirus and human parechovirus types 1, 2, and 3 also have been
implicated as a cause of lower respiratory tract infections in children [59-61].
Enterovirus D68 emerged as a significant pathogen of lower respiratory tract
disease among United States children in 2014 [62]. (See "Epidemiology,
pathogenesis, treatment, and prevention of enterovirus and parechovirus
infections", section on 'Serotypes and disease' and "Clinical manifestations and
diagnosis of enterovirus and parechovirus infections", section on 'Respiratory
disease'.)
Bacteria Important bacterial causes of pneumonia in preschool children include S.
pneumoniae, H. influenzae type b, nontypeable H. influenzae, Moraxella
catarrhalis, S. aureus, S. pyogenes, and atypical bacteria.
S. pneumoniae is the single most common bacterial pathogen causing
pneumonia in all patients beyond the first few weeks of life [9,43].
(See "Pneumococcal pneumonia in children", section on 'Epidemiology'.)
H. influenzae type b is a rare cause of pneumonia in countries with universal
childhood immunization.
S. aureus (particularly community-associated MRSA, CA-MRSA) and S.
pyogenes are becoming increasingly frequent causes of CAP, particularly those
complicated by necrosis and empyema [47,63]. In addition, these organisms
occasionally cause pneumonia following influenza and chickenpox, respectively
[48,49]. (See "Clinical features of varicella-zoster virus infection: Chickenpox".)
The prevalence of M. pneumoniae and C. pneumoniae may be increasing in
preschool children with CAP [29,64]. (See "Pneumonia caused by Chlamydia
species in children" and "Mycoplasma pneumoniae infection in children", section
on 'Epidemiology'.)

In children 5 years

S. pneumoniae is the most common typical bacterial cause of pneumonia in children


older than five years (see "Pneumococcal pneumonia in children", section on
'Epidemiology')
M. pneumoniae is more common among children 5 years than among younger
children (see "Mycoplasma pneumoniae infection in children", section on
'Epidemiology')
C. pneumoniae also is emerging as a frequent cause of pneumonia in older children
and young adults (see "Pneumonia caused by Chlamydia species in children")

Aspiration pneumonia When there is a predisposition to aspiration, pneumonia may


be caused by anaerobic oral flora, including:

Anaerobic streptococci (eg, Peptostreptococcus)


Fusobacterium spp
Bacteroides spp
Prevotella melaninogenica
Risk factors for aspiration include a history of seizure, anesthesia, or other episode of
reduced level of consciousness, neurologic disease, dysphagia, gastroesophageal reflux,
alcohol or substance abuse, use of a nasogastric tube, or foreign body aspiration.

Healthcare-associated pneumonia Healthcare-associated bacterial pneumonia is


usually caused by gram-negative bacilli or S. aureus. Healthcare-associated pneumonia
frequently occurs in intensive care units where mechanical ventilation, indwelling
catheters, and administration of broad-spectrum antibiotics are common. (See "Pneumonia
in children: Inpatient treatment", section on 'Hospital-acquired pneumonia'.)

In addition, during the winter respiratory viral season, all patients in a medical care
environment are at risk for healthcare-associated pneumonia caused by RSV,
parainfluenza, and influenza viruses. (See "Seasonal influenza in children: Clinical
features and diagnosis" and "Parainfluenza viruses in children", section on 'Clinical
presentation' and "Respiratory syncytial virus infection: Clinical features and diagnosis",
section on 'Transmission'.)

Special populations

Immunocompromised The causes of pneumonia in immunocompromised hosts


include all of the pathogens mentioned above, as well as a variety of other organisms, as
discussed below.

Gram-negative bacilli and S. aureus are common etiologies in neutropenic patients or in


those with white blood cell (WBC) defects. Clinically significant legionellosis usually is
seen only in immunocompromised hosts with an exposure to an aquatic reservoir
of Legionella pneumophila, such as a river, lake, air-conditioning cooling tower, or water
distribution systems [65,66]. However, seroepidemiologic studies suggest that subclinical
or minor infections occur in children [67,68]. (See "Epidemiology and pathogenesis of
Legionella infection".)

Opportunistic fungi, such as Aspergillus spp and Fusarium spp, also are a concern in
neutropenic patients and in those receiving immunosuppressive therapies that impair the
cell-mediated response. One of the more common pneumonia pathogens diagnosed in
HIV-infected patients is Pneumocystis jirovecii, which was formerly called Pneumocystis
carinii [69]. (See "Epidemiology and clinical manifestations of invasive
aspergillosis" and "Mycology, pathogenesis, and epidemiology of Fusarium
infection" and "Pediatric HIV infection: Classification, clinical manifestations, and
outcome", section on 'Pneumocystis jirovecii pneumonia'.)

Viral causes of pneumonia, which may be life-threatening in the immunocompromised


host, including the post-solid organ and stem cell transplant populations include:
Common community-acquired viral agents such as RSV, adenovirus, influenza,
parainfluenza, rhinovirus, and human metapneumovirus [70,71] (see appropriate topic
reviews)
Rubeola (Hecht giant-cell pneumonia) (see "Measles: Clinical manifestations,
diagnosis, treatment, and prevention", section on 'Immunocompromised patients')
Varicella-zoster virus (VZV) (see "Clinical features of varicella-zoster virus infection:
Chickenpox", section on 'Pneumonia')
CMV (see "Acquired cytomegalovirus infection in children", section on 'CMV
infection in immunocompromised hosts')
Epstein-Barr virus (EBV), which may be the trigger for lymphocytic interstitial
pneumonitis, an indolent but progressive process that occurs in children infected with
HIV (see "Clinical manifestations and treatment of Epstein-Barr virus
infection" and "Lymphocytic interstitial pneumonia in children", section on
'Pathogenesis')

Cystic fibrosis Young children with cystic fibrosis frequently are infected with S.
aureus, P. aeruginosa, and H. influenzae (mostly nontypeable strains). Later in the course
of the disease, multiple drug-resistant gram-negative organisms, such as Burkholderia
cepacia, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans, can be
recovered. Aspergillus spp and nontuberculous mycobacteria also may cause disease in
this population. Cystic fibrosis lung disease is discussed in detail separately. (See "Cystic
fibrosis: Clinical manifestations of pulmonary disease" and "Cystic fibrosis: Overview of the
treatment of lung disease" and "Cystic fibrosis: Antibiotic therapy for lung disease".)

Sickle cell anemia The prevalence of pneumonia is increased in children with sickle
cell anemia [72]. Atypical bacterial pathogens appear to be most frequent and are more
commonly associated with the acute chest syndrome. Other bacterial causes of
pneumonia in children with sickle cell anemia include S. pneumoniae, S. aureus, and H.
influenzae [9]. (See "The acute chest syndrome in children and adolescents with sickle cell
disease", section on 'Infection'.)

Environmental considerations

Geography Residence in or travel to specific geographic areas should suggest


endemic pathogens:

Tuberculosis is most common in immigrants from countries with a high prevalence of


infection (eg, countries throughout Asia, Africa, Latin America, and Eastern Europe)
(figure 2). (See "Epidemiology of tuberculosis".)
Measles pneumonia is common in the developing world. (See "Measles: Clinical
manifestations, diagnosis, treatment, and prevention".)
Coccidioides immitis is endemic to the southwestern United States, northern
Mexico, and parts of Central and South America. (See "Primary coccidioidal
infection".)
Blastomyces dermatitidis, causing blastomycosis, is endemic in the southeastern
and central states and the midwestern states bordering the Great Lakes.
(See "Mycology, pathogenesis, and epidemiology of blastomycosis" and "Treatment
of blastomycosis".)
Histoplasma capsulatum is endemic in the Ohio, Mississippi, and Missouri River
valleys in the United States; in 2013 it was reported for the first time in Montana [73].
It also occurs in Canada, Central America, eastern and southern Europe, parts of
Africa, eastern Asia, and Australia. Activities potentially leading to exposure to bird
droppings and bat guano may be suggestive. These include gardening, construction,
cleaning of barns and outbuildings, and spelunking. (See "Pathogenesis and clinical
features of pulmonary histoplasmosis" and "Diagnosis and treatment of pulmonary
histoplasmosis".)
In the United States, hantavirus cardiopulmonary syndrome (acute febrile illness
associated with respiratory failure, shock, and high mortality) occurs predominantly
west of the Mississippi River (in the "four corners" region where the borders of
Colorado, New Mexico, Arizona, and Utah meet) after environmental exposure to
infected deer mouse (Peromyscus maniculatus) saliva, urine, or feces. Activities
associated with exposure include cleaning of barns and outbuildings, trapping
rodents, animal herding, and farming with hand tools. (See "Epidemiology and
diagnosis of hantavirus infections" and "Hantavirus cardiopulmonary syndrome".)

Animal exposures Histoplasmosis is associated with exposure to bird droppings and


bat guano, and hantavirus infection is associated with exposure to an infected deer
mouse. Other causes of pneumonia that are associated with animal exposure include:

Chlamydophila psittaci (psittacosis), which is transmitted to man predominantly from


domestic and wild birds (see "Psittacosis")
Coxiella burnetii (Q fever), which is associated with exposure to parturient sheep,
goats, cattle, and cats (or exposure to dust/soil contaminated by these animals)
(see "Microbiology and epidemiology of Q fever" and "Clinical manifestations and
diagnosis of Q fever")

Other exposures Exposure to individuals at high risk for tuberculosis is a risk factor for
the development of tuberculosis in children. High-risk individuals include the homeless,
recent immigrants from endemic regions (figure 2), incarcerated individuals, and HIV-
infected patients. (See "Epidemiology of tuberculosis".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Pneumonia in children (The Basics)")

SUMMARY Pneumonia is more common in children younger than five years of age
than in older children and adolescents. Risk factors for pneumonia include environmental
crowding, having school-aged siblings, and underlying cardiopulmonary and other medical
disorders. (See 'Epidemiology' above.)

Pneumonia can be caused by a large number of microorganisms (table 1A-B). The agents
commonly responsible vary according to the age of the child and the setting in which the
infection is acquired. (See 'Etiologic agents' above.)

In children younger than five years, viruses are most common. However, bacterial
pathogens, including Streptococcus pneumoniae, Staphylococcus aureus, and S.
pyogenes, also are important. (See 'In children <5 years' above.)
In otherwise healthy children older than five years, S. pneumoniae, M. pneumoniae,
and Chlamydophila pneumoniae are most common. (See 'In children 5
years' above.)
Community-associated methicillin-resistant S. aureus (CA-MRSA) is an increasingly
important pathogen in children of all ages, particularly in those with necrotizing
pneumonia. S. pneumoniae is another frequent cause of necrotizing pneumonia.
(See 'Overview' above.)
Aspiration pneumonia is usually caused by anaerobic oral flora. (See 'Aspiration
pneumonia' above.)
Healthcare-associated pneumonia is usually caused by gram-negative bacilli
or Staphylococcus aureus. (See 'Healthcare-associated pneumonia' above.)

Vitral

Parainfluenza viruses in children


Author:
Flor M Munoz, MD, MSc
Section Editors:
Morven S Edwards, MD
George B Mallory, MD
Deputy Editor:
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jul 06, 2016.

INTRODUCTION Human parainfluenza viruses are important respiratory pathogens in


children and adults. In infants and young children, parainfluenza viruses are the most
common cause of lower respiratory tract infections after respiratory syncytial virus (RSV)
[1-4]. Lower respiratory infections (eg, bronchiolitis, interstitial pneumonitis, pneumonia)
are a leading cause of morbidity and mortality in infants during the first year of life in the
United States and in children younger than the age of six years in developing countries [1].
In adults, parainfluenza viruses generally cause mild upper respiratory infections (URIs)
but can induce more severe disease in the elderly [5]. Immunocompromised patients,
particularly lung and hematopoietic cell transplant recipients can experience life-
threatening lower respiratory tract infections with parainfluenza virus [6-8].

The virology, clinical manifestations, diagnosis, and treatment of parainfluenza viruses in


children will be reviewed here. Infection with parainfluenza viruses in adults is discussed
separately. (See "Parainfluenza viruses in adults".)

MICROBIOLOGY

Virus Parainfluenza viruses (PIV) are single-stranded, enveloped RNA viruses


belonging to the genus paramyxovirus in the Paramyxoviridae family [9]. This family also
includes human mumps, measles, and respiratory syncytial viruses and
metapneumoviruses, as well as avian, bovine, and murine strains of these viruses.

The virions are pleomorphic and range in diameter from 150 to 200 nm. The single strand
of negative-sense RNA is 15,462 nucleotides in length and encodes six common viral
proteins: the nucleocapsid protein (NP), the phosphoprotein (P), the matrix protein (M), the
fusion glycoprotein (F), the hemagglutinin-neuraminidase glycoprotein (HN), and the RNA
polymerase (L) [10].

The HN and F proteins project through the lipid envelope and form the major
antigenic targets for neutralizing antibody [11]. Their hydrophobic tails project into the
virion, where they interact with the M protein to aid in virus assembly [12].
The nucleocapsid core is composed of NP, P, and L proteins in association with viral
RNA. NP proteins bind tightly to the viral genome, creating a template for the RNA-
dependent RNA polymerase composed of the P and L proteins [13].

The HN glycoproteins are involved in attachment of the virus to the host cell via
interactions with sialic acid residues on the cell surface [14]. This interaction allows the F
protein to mediate virus-cell membrane fusion, which is required for nucleocapsid entry
and infection of the host cell. The neuraminidase portion of the HN protein [14] mediates
budding of progeny virions from the surface of infected cells [15].

In addition, each parainfluenza virus expresses at least one non-essential protein: PIV1
and PIV3 RNA encode short C proteins, PIV2 RNA encodes a V protein, and PIV 3 also
expresses a D protein. The C and V proteins inhibit the host innate immune response (host
cell antiviral responses) by suppressing the activity of type I interferons; the function of the
D protein is unknown [16,17].

Viral serotypes Four major serotypes of human PIV (PIV-1, 2, 3, 4) have been
described based upon complement fixation and hemagglutinating antigens [18].
Parainfluenza virus 5 (PIV-5) causes disease in animals (dogs, cats, pigs) but its role in
human disease remains controversial [19].

PIV-3 is the most prevalent serotype, with 90 to 100 percent of children demonstrating
antibody responses by age five [20]. In contrast, PIV-1 and PIV-2 infections are less
common, with only 50 to 74 percent of five-year-olds demonstrating seropositivity. Fifty
percent of six-year-old children and 70 to 90 percent of young adults have antibodies to
PIV-4, despite the fact that infection is infrequently recognized [21,22]. PIV-1 particularly
and PIV-2 are associated with croup in children, whereas PIV-3 is frequently associated
with pneumonia and bronchiolitis in young infants. PIV-4 typically causes mild upper
respiratory infection (URI) in both adults and children, but pneumonia and bronchiolitis
have been described in infants and in children with underlying conditions [22-25].
(See 'Pathogenesis' below.)

PATHOGENESIS Parainfluenza viruses (PIV) initially infect epithelial cells of the nose
and oropharynx [26] and then spread distally to the ciliated and alveolar cells of the
bronchial epithelium of large and small airways [27]. Significant viral replication is seen in
the nose and lungs 24 hours after infection, with viral replication peaking after two to five
days [28]. Viral antigen can be detected in the apical portion of respiratory epithelial cells
from days one to six of infection, with a decrease on day seven [29].

The extent of infection correlates well with disease: mild upper respiratory infections
(URIs) are associated with limited infection of the nasopharynx, whereas more severe
disease involves spread of infection to the large and small airways [30]. PIV-1 and PIV-2,
which are associated with croup, tend to infect the larynx and upper trachea, whereas PIV-
3, which is associated with bronchiolitis and pneumonia, infects the distal airways [28].
Progression to the lower respiratory tract and severity of disease depend upon factors
such as virus titer in the upper respiratory tract, previous exposure to the specific virus,
and genetic susceptibility [9,31,32].

Pathologic examination of infected tissues in animal models of PIV infection suggests that
minimal cellular or tissue damage is caused by direct viral effects [29]. Similarly, PIV
infection does not result in extensive cytopathic effect in in vitro models of respiratory
airway epithelium [16,27,33]. As is the case with other respiratory viruses, the host
immune response plays an important role in the pathogenesis of PIV infection. PIV
induces innate immune responses, CD8+ and CD4+ T cell responses, interferon
production, and local and systemic immunoglobulin A (IgA) and IgG responses, which
contribute to the clearing of the virus [28,34]. The increase in airway responsiveness that
often is associated with PIV-3 infection (and other respiratory viruses, such as respiratory
syncytial virus [RSV]) may result from IgE, increased stromal interleukin-11 production and
enhanced acetylcholine release [35-37]. Preliminary experiments in animal models of
infection suggest that a "two-pronged" approach to therapy, antiviral and anti-inflammatory,
may be useful in PIV-related illness [38].

NATURAL IMMUNITY Natural immunity to parainfluenza virus is incomplete, and


reinfection is common; however, reinfections tend to be milder than initial infection and
restricted to the upper respiratory tract [39]. Antibodies are produced to all viral proteins,
although only antibodies to the surface proteins, HN and F, are neutralizing [9]. T cell
immunity contributes to viral clearance and confers transient resistance to reinfection,
albeit short lived [16,40].

EPIDEMIOLOGY

Transmission Parainfluenza viruses (PIV) are transmitted by direct person-to-person


contact and through exposure to contaminated nasopharyngeal secretions through
respiratory droplets and fomites [41].

Incubation period The incubation period ranges from two to six days [41].

Prevalence Human PIV are recovered most commonly in children younger than five
years of age with upper respiratory infections (URIs) [3,42]. Serologic studies have shown
that as many as 50 percent of children have been infected with PIV-3 by their first birthday,
whereas PIV-1 and PIV-2 most often affect preschool-aged children three to five years of
age [43].

In population-based surveillance, PIV-1, 2, or 3 were identified in 8 percent of 7716


specimens obtained from pediatric outpatients with influenza-like illness between August
2010 and July 2014 [42]. Among these, 30 percent were PIV-1, 26 percent PIV-2, and 44
percent PIV-3. The annual incidence of each serotype varied between 88 and 100 per
100,000 children. In children younger than five years, the incidence of PIV was 259 to
1307 per 100,000. The median age at detection was lower for PIV-3 (3.4 years) than for
PIV-1 (4.5 years) and PIV-2 (7.0 years).

PIV infections account for 20 to 40 percent of lower respiratory tract illnesses (eg,
bronchiolitis, pneumonia) in children from which a virus is recoverable, and 2.8 per 1000
children with such infections require hospitalization [44]. PIV is responsible for
approximately 30,000 (range 7600 to 48,000) pediatric hospitalizations annually in the
United States [45]. A study based upon the National Hospital Discharge survey from 1994
through 1997 estimated hospitalization rates due to PIV-1 to 3 to range from 1.9 to 12 per
1000 children younger than one year and from 0.5 to 2.0 per 1000 children ages one to
four years [46]. The highest overall hospitalization rates were for PIV-3, estimated at 0.48
to 2.6 per 1000 children. A population-based study in the United States (2000 to 2004)
estimated that PIV accounts for up to 7 percent of all hospitalizations for fever, acute
respiratory illness, or both in children younger than five years of age [3]; PIV3 is the cause
of one-half of these hospitalizations. Data from the National Respiratory and Enteric Virus
Surveillance System (NREVSS, 1998-2010) indicate an annual estimated PIV-associated
hospitalization rate of 0.2 per 1000 children for bronchiolitis, 0.4 per 1000 children for
croup, and 0.5 per 1000 children for pneumonia [47].The majority of PIV-associated
hospitalizations occurred in children younger than two years.

PIV infections occur throughout the world and throughout the year, with certain serotypes
predominating during the spring or fall. PIV-1 usually causes outbreaks biennially during
the fall of odd-numbered years (figure 1) [48,49]. In contrast, PIV-2 and PIV-3 occur in
annual epidemics in the fall and spring, respectively [48]. During years in which PIV-1 is
not circulating, there is an increase in PIV-3 activity, manifested either as a longer spring
PIV-3 season or as a second smaller peak in the fall. Seasonal patterns of PIV-4 infections
have not been established, since the disease is usually mild, and the virus is difficult to
detect. However, it is diagnosed more frequently between October and January [23]. In
tropical countries, parainfluenza viruses do not exhibit seasonal variation [50].

Ethnicity and sex may play roles in the severity of PIV infection. Bronchiolitis occurs most
commonly in non-Caucasian males [30]. Breast-fed infants have a reduced risk of serious
infection. Spread within families is extensive, requiring only direct person-to-person
contact or large droplet inhalation [51].

Pneumococcal vaccination has been associated with a reduction in the incidence of


pneumonia in infants with PIV and other respiratory virus infections [52]. This observation
suggests that the pneumococcus is an important pathogen in virus-associated pneumonia.
(See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children".)

CLINICAL PRESENTATION Parainfluenza viruses (PIV) cause a variety of upper and


lower respiratory tract illnesses, ranging from mild cold-like syndromes to life-threatening
pneumonia; they cause a greater proportion of respiratory infections in outpatients than in
hospitalized patients.
In children, more than 50 percent of PIV infections are upper respiratory infections (URIs),
of which 30 to 50 percent are complicated by otitis media [44,53]; approximately 15
percent of PIV infections involve the lower respiratory tract. Strong relationships exist
between PIV infection and specific clinical syndromes in children.

PIV-1 is the leading cause of croup or laryngotracheobronchitis in children [1].


Children initially present with fever, rhinorrhea, and pharyngitis and progress to
cough, often "barking" in nature, with stridor, dyspnea, and chest wall retractions.
Respiratory distress requiring hospitalization can occur and, rarely, hypoxemia from
viral involvement in the lung parenchyma is seen. (See "Croup: Clinical features,
evaluation, and diagnosis", section on 'Clinical presentation'.)
PIV-2 also is associated with croup, although the illness generally is milder than with
PIV-1.
PIV-3 is associated with pneumonia and bronchiolitis in the first six months of life,
mimicking respiratory syncytial virus (RSV) infection. (See "Respiratory syncytial virus
infection: Clinical features and diagnosis", section on 'Respiratory disease'.)
PIV-4 typically causes only mild URI symptoms in both adults and children.
However, PIV-4 has been isolated in cases of bronchiolitis, pneumonia, croup, apnea,
and paroxysmal cough in young infants and in children with underlying conditions,
such as developmental disabilities, chronic cardiopulmonary disease, or
immunosuppression [23,24].

Otitis media and sinusitis can result from either primary viral infections or secondary
bacterial superinfection. Nonrespiratory complications of PIV are rare but include
meningitis [54], myocarditis and pericarditis [55], Guillain-Barr syndrome [56], and acute
disseminated encephalomyelitis [57]. (See "Clinical manifestations and diagnosis of
myocarditis in children" and "Guillain-Barr syndrome in adults: Treatment and
prognosis" and "Viral meningitis: Clinical features and diagnosis in children", section on
'Clinical features'.)

Although most PIV infections are mild, severe disease can occur, particularly in
immunocompromised patients. Immunocompromised children and adults, including those
with human immunodeficiency virus (HIV) infection can progress from mild URI symptoms
to severe pneumonia with prolonged viral shedding and dissemination [58-61]. Children
with severe T cell deficiencies can succumb to fatal giant cell pneumonia after infection
with PIV [62].

In a study of children with hematologic malignancies at a pediatric cancer center, PIV was
the second most common respiratory viral infection after influenza, detected in 10 percent
of children tested [63]. Ninety percent of PIV infections were community acquired. PIV 3
accounted for 61 percent of PIV infections. PIV infections were approximately four times
more common in children with acute lymphoblastic leukemia than in those with other
hematologic malignancies. Although most (80 percent) of children had upper respiratory
tract illness, children who were young (median age 27 months) and presented with fever,
severe neutropenia, or lymphopenia were at increased risk for lower respiratory tract
infection.

In one report, 2.2 percent of 1253 children and adults who underwent bone marrow
transplantation developed symptomatic PIV infection [64]. These patients are at particular
risk of severe PIV-associated pneumonia, with prolonged shedding and mortality rates of
up to 30 percent [62,64-70].

Solid organ transplant recipients are at an increased risk for pulmonary complications.
Complications such as bronchiolitis obliterans, and acute and chronic rejection have been
reported in lung transplant patients with PIV and other respiratory viral infections [6,71].

DIAGNOSIS The diagnosis of parainfluenza virus (PIV) infection can be made clinically
with a compatible presentation during an outbreak of PIV in the community. Laboratory
confirmation may be useful in determining if a community outbreak exists or in excluding
other infections in seriously ill patients.

When laboratory diagnosis is necessary, nasopharyngeal and/or oropharyngeal specimens


can be obtained for polymerase chain reaction (PCR) as the preferred diagnostic test
given its high sensitivity and rapid turn-around time. If PCR is not available, rapid antigen
detection and viral culture may establish the diagnosis. Serology is not routinely used for
the diagnosis of PIV.

PCR assays permit the detection of PIV and a number of respiratory viruses in
nasopharyngeal and oropharyngeal secretions with reported sensitivities of 95 to 100
percent and excellent specificity [72-75]. Collection of paired oropharyngeal and
nasopharyngeal samples may increase the sensitivity [76,77]. PCR increases the yield of
detection of PIV-3 by 1.5-fold, compared with viral culture [78].

PIV also can be identified by culture from the nasopharynx (nasopharyngeal swabs,
aspirates, or washes). Specimens should be placed in viral transport media and kept at
4C because the virus loses infectivity at room temperature [79]. Hemadsorption and
immunofluorescence typing are routinely used for identification, as observed cytopathic
effects can be variable.

Rapid antigen detection of PIV 1-3 by immunofluorescence is available with reported


sensitivity that is generally lower than that of PCR [80-83].

Serologic testing also can be performed but is time-consuming and can be confounded by
the presence of heterologous antibodies [21].

TREATMENT There are no antiviral agents with proven efficacy for parainfluenza virus
(PIV) infections, which are self-limited in most cases. Glucocorticoids and
nebulized epinephrine may be used to treat croup (see "Croup: Approach to
management"). The management of bronchiolitis is supportive. (See "Bronchiolitis in
infants and children: Treatment, outcome, and prevention".)

Ribavirin and other agents that have been used to treat PIV in immunocompromised hosts
are discussed separately. (See "Parainfluenza viruses in adults", section on 'Treatment'.)

Transplant recipients may benefit from reduction of immune suppression in addition to


supportive care.

DAS181 is a sialidase fusion protein that cleaves the sialic acid containing receptors of
PIV in respiratory cells. It has antiviral activity against influenza and parainfluenza viruses
and has been reported to successfully treat PIV in patients with hematopoietic stem cell
and lung transplantation [84-92]. In one report, four severely immunocompromised
children who had received hematopoietic cell transplantation were treated with DAS181 for
lower respiratory tract infection. Inhaled DAS181 was administered for 5 to 10 days. All
patients tolerated the treatment well and had clinical improvement, with decreased oxygen
requirement. Improvement in viral load was also documented [90]. DAS181 treatment of
PIV in immunocompetent patients is being evaluated in a phase II clinical trial [93].

VACCINE DEVELOPMENT There is no licensed vaccine for parainfluenza viruses


(PIV) [10,94]. However, vaccine candidates are being studied in human populations, and a
vaccine for use in infants, young children, and immunocompromised adults may be
forthcoming.

Vaccine development began in the 1960s with the production of an inactivated mixture of
PIV-1, -2, and -3. This vaccine produced variable antibody responses and did not protect
against challenge [10]. Subunit vaccines containing purified HN and F glycoproteins of PIV
were later shown to induce functional antibodies in animal models [10]. Using a different
approach, a modified vaccinia recombinant, Ankara (MVA), expressing the HN or F protein
of PIV-3 tested in non-human primates showed significant protection of the lower
respiratory tract but failed to demonstrate significant upper respiratory tract protection
against challenge with PIV-3 [95].

Several live attenuated intranasal vaccine candidates have been developed using cell
culture passage or chemical mutagenesis for viral attenuation and reverse genetics
technology:

Bovine PIV-3 (BPIV-3), a virus that is antigenically related to human PIV-3 (hPIV-3),
has been evaluated in clinical trials as a vaccine candidate to protect against PIV-3 in
children and infants. However, seroconversion rates to hPIV-3 have been modest
[94,96,97].
Murine PIV (Sendai virus), another virus that is antigenically related to human PIV,
has been evaluated in clinical trials as a nasally administered live attenuated
xenotropic vaccine against human PIV-1, similar to the use of bovine PIV-3 [98].
A live attenuated, cold-adapted PIV-3 vaccine candidate, hPIV-3-cp45, the cp45
derivative of the JS strain of wild-type human PIV-3, was developed in the 1990s.
When administered intranasally, it provided almost complete protection against
challenge with wild-type PIV-3 in both the upper and lower respiratory tracts in non-
human primates [10]. HPIV-3-cp45 was found to be appropriately attenuated and
immunogenic in children and infants as young as one month of age [99-101].
Similarly, this vaccine was found to be safe and immunogenic in a phase 2 trial of
healthy seropositive and seronegative infants and children, with two or three doses
needed to induce durable immunity [102]. A combined hPIV-3-
cp45/respiratory syncytial virus (RSV) experimental vaccine has been studied in 6- to
18-month-old seronegative children, showing antibody responses similar to the
monovalent vaccine components [103].

Reverse genetics technology has allowed the development of a cDNA derived


recombinant virus rHPIV3-cp45 that is the focus of current clinical development [16]. The
advantages of this technology include the ability to rapidly produce the vaccine virus with
minimal risk of biologic contamination. Phase 1 and 2 clinical trials have shown that this
live, attenuated recombinant rHPIV3-cp45 vaccine is well tolerated and immunogenic in
infants 6 to 36 months of age, but a three dose regimen might be necessary to elicit
protection in infants younger than 6 months of age [16,104,105].

To improve immunogenicity, two cDNA-derived chimeric bovine/human PIV3


virus (rB/HPIV3) constructs have been created by reverse genetics and tested in adults,
and HPIV3 seropositive and seronegative infants and children, with promising results
[106]. Chimeric rB/HPIV3 viruses modified to express the RSV F or both the F and G
proteins are bivalent vaccine candidates currently undergoing testing in children to prevent
RSV and PIV3 [107].

Through reverse genetics, several PIV-1 and PIV-2 candidate vaccines also have been
developed and some are undergoing clinical testing [16,94,108-110]. A live-attenuated
human PIV-1 vaccine (rHPIV-1/84/del 170/942A) was studied in a phase I clinical trial, but
insufficiently immunogenic in PIV-seronegative children [111]. A live attenuated
recombinant bivalent PIV-1/RSV vaccine (rHPIV1-RSV-F) is undergoing preclinical
evaluation [112].

SUMMARY AND RECOMMENDATIONS

Parainfluenza viruses (PIV) are single-stranded, enveloped RNA viruses belonging


to the genus paramyxovirus in the Paramyxoviridae family. Four major serotypes of
human PIV (PIV-1, 2, 3, 4) have been described. (See 'Microbiology' above.)
Parainfluenza viruses initially infect epithelial cells of the nose and oropharynx and
then spread distally to the large and small airways. (See 'Pathogenesis' above.)
PIV cause a variety of upper and lower respiratory tract illnesses, ranging from mild
cold-like syndromes to life-threatening pneumonia. PIV-1 and PIV-2 are associated
with croup and PIV-3 with pneumonia and bronchiolitis. PIV-4 typically causes mild
upper respiratory infection, but pneumonia and bronchiolitis have been described in
infants and in children with underlying conditions. Although most PIV infections are
mild, serious complications can occur, particularly in immunocompromised patients.
(See 'Clinical presentation' above.)
The diagnosis of PIV infection can be made clinically with a compatible presentation
during an outbreak of PIV in the community. Laboratory confirmation may be useful in
determining if a community outbreak exists or in excluding other infections in
seriously ill patients. (See 'Diagnosis' above.)
There are no licensed antiviral agents with proven clinical efficacy for PIV infections.
PIV infections are generally self-limited and treated with supportive measures. The
management of specific clinical syndromes (eg, croup, bronchiolitis) is discussed
separately. (See 'Treatment' above and "Croup: Approach to
management" and "Bronchiolitis in infants and children: Treatment, outcome, and
prevention".)
Vaccine development is ongoing and the outlook is promising, given the availability
of reverse genetics technology. (See 'Vaccine development' above.)

pidemiology and clinical manifestations of adenovirus infection

Authors:
Phyllis Flomenberg, MD
Tsoline Kojaoghlanian, MD
Section Editors:
Martin S Hirsch, MD
Sheldon L Kaplan, MD
Deputy Editor:
Anna R Thorner, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Apr 27, 2016.

INTRODUCTION Adenoviruses are a family of viruses that are an important cause of


febrile illnesses in young children. They are most frequently associated with upper
respiratory tract syndromes, such as pharyngitis or coryza, but can also cause pneumonia.
Less commonly, adenoviruses cause gastrointestinal, ophthalmologic, genitourinary, and
neurologic diseases. Most adenoviral diseases are self-limiting, although fatal infections
can occur in immunocompromised hosts and occasionally in healthy children and adults.

In addition to their importance as infectious agents, adenoviruses are being studied


intensively as vectors to deliver foreign genes both for gene therapy and for immunization
against tumors and certain infections, such as HIV-1 and malaria. (See "Adenovirus
pathogenesis and vector applications".)

The epidemiology and clinical manifestations of adenovirus infections will be reviewed


here. Issues relating to pathogenesis, diagnosis, and treatment are discussed separately.
(See "Diagnosis, treatment, and prevention of adenovirus infection".)

VIRION STRUCTURE Adenoviruses have a double-stranded DNA genome of


approximately 35 kb surrounded by a nonenveloped icosahedron with fiber-like projections
from each of the 12 vertices. The fiber protein is attached noncovalently to the
icosahedron by a pentameric polypeptide named penton base. The fiber protein from most
adenoviruses, except subgroup B, binds to the cellular receptor CAR (coxsackie-
adenovirus receptor), which also binds coxsackie B virus [1]. Group B adenoviruses have
been shown to bind to CD46, a complement-related protein [2,3]. The penton base
mediates internalization via interaction with specific cellular integrins [4].

The major surface protein of the virion is the trimeric polypeptide hexon. Group-reactive
antigenic determinants are present on the hexon proteins from all human adenoviruses.
Type-specific neutralizing epitopes are present both on the fiber and hexon proteins with
minor sites on the penton base. In addition, many adenoviruses hemagglutinate rat or
rhesus red blood cells; this property is related to the fiber protein.

Most adenoviruses readily infect human epithelial cell lines, exhibiting a characteristic
cytopathic effect. This property is often used to isolate adenoviruses from clinical
specimens in diagnostic virology laboratories.

EPIDEMIOLOGY Adenoviruses have a worldwide distribution, and infections occur


throughout the year. Adenoviruses cause 5 to 10 percent of all febrile illnesses in infants
and young children [5]. Most individuals have serologic evidence of prior adenoviral
infection by the age of 10.

Adenovirus infections are prevalent in daycare centers and in households with young
children. Nosocomial transmission also has been documented.

Many epidemics of adenoviral disease have been described, including


pharyngoconjunctival fever in summer camps and in association with public swimming
pools [6], keratoconjunctivitis in medical facilities [7,8], and serious acute respiratory
disease in military recruits [9,10]. (See 'Military recruits' below.)

Transmission Transmission of adenovirus can occur via aerosol droplets, the fecal-oral
route, and by contact with contaminated fomites. Adenoviruses can survive for long
periods on environmental surfaces; they are resistant to lipid disinfectants because they
are nonenveloped, but they are inactivated by heat, formaldehyde, or bleach (sodium
hypochlorite).
There are several other modes of adenovirus transmission:

Neonates can acquire adenoviral infection from exposure to cervical secretions at


birth [11-13]. The presence of adenovirus has been documented in cervical cells from
the mother of a neonate who died from adenoviral pneumonia [11]. Intrauterine
infection has also been detected in fetal tissue by polymerase chain reaction (PCR)
assay [14].
Serologic evidence that adenoviruses can be transmitted from donor kidney and
liver transplants suggests that these organs occasionally harbor adenoviruses in a
latent form [15].

Serotype prevalence

Overview Over 50 human adenovirus serotypes have been identified based upon
antigenic determinants detected by viral neutralization assay. Serotypes are further
classified into six subgroups, A to F, based upon differences in patterns of
hemagglutination. Serotypes within each subgroup are closely related at the DNA level
and frequently share similar biologic properties. As examples, subgroup B types 11, 34,
and 35 cause hemorrhagic cystitis, whereas subgroup D types 8, 19, and 37 are
associated with keratoconjunctivitis (table 1).

The prevalence of the different serotypes cannot be determined with confidence since the
vast majority of patients with adenovirus infection are not cultured. This issue was
addressed in a study in which 1653 clinical adenovirus isolates were collected from 22
hospital laboratories between 2004 and 2006 [16]. The following distribution was noted:

Serotype 3 (subgroup B) 35 percent


Serotype 2 (subgroup C) 24 percent
Serotype 1 (subgroup C) 18 percent

These serotypes are primarily associated with upper respiratory tract diseases (table 1).
However, the distribution of adenovirus serotypes is different in military recruits.

Military recruits Beginning in 1971, military recruits in the United States received a
highly effective, enteric-coated, oral live vaccine with adenovirus types 4 (subgroup E) and
7 (subgroup B); manufacture of this vaccine was discontinued in 1996 [17]. Since that
time, both susceptibility and clinical infection due to adenovirus have increased in military
recruits. Rare fatalities have been reported in recruits due to probable adenovirus
pneumonia with or without accompanying encephalitis [17].

The following observations illustrate the range of findings:

A study of 341 military recruits in 2004 found that more than three-quarters were
susceptible to either adenovirus type 4 or type 7 infection and, during active
surveillance, one-quarter developed a febrile respiratory illness attributable to
adenovirus serotype 4 [18]. Furthermore, the percentage of recruits seropositive for
this strain increased from 34 percent at enrollment to 97 percent by the end of the
study. Potential sources of transmission included environmental contamination and
extended pharyngeal shedding of virus.
Among 584 clinical adenovirus isolates from military recruits collected between 2004
and 2006, 93 percent were serotype 4 [16]. However, the distribution appears to be
changing. In a series of 1867 military recruits with adenovirus respiratory infections,
serotype 4 was the most prevalent serotype between 2002 and 2005 [19], while in
2006 subgroup B adenoviruses became more prevalent, including types 3, 7, 21, and
14. The emergence of adenovirus 14 is discussed in detail below. (See 'Adenovirus
14' below.)

As a result of the increasing prevalence of adenovirus infection in military recruits, the


vaccine program in the military was reinstituted [17,18,20]. In 2011, a new live
oral adenovirus vaccine against adenovirus serotypes 4 and 7 was approved for use in
United States military personnel aged 17 through 50 years [21,22]. (See "Diagnosis,
treatment, and prevention of adenovirus infection", section on 'Vaccination'.)

Adenovirus 14 Adenovirus 14 is a subgroup B serotype that was first identified in


military recruits in the Netherlands in 1955. Since then, it has caused sporadic outbreaks
in civilians and military recruits throughout Europe during the 1950s and 1960s. It emerged
in 2005 in the United States and has caused several outbreaks of pneumonia in both
military recruits and civilians.

Adenovirus 14 was detected in the United States in 2006 when it was associated with a
fatal respiratory illness in a 12-day-old infant in New York [23]. Clusters of severe acute
adenovirus 14 respiratory disease have been subsequently identified in Oregon,
Washington, Texas, and Alaska [23-25]. In a report that included 140 patients, 38 percent
were hospitalized, 17 percent were admitted to intensive care units, and 5 percent died
[23]. In a retrospective review published subsequently, it was shown that adenovirus 14
had emerged in Oregon in 2005 and became the prevalent serotype in 2006 and 2007,
causing over 50 percent of adenovirus infections [26].

The cluster in Texas involved military recruits at an Air Force base [27]. Preexisting
antibodies against adenovirus 7 were detected in 7 of 19 individuals with mild illness but in
none of 16 individuals with pneumonia caused by adenovirus 14, suggesting that
adenovirus 7specific antibodies might provide some degree of cross-protection against
adenovirus 14. Among military recruits in Texas hospitalized with pneumonia during the
outbreak, adenovirus 14 was not associated with excess morbidity or mortality compared
with other causes of pneumonia [28]. However, women with adenovirus 14 infection had
higher rates of hospitalization than men (83 versus 40 percent).

Adenovirus 14 has also been identified in military recruits at a number of other bases
[19,29], in healthcare workers (HCW) and a household contact of a HCW [30,31], and in
two children and an adult in California with severe pneumonia superimposed upon chronic
pulmonary disease [32]. It also caused an outbreak of pneumonia among a group of
individuals who socialized and smoked together in Alaska [25]. A study of healthcare
personnel at a military hospital where 15 trainees were hospitalized with pneumonia
caused by adenovirus 14 suggested likely nosocomial transmission [31].

An analysis of 99 isolates from military and civilian cases of adenovirus 14 infection in the
United States showed that all isolates were identical and suggested that they arose from
recombination among adenovirus 11 and adenovirus 14 ancestral strains [33].

CLINICAL PRESENTATION The clinical manifestations of adenoviral disease vary


according to the age and immunocompetence of the host (table 2). Severe disease has
been associated with type 7 [34-38], type 5 [16], type 21 [16,39], and, more recently as
noted in the previous section, type 14 [23,32].

Adenoviruses can cause persistent infections, with the virus being shed in the feces for
months to years after acute infection [5].

Respiratory tract Adenoviruses are among the most common viruses isolated from
young children with febrile respiratory illnesses. The usual duration of illness is five to
seven days, although symptoms may persist for up to two weeks. Bacterial superinfections
can occur.

Pharyngitis and coryza Pharyngitis and coryza are common presentations of


adenovirus infection [40,41]. Pharyngitis is frequently associated with conjunctivitis,
laryngotracheitis, bronchitis, or pneumonia. Fever and other systemic manifestations such
as malaise, headache, myalgia, and abdominal pain are common [42]. In many cases,
exudative tonsillitis and cervical adenopathy may be present, a syndrome that can be
clinically indistinguishable from group A streptococcal infection. Adenoviruses are the most
common cause of tonsillitis in young children.

Otitis media and less common presentations Otitis media is another common
presentation, especially in children under age 1 [40,41]. However, the presence of
adenovirus in middle ear fluid has only been documented in a few cases [43]. Less
frequently, adenoviruses cause a pertussis-like syndrome, bronchiolitis, coryza without
fever, or an exanthem.

Pneumonia A number of adenovirus serotypes (1, 2, 3, 4, 5, 7, 14, 21, and 35) have
been reported to cause pneumonia [23,32,44-46]. Subgroup B types 3, 7, 14, and 21 have
been associated with severe and complicated pneumonia [23,32,47-50]. In a study of 2638
hospitalized children with pneumonia, adenoviruses were detected in 15 percent of
children younger than five years of age compared with 3 percent of older children [51]. In a
prospective study that compared the prevalence of viruses in the upper respiratory tracts
of children and adults with community-acquired pneumonia with the prevalence in
asymptomatic controls, detection of adenovirus was associated with pneumonia only in
children <2 years of age [52]. This suggests that adenovirus may not be the causative
pathogen of pneumonia in all patients in whom it is detected (especially in those 2 years
of age).

Pneumonia is more severe in infants than older children and may be associated with
lethargy, diarrhea, and vomiting. Extrapulmonary complications occasionally occur,
including meningoencephalitis, hepatitis, myocarditis, nephritis, neutropenia, and
disseminated intravascular coagulation [53,54].

Chest radiography in adenoviral pneumonia reveals diffuse bilateral pulmonary infiltrates


similar to those of other viral pneumonias. Pathologic changes include necrotizing
bronchitis, bronchiolitis, and pneumonia with mononuclear cell infiltration, hyaline
membranes, and necrosis. Advances in and the availability of viral molecular diagnostics
have improved the diagnosis of adenoviral pneumonia; differentiating adenoviral from
other suspected causes of childhood pneumonia significantly improves management
strategies in the young as well as the immunocompromised.

Neonates and infants with underlying diseases are at high risk for fatal adenoviral
pneumonia. On the other hand, pneumococcal vaccination has been associated with a
reduction in the incidence of pneumonia in infants with adenovirus and other respiratory
virus infections [55]. This observation suggests that the pneumococcus is an important
pathogen in virus-associated pneumonia. (See "Pneumococcal (Streptococcus
pneumoniae) conjugate vaccines in children", section on 'Pneumonia'.)

There is a high incidence of pulmonary sequelae following adenoviral pneumonia in young


children, including bronchiectasis and bronchiolitis obliterans [39,56,57]. In a meta-
analysis of pneumonia in children under age 5, adenovirus infection was associated with
the highest risk (55 percent) of long-term sequelae compared with other causes of
pneumonia (Mycoplasma pneumoniae, Chlamydia pneumoniae, Staphylococcus aureus)
[58].

Acute respiratory disease In young adults, a syndrome of acute respiratory disease


can occur, especially under the special conditions of fatigue and crowding present in
military training camps [9]. Symptoms include fever, pharyngitis, cough, hoarseness, and
conjunctivitis. Pneumonitis can also occur, resulting in rare deaths [23,28,32]. Epidemics of
acute respiratory disease have been associated with adenovirus subgroup E type 4 and
subgroup B types 3, 7, 11, 14, and 21. Since the reinstitution of the United States military
adenovirus vaccination program in 2011, the incidence of febrile respiratory illnesses and
adenovirus disease has decreased dramatically among United States military basic
trainees [59].

Eyes Pharyngoconjunctival fever is a classic adenoviral syndrome that consists of a


benign follicular conjunctivitis often accompanied by a febrile pharyngitis and cervical
adenitis. Outbreaks of pharyngoconjunctival fever have been described, especially in
summer camps in association with swimming pools or lakes [6]. Adenovirus subgroup B
types 3 and 7 are the most common isolates, but multiple serotypes from subgroups B, C,
D, and E have been implicated.

Epidemic keratoconjunctivitis (EKC) is a more serious disease associated primarily with


the subgroup D types 8, 19, and 37. It is characterized by bilateral conjunctivitis with
preauricular adenopathy, followed by the development of painful corneal opacities.
Although the disease is self-limited and virtually never results in permanent corneal
damage, it can run a protracted course lasting up to four weeks. It causes severe pain and
blurry vision and incurs significant economic losses in the workplace.

EKC may be transmitted in medical offices and hospitals by the ophthalmologist's hands
and contaminated instruments or eye drops [7,8,60]. In one report of EKC due to
adenovirus type 8 in a neonatal intensive care unit where premature infants underwent
repetitive eye exams, the outbreak spread from neonates to the staff and then to their
families [7]. In another review of an adenovirus type 8 epidemic, the authors demonstrated
that almost 50 percent of patients diagnosed with EKC carried virus on their hands and
that the virus remained viable on inanimate surfaces for up to 35 days [61].

Gastrointestinal tract In young children, 5 to 10 percent of acute diarrheal illnesses


are caused by the subgroup F adenoviruses types 40 and 41. These enteric adenoviruses
were first identified in stool specimens by electron microscopy and require special cell
lines for growth. Specific adenovirus antigen assays or PCR assays can be used for
detection of these agents. (See "Diagnosis, treatment, and prevention of adenovirus
infection", section on 'Diarrhea in young children'.)

In one study of over 400 cases of acute infantile gastroenteritis, enteric adenoviruses were
the sole recognizable cause of diarrhea in 7.2 percent of cases; no isolates were found
among 200 controls [62]. Diarrhea was prolonged, lasting from 8 to 12 days. A review of
another outbreak in several daycare centers found that 38 percent of 249 young children
had positive stool specimens, although only one-half were symptomatic [63].

Enteric adenoviruses also may be a cause of nosocomial infection, as suggested by one


report of 14 cases of enteric adenovirus-related diarrhea in hospitalized infants over a
three-month period [64].

Unlike types 40 and 41, epidemiologic studies have not shown a clear correlation between
most other serotypes and gastroenteritis. However, the subgroup A type 31 has been
associated with infantile diarrhea in some reports [65]. In addition, lower serotype
adenoviruses have been associated with mesenteric adenitis, which may mimic
appendicitis and occasionally cause intussusception [66].

Adenoviruses may be excreted in feces for months after a primary infection. Thus, a
positive stool culture for adenovirus is not usually clinically significant as a cause of
diarrhea. However, in immunocompromised hosts, symptomatic gastroenteritis has been
associated with a range of adenovirus serotypes.

Hepatitis is a well-described complication of adenovirus infections in immunocompromised


hosts, especially with subgroup C type 5 [67]. Adenovirus hepatitis is a particular problem
in pediatric liver transplant recipients and may be fatal in these individuals. In a review of
89 cases of adenovirus hepatitis, 48 percent occurred in liver transplant recipients and 21
percent in hematopoietic cell transplant recipients [68]. The majority of infections occurred
within six months following transplantation. Only 24 patients (27 percent) survived; in most
patients who survived, immunosuppression was reduced, suggesting that reduction in
immunosuppression may contribute to improved outcomes.

Genitourinary tract Adenovirus subgroup B types 11 and 21 have been associated


with acute hemorrhagic cystitis in children [69]. This self-limited disease is more common
in males and is usually not accompanied by fever or hypertension. Its significance lies in
the potential confusion with other, more serious diseases of the kidney, such as
glomerulonephritis.

In adults, adenovirus subgroup D types 19 and 37 have been occasionally associated with
urethritis [70,71]. In immunocompromised patients, adenovirus subgroup B types 11, 34,
and 35 can cause hemorrhagic cystitis and tubulointerstitial nephritis [72,73].

Nervous system Meningitis and encephalitis have been reported occasionally in


association with adenovirus infection [74]. Neurologic involvement may be a primary
manifestation or found in association with severe pneumonia, especially when infection is
due to subgroup B type 7 [53].

Disseminated Disseminated adenovirus infection has been reported in both


immunocompromised and immunocompetent children [75] and in adults who have
undergone hematopoietic cell or solid organ transplantation [76]. In a retrospective review
of children with adenovirus infection, 2.5 percent (11 of 440) had disseminated disease
[75]. Of these, 54 percent (6 of 11) were immunocompromised. Mortality from
disseminated disease was 73 percent overall (83 percent among immunocompromised
and 60 percent among immunocompetent hosts).

Myocarditis In two series of acute myocarditis in children, adenovirus was the most
common cause of viral myocarditis, occurring in 60 percent of PCR-proven cases of viral
myocarditis [77,78].

Other Adenovirus has occasionally been associated with viral myositis accompanied by
rhabdomyolysis [79,80] (see "Viral myositis"). Fewer than 10 cases of adenovirus-
associated arthritis have also been reported [81,82] (see "Specific viruses that cause
arthritis").
INFECTIONS IN IMMUNOCOMPROMISED HOSTS A variety of clinical syndromes can
occur in immunocompromised individuals with adenovirus infection [83]. Reactivation of
endogenous virus plays a role in adenoviral diseases in these patients. The major
reservoirs for persistent adenovirus infections and the mechanisms of viral persistence are
unknown; however, CD4 lymphocytes found in tonsils can harbor adenoviruses for a
prolonged period [84].

Transplant recipients The spectrum of adenovirus infection can range from


asymptomatic shedding to fatal disseminated disease in patients who have undergone
organ or hematopoietic cell transplantation (HCT) [76]. Disease can be caused by primary
infection, reactivation of latent infection in the transplant recipient, or reactivation of
infection transmitted in the donated organ [15].

In a retrospective hospital-based study, adenoviral infections were compared between


pediatric HCT and solid organ transplant recipients [85]. Infection occurred at a median of
1.6 months post-transplantation consistent with reactivation disease. All deaths from
adenoviral disease occurred exclusively among HCT recipients, likely related to their more
severe immune dysfunction.

Hematopoietic cell transplantation Adenoviral diseases are well characterized in


hematopoietic cell transplant recipients. A wide range of clinical syndromes has been
reported, including pneumonia, colitis, hepatitis, hemorrhagic cystitis, tubulointerstitial
nephritis, encephalitis, and disseminated disease [76,86-89]. In addition to the common
lower serotypes, there was a preponderance of subgroup B types 11, 34, and 35, which
are infrequent isolates in the general population [86,87]. (See "Pulmonary complications
after allogeneic hematopoietic cell transplantation".)

In one study of 1050 adult HCT recipients, 51 (4.8 percent) shed adenoviruses and 10 (0.9
percent) had invasive adenoviral disease [86]. Another report documented a higher
incidence of adenoviral infection and disease in a HCT patient population (both children
and adults) treated with T celldepleted bone marrow grafts and more intensive
immunosuppressive regimens; 42 of 210 patients (20.9 percent) had evidence of infection,
while 13 (6.5 percent) developed invasive disease [87]. Adenoviral infections occurred
more frequently and appeared earlier post-transplant in pediatric patients. Treatment and
outcomes of adenovirus infections in adult HCT recipients are discussed separately.
(See "Diagnosis, treatment, and prevention of adenovirus infection", section on
'Treatment'.)

Adenoviruses cause more frequent disease in pediatric HCT recipients compared with
adults [88,90]. In one study of 204 pediatric HCT recipients, 31 had adenovirus infections
(15.1 percent) and 18 (8.8 percent) developed severe disease [90]. Allogeneic recipients
and, in particular, recipients of unrelated or mismatched related grafts had an increased
risk of infection. In a study of 123 pediatric allogeneic recipients, adenovirus infection was
a major independent risk factor for treatment-related mortality [91].
Solid organ transplantation Adenovirus infections in solid organ transplant recipients
may range from asymptomatic to severe and disseminated, with prolonged viral shedding
and significant morbidity and mortality, including associated graft dysfunction and rejection
[92]. Adenovirus more frequently affects pediatric than adult solid organ transplant
recipients. Infection after transplant may be associated with reactivation of a prior latent
infection in the recipient or the graft or with a newly acquired infection.

Three clinical scenarios are possible: asymptomatic viremia or infection documented by


detection of adenovirus from specimens by culture, polymerase chain reaction (PCR), or
specific antigen tests in the absence of clinical symptoms; adenovirus disease with specific
organ involvement and manifestations (eg, pneumonia, enteritis, meningoencephalitis)
documented by viral detection and/or histopathology; and disseminated disease, when two
or more organs are involved [92]. Adenovirus infection is more likely to occur during the
first several months after transplantation. The incidence appears higher among liver
transplant recipients, followed by heart and kidney transplant recipients [85,93]. Severe
disease has been reported in lung, heart, and multivisceral organ recipients [92].

In contrast to the HCT population, adenoviral disease typically involves the donor organ in
solid organ transplant recipients. As an example, the primary clinical manifestation in those
who have undergone renal transplantation is acute hemorrhagic cystitis, sometimes
complicated by interstitial nephritis [72]. This syndrome is almost exclusively associated
with subgroup B types 11, 34, and 35. The incidence has not been well defined but is low.
The prognosis is generally good, although infection occasionally results in fatal
disseminated disease [94].

Similarly, adenoviral pneumonia is described as an early complication following lung


transplantation. In one study of 308 lung transplant recipients, four (1.3 percent) developed
adenovirus pneumonia, three of whom were children [95]. (See "Bacterial infections
following lung transplantation".)

The most common manifestation of invasive adenoviral disease is hepatitis in pediatric


patients who have undergone liver transplantation. In one large study of 484 liver
transplant recipients, 14 patients (three percent) developed adenovirus hepatitis [96].
Adenovirus type 5 was the most common isolate; types 1 and 2 also were identified. Six of
14 patients (43 percent) died; four recovered with a decrease in immunosuppressive
therapy, while four other survivors required retransplantation. In another study,
examination of pre- and posttransplant sera from recipients and donors suggested that
latent virus was transmitted with the donated organ [15]. Biopsies of small bowel
transplants have also yielded a high incidence of adenovirus isolates. Progression of the
infection and systemic dissemination have been associated with intensive
immunosuppressive therapy [97].

In a study of pediatric cardiac transplant recipients, adenoviruses were implicated as a


cause of graft loss and coronary vasculopathy [98]. Adenovirus was detected by
polymerase chain reaction in myocardial biopsies from 24 of 149 patients (16 percent) and
was associated with reduced graft survival.

Congenital immunodeficiency syndromes Primary adenoviral infections can cause


severe disease that is frequently fatal in children with immunodeficiency syndromes, such
as severe combined immunodeficiency disease (SCID). In patients with SCID, subgroup A
type 31 and several subgroup B and C types have been associated with fatal pneumonia
and hepatitis [67,99].

Neonates Adenovirus can cause fatal disseminated neonatal infections. In a review of


adenovirus disease in 26 neonates requiring hospitalization, respiratory signs and
temperature instability were the most common presenting features [100]. Only one
neonate was premature (34 weeks), and one had congenital heart disease. Five neonates
(19 percent) had disseminated disease; the mean age of onset was seven days, and
mortality was 80 percent. In contrast, 21 neonates with localized disease had a mean day
of onset of 18 days and none died.

AIDS A number of unusual adenovirus serotypes have been isolated from HIV-infected
patients. The most common urine isolates are subgroup B types 11, 34, and 35, with
several intermediate strains [101,102]. The subgroup D adenoviruses are the predominant
isolates from stool samples, including eight new serotypes, 43 through 49 and 51
[102,103].

Despite the frequency with which they are found in stool or urine specimens, adenoviruses
are an uncommon cause of morbidity or mortality in HIV-infected patients. The viruses
have been documented by histopathology or electron microscopy in colonic biopsies in
some patients with chronic diarrhea [104]. However, the diarrhea may improve with
treatment of other pathogens.

Fatal cases of adenovirus infection in AIDS patients have been reported. For example,
fatal hepatic necrosis has been documented in pediatric AIDS patients due to adenovirus
types 1, 2, and 5 [105]. In the same review, a case of fatal adenovirus type 3 pneumonia
complicated by hepatitis and encephalitis was described in an adult AIDS patient. Other
reports include cases of adenoviral encephalitis [106] and necrotizing tubulointerstitial
nephritis [107].

POSSIBLE ASSOCIATION WITH OBESITY In a cross-sectional study of 124 children


and adolescents aged 8 to 18 years, antibodies to the subgroup D adenovirus type 36
were found in 19 individuals [108]. Fifteen (78 percent) of the 19 seropositive individuals
were obese (body mass index [BMI] 95th percentile), and antibodies against adenovirus
36 were found significantly more frequently among obese individuals than nonobese
individuals (22 versus 7 percent). Among the obese children, those who were seropositive
for adenovirus type 36 had a higher weight, BMI, waist circumference, and waist-height
ratio than those who were seronegative. Although these results suggest a possible link
between adenovirus type 36 seropositivity and obesity, they do not establish a causal
relationship. In contrast, in a study of 500 military recruits in which 21 percent had
antibodies to adenovirus type 36 detected by enzyme-linked immunosorbent assay, there
was no difference in BMI between seropositive and seronegative individuals [109].

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, The Basics and Beyond the Basics. The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)

Basics topic (see "Patient education: Adenovirus infections (The Basics)")

SUMMARY

Adenoviruses are a family of viruses that are an important cause of febrile illnesses
in young children. They are most frequently associated with upper respiratory tract
syndromes, such as pharyngitis or coryza, but can also cause pneumonia. Less
commonly, adenoviruses cause gastrointestinal, ophthalmologic, genitourinary, and
neurologic diseases. Most adenoviral diseases are self-limiting, although fatal
infections can occur in immunocompromised hosts and occasionally in healthy
children and adults. (See 'Introduction' above and 'Clinical presentation' above.)
Adenoviruses have a double-stranded DNA genome of approximately 35 kb
surrounded by a nonenveloped icosahedron with fiber-like projections. (See 'Virion
structure' above.)
Adenoviruses have a worldwide distribution, and infections occur throughout the
year. Most individuals have serologic evidence of prior adenoviral infection by the age
of 10. Adenovirus infections are prevalent in daycare centers and in households with
young children. (See 'Epidemiology' above.)
Many epidemics of adenoviral disease have been described, including
pharyngoconjunctival fever in summer camps and in association with public
swimming pools, keratoconjunctivitis in medical facilities, and serious acute
respiratory disease in military recruits. (See 'Epidemiology' above.)
Over 50 human adenovirus serotypes have been identified based upon antigenic
determinants detected by viral neutralization assay. Serotypes are further classified
into six subgroups, A to F. Serotypes within each subgroup frequently share similar
biologic properties. As examples, subgroup B types 11, 34, and 35 cause
hemorrhagic cystitis, whereas subgroup D types 8, 19, and 37 are associated with
keratoconjunctivitis (table 1). (See 'Overview' above.)
Adenovirus 14 is a subgroup B serotype that was first identified in military recruits in
the Netherlands in 1955. It subsequently emerged in the United States in 2005 as a
cause of outbreaks of severe respiratory illness in military recruits and civilians.
(See 'Adenovirus 14' above.)
The clinical manifestations of adenoviral disease vary according to the age and
immunocompetence of the host (table 2). Severe disease has been associated
primarily with subgroups B and C serotypes. (See 'Clinical presentation' above.)
A wide range of clinical syndromes has been reported in hematopoietic cell
transplant (HCT) recipients, including pneumonia, colitis, hepatitis, hemorrhagic
cystitis, tubulointerstitial nephritis, encephalitis, and disseminated disease.
(See 'Hematopoietic cell transplantation' above.)
In contrast to the HCT population, adenoviral disease typically involves the donor
organ in solid organ transplant recipients. (See 'Solid organ transplantation' above.)

Diagnosis, treatment, and prevention of adenovirus infection

Authors:
Flor M Munoz, MD, MSc
Phyllis Flomenberg, MD
Section Editors:
Martin S Hirsch, MD
Morven S Edwards, MD
Deputy Editors:
Anna R Thorner, MD
Mary M Torchia, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Apr 15, 2016.

INTRODUCTION Adenoviruses are a family of DNA viruses that are an important cause
of febrile illnesses in young children. They are most frequently associated with upper
respiratory tract syndromes such as pharyngitis or coryza but can also cause pneumonia.
Less commonly, adenoviruses cause gastrointestinal, ophthalmologic, genitourinary,
neurologic, and disseminated disease. Most adenoviral diseases are self-limiting, although
fatal infections can occur in immunocompromised hosts and occasionally in healthy
children and adults.

The available diagnostic tests and strategies for treatment and prevention of adenovirus
infection will be reviewed here. The virology, epidemiology, and clinical manifestations of
adenovirus infection are discussed separately. (See "Epidemiology and clinical
manifestations of adenovirus infection".)

OVERVIEW Since adenoviruses are associated with a variety of clinical syndromes and
nonspecific manifestations, diagnosis based upon clinical criteria alone is challenging. The
diagnosis of adenovirus disease should be confirmed in outbreaks of infection and in
individual patients with serious disease manifestations. Confirmation of adenovirus
infection is important in order to decide on the use of antiviral agents, exclude other
treatable infections, establish a prognosis, and initiate infection control measures when
appropriate.

DIAGNOSTIC TESTS A number of different approaches are available for the specific
diagnosis of adenovirus infection (table 1). Viral culture, adenovirus-specific viral antigen
assays, and polymerase chain reaction (PCR) assays are used most frequently.

Viral culture All adenovirus serotypes except types 40 and 41 cause a characteristic
cytopathic effect (CPE) in human epithelial cell lines such as HeLa, A549, or HEp2 and in
primary human embryonic kidney (HEK) cells. CPE generally occurs within 2 to 7 days
with the common lower serotypes, but some others, especially subgroup D serotypes
(which cause epidemic keratoconjunctivitis), can require up to 28 days.

Adenoviruses are relatively stable and can be readily recovered from clinical samples early
in the course of the disease. Appropriate samples include nasopharyngeal swabs or
aspirates, throat swabs or washes, sputum, tracheal aspirates, bronchoalveolar lavage
(BAL) fluid, conjunctival swabs or scrapings, stool or rectal swabs, urine, blood,
cerebrospinal fluid (CSF), and tissue samples. Swabs and tissue biopsies should be
placed in a viral transport medium to prevent drying and to inhibit bacterial overgrowth.
Specimens should be transported to the laboratory on ice. The duration of viral excretion at
the time of acute disease is approximately one to three days from throat in adults with
upper respiratory infection; three to five days from nose, throat, and eye in patients with
pharyngoconjunctival fever; and two weeks from eye cultures in patients with
keratoconjunctivitis. Viral excretion may be prolonged (for weeks) in young children [1-4].

After acute infection, adenoviruses may be intermittently excreted in stool (or upper
respiratory tract, less commonly) for months in some patients. In immunocompromised
hosts, adenoviruses may be continuously shed from stool or urine for months without
symptoms. Therefore, a positive culture result needs to be interpreted based upon the
current clinical manifestations. (See "Epidemiology and clinical manifestations of
adenovirus infection".)

Viral antigen assay Direct detection of adenovirus antigens in clinical samples may be
performed by an adenovirus-specific enzyme immunoassay (EIA) or immunofluorescence
assay. These assays are more rapid but less sensitive than viral culture for the detection of
most serotypes [5]. They are insufficiently sensitive for diagnosis in immunocompromised
hosts [6].

Commercially available assays use adenovirus-specific monoclonal antibodies that react


with common antigenic determinants on all serotypes. In particular, antigen assays are the
test of choice for the detection of the fastidious adenovirus types 40 and 41 in stool
samples [7]. These enteric adenoviruses are an important cause of diarrhea in infants.

Another potential application for direct antigen assays is in the rapid diagnosis of epidemic
keratoconjunctivitis (EKC). The Adenoclone-EIA (Cambridge Biotech) was evaluated as a
rapid diagnostic test for adenoviral ocular infection applied to conjunctival swabs from 372
culture-positive infected eyes [8]. The overall sensitivity of the EIA was only 38 percent,
but, in swabs obtained within the first week of illness, the sensitivity improved to 65
percent. Therefore, this assay may be a useful adjunct to routine viral culture early in the
course of the illness.

Direct adenovirus antigen assays can also be used to screen cell cultures before the
development of CPE, as well as to confirm the presence of adenovirus in cell cultures
positive for CPE.

Polymerase chain reactions PCR is a highly sensitive and specific assay that can be
used to detect adenovirus DNA from a variety of clinical specimens including fixed tissues.
PCR is particularly helpful in samples from normally sterile sites such as blood, CSF, and
tissues. A positive result from upper respiratory tract or stool samples is more difficult to
interpret as it may represent virus shedding rather than symptomatic infection. Therefore,
PCR results must be interpreted in the context of the clinical findings of adenovirus
disease. Because different adenovirus serotypes are heterogeneous at the DNA level,
PCR primers may be selected to detect specific serotypes or related serotypes [9].
Commercial adenovirus PCR assays use universal primers and probes that detect most or
all serotypes [10,11].

Detection of adenovirus DNA in the blood by quantitative PCR is increasingly utilized for
the evaluation of adenovirus infections in immunocompromised patients [10,12]. Studies
have demonstrated an association between rising or high-level viremia and the risk of both
invasive disease and mortality [13,14]. In addition, quantification of adenovirus DNA can
be used to assess response to antiviral treatment [15-18]. In one study, a greater than 10-
fold decrease in viral load one week after the first dose of antiviral therapy was associated
with a favorable clinical course, whereas all patients with fatal disease failed to show a
significant reduction in viral load [15]. PCR can also be used in conjunction with
sequencing in order to rapidly genotype adenovirus isolates [19]. (See 'Serotyping and
genotyping' below.)

PCR has been used to diagnose adenovirus myocarditis. Routine viral cultures and
histopathology are rarely positive in cases of presumed viral myocarditis. In one study, 38
myocardial tissue samples from 34 patients with acute myocarditis and 17 control patients
with congenital heart disease or hypertrophic cardiomyopathy were tested by PCR for
adenovirus and enterovirus [20]. Although enteroviruses have been implicated as the
major etiology of viral myocarditis, adenovirus DNA was detected more commonly (15
samples) than enterovirus DNA (8 samples). All control samples were negative. In another
report, PCR was used to make a diagnosis of intrauterine adenovirus myocarditis [21].
(See "Etiology and pathogenesis of myocarditis", section on 'Adenovirus' and "Clinical
manifestations and diagnosis of myocarditis in adults", section on 'Identifying the cause of
myocarditis' and "Clinical manifestations and diagnosis of myocarditis in children", section
on 'Endomyocardial biopsy'.)

In addition, detection of adenovirus by PCR in heart biopsies of cardiac transplant


recipients may correlate with increased graft loss [22].

Histopathologic studies Definitive diagnosis of adenovirus disease may require tissue


biopsy. Specimens should be obtained for both pathology and viral culture or PCR
because routine histopathology may be nonspecific, especially in the early stages of
infections.

Adenoviruses can cause characteristic intranuclear inclusions (picture 1) [23]. Early post-
infection, cells may display small eosinophilic inclusions. During the later stages of
infection, basophilic inclusions appear, which initially may be surrounded by a clear halo
within the nucleus. When these intranuclear inclusions enlarge and obscure the nuclear
membrane, the cells are referred to as "smudge" cells (picture 1). Occasionally, adenovirus
inclusions may be confused with cytomegalovirus (CMV) inclusions, but, unlike CMV,
adenoviruses cause neither intracytoplasmic inclusions nor multinucleated cells [24].

If routine histopathology is non-diagnostic and viral culture of tissue is negative (or not
done), more specialized tests may be performed on tissue samples. Electron microscopy
can be used to detect the characteristic icosahedral virions that typically form large
paracrystalline aggregates with the nuclei of infected cells [25]. Adenovirus-specific
immunohistochemical assays and in situ DNA assays are also available [26,27].

Serology Recent infection may be documented by assay of paired acute and


convalescent sera for adenovirus-specific antibodies [28]. It is important to document a
fourfold or greater rise in antibody titer because there is a high prevalence of anti-
adenovirus antibodies in the general population, and there are numerous cross-reactions
between related serotypes.

Commercially available EIAs and complement fixation assays measure adenovirus-


specific anti-hexon antibodies but do not provide information about the serotype. In
contrast, detection of hemagglutination inhibition antibodies or neutralizing antibodies is
more sensitive and is serotype specific. These assays are primarily performed in reference
laboratories and are best interpreted when the patient's sera is tested against the patient's
own isolate.

Serotyping and genotyping After recovery of a clinical isolate on tissue culture, further
evaluation can be performed by serotype analysis in a reference virology laboratory.
Certain serotypes are associated with distinct clinical manifestations (table 2).
(See "Epidemiology and clinical manifestations of adenovirus infection".)

The serotype is determined by first grouping the isolate by hemagglutination pattern with
rat and rhesus red blood cells. Then, hemagglutination inhibition and/or serum
neutralization assays can be performed using a selected panel of type-specific sera.
Genotyping can also be accomplished by PCR and sequencing, which is substantially
faster than the traditional serotyping methods, although it is not widely available.
(See 'Polymerase chain reactions' above.)

Restriction endonuclease analysis Restriction endonuclease (RE) analysis can


distinguish between different clinical isolates of the same serotype. RE analysis is useful
for epidemiologic analysis (eg, during outbreaks of adenovirus infection). As an example,
RE was used to analyze isolates obtained during an outbreak of EKC caused by
adenovirus serotype 8 [29]. In this epidemic, cases occurred simultaneously in two
childcare centers, followed by prolonged outbreaks within the community and among staff
at the local hospital. RE analysis of the genomes of five isolates revealed they were
identical and distinct from the prototype adenovirus serotype 8, supporting the conclusion
that the cases in the larger outbreak were connected.

DIAGNOSTIC TESTS OF CHOICE FOR DIFFERENT ADENOVIRUS


SYNDROMES The diagnostic test of choice varies depending upon the clinical scenario
(table 3).

Upper respiratory illness Adenoviruses should be suspected as one of the causes of


febrile illnesses with respiratory symptoms in infants and young children. Adenoviruses are
a common cause of tonsillitis in young children. Conjunctivitis accompanied by pharyngeal
symptoms, known as pharyngoconjunctival fever, is a characteristic, though less frequent,
adenovirus syndrome. Adenoviruses are also implicated in outbreaks of febrile respiratory
disease in summer camps and swimming pools. (See "Epidemiology and clinical
manifestations of adenovirus infection", section on 'Respiratory tract'.)

When warranted, such as during an epidemic, diagnosis can be confirmed by viral culture
of the nasopharynx or throat. If viral culture is unavailable, the specimen may be tested
with the less sensitive adenovirus-specific enzyme-linked immunosorbent assay (ELISA).

The differential diagnosis includes:

Rhinovirus (see "Epidemiology, clinical manifestations, and pathogenesis of


rhinovirus infections")
Influenza (see "Diagnosis of seasonal influenza in adults" and "Seasonal influenza
in children: Clinical features and diagnosis", section on 'Whom to test')
Respiratory syncytial virus (see "Respiratory syncytial virus infection: Clinical
features and diagnosis", section on 'Laboratory diagnosis')
Parainfluenza (see "Parainfluenza viruses in children", section on
'Diagnosis' and "Parainfluenza viruses in adults", section on 'Diagnosis')

Epidemic keratoconjunctivitis Adenoviruses are the most common cause of epidemic


keratoconjunctivitis (EKC), a syndrome characterized by eye pain and inflammation, fever,
and preauricular lymphadenopathy. EKC is highly contagious and often occurs in
outbreaks. It is best to obtain conjunctival swabs for both viral culture and adenovirus-
specific ELISA or polymerase chain reaction (PCR) assay to make a diagnosis of EKC,
since subgroup D isolates, which are frequently implicated, can take two to four weeks to
grow in tissue culture.

The differential diagnosis includes bacterial conjunctivitis as well as other viral pathogens
such as enteroviruses and herpes simplex virus. (See "Conjunctivitis", section on 'Bacterial
conjunctivitis' and "Clinical manifestations and diagnosis of enterovirus and parechovirus
infections", section on 'Ocular infections' and "Clinical manifestations and diagnosis of
herpes simplex virus type 1 infection", section on 'Keratitis'.)

Pneumonia Adenoviruses are an important etiology of fever and interstitial pulmonary


infiltrates in infants and children. Although uncommon in adults, there have been well-
described outbreaks of adenovirus pneumonia among military recruits and among adults in
chronic care facilities [30,31]. A diagnosis can be made by viral culture, direct antigen
assay, or PCR assay on a nasopharyngeal aspirate or swab, throat swab, sputum sample,
or bronchoalveolar lavage fluid.

Multiplex PCR assays that detect a panel of respiratory viruses including adenovirus from
nasopharyngeal specimens are especially useful for evaluation of hospitalized patients
with suspected respiratory viral pneumonia or other influenza-like illness [32,33]. However,
in a prospective study that compared the prevalence of viruses in the upper respiratory
tracts of children and adults with community-acquired pneumonia with the prevalence in
asymptomatic controls, detection of adenovirus was associated with pneumonia only in
children <2 years of age [34]. This suggests that adenovirus may not be the causative
pathogen of pneumonia in all patients in whom it is detected (especially in those 2 years
of age).

The differential diagnosis includes:

Respiratory syncytial virus (see "Respiratory syncytial virus infection: Clinical


features and diagnosis", section on 'Laboratory diagnosis')
Influenza (see "Diagnosis of seasonal influenza in adults", section on 'Approach to
diagnosis' and "Seasonal influenza in children: Clinical features and diagnosis",
section on 'Whom to test')
Parainfluenza (see "Parainfluenza viruses in adults", section on
'Diagnosis' and "Parainfluenza viruses in children", section on 'Diagnosis')
Human metapneumovirus (see "Human metapneumovirus infections", section on
'Clinical manifestations')

Diarrhea in young children Although norovirus is the more common pathogen, enteric
adenoviruses (types 40 or 41) can cause a prolonged diarrheal syndrome in infants,
especially in the setting of clusters (eg, in daycare centers or as a healthcare-associated
infection). The test of choice is an adenovirus-specific PCR or ELISA on a stool specimen
because enteric adenoviruses do not grow on routine tissue culture. Symptoms are self-
limited and treatment is supportive. Strict infection control methods in daycare centers may
help to prevent transmission.

Infections in immunocompromised hosts Adenoviruses cause a wide range of


clinical syndromes in immunocompromised hosts, including pneumonia, hemorrhagic
cystitis, nephritis, colitis, hepatitis, encephalitis, and disseminated disease. Adenovirus
infections commonly occur in immunocompromised children resulting from either
reactivation of latent infection or primary infection. Because adenoviruses may be shed
asymptomatically in throat, stool, or urine, it is often necessary to obtain tissue to diagnose
some types of disease. (See "Epidemiology and clinical manifestations of adenovirus
infection", section on 'Infections in immunocompromised hosts'.)

Adenoviruses may cause severe, sometimes fatal, disease in hematopoietic stem cell
transplant recipients. After hematopoietic stem cell transplantation, recovery of T cell
function and adenovirus-specific T cells has been associated with a favorable outcome
[35,36]. Recipients of T cell-depleted grafts or those with graft-versus-host disease
(GVHD) are at highest risk for disease and mortality. (See "Overview of infections following
hematopoietic cell transplantation".)

The specific diagnosis of adenovirus infection in immunocompromised patients may


require the use of multiple diagnostic modalities on various specimens. PCR, viral culture,
or direct antigen assays of upper nasopharyngeal, throat, urine, and stool or rectal
samples will detect viral shedding. Results should be interpreted in the context of clinical
manifestations consistent with adenovirus infection. In addition, testing of blood and
affected sites (including lower respiratory tract secretions collected by tracheal aspirate or
bronchoalveolar lavage in patients with pneumonia; urine in patients with hemorrhagic
cystitis; cerebrospinal fluid in patients with central nervous system involvement; and tissue
biopsy in patients with pneumonia, colitis, nephritis, or hepatitis) may be needed to
diagnose adenovirus infection. Quantitative PCR of blood is helpful to establish a
diagnosis, evaluate risk for dissemination and prognosis, and monitor response to antiviral
therapy [14-18,37].
As has been shown for cytomegalovirus (CMV) infections, early identification of patients at
risk for adenovirus disease by monitoring for viremia by PCR is beneficial; thus, some
centers have adopted routine weekly surveillance measures for pediatric recipients of
allogeneic hematopoietic stem cell transplants [14,38-40]. If viremia is detected, then
patients should be carefully evaluated for evidence of disease, such as pneumonia,
hepatitis, cystitis, and colitis, and specimens should be obtained for adenovirus testing
from affected sites. Although viremia is self-limited in some patients, a rising viral load has
been associated with invasive disease [13,14]. In contrast to CMV, the benefit of
preemptive treatment based on viremia alone has not been established for adenovirus and
is not currently recommended because of the toxicity of the most commonly used antiviral
agent, cidofovir. Further clinical studies are also needed to identify effective and safe
treatments. (See 'Treatment' below.)

TREATMENT Most adenovirus infections are self-limited and treatment is supportive.


However, adenovirus infections can be fatal in neonates and immunocompromised hosts
and rarely in healthy children and adults. Given the potential toxicities of the therapy for
adenovirus infections (especially nephrotoxicity with cidofovir), we recommend that an
infectious diseases specialist be consulted when treatment is being considered.

Antiviral agents Antiviral therapy is generally reserved for immunocompromised hosts


and patients with severe adenovirus disease.

There have been no controlled trials demonstrating benefit for any antiviral agent in human
adenoviral disease. The antiviral agent most commonly used for adenoviral infection
is cidofovir, which is currently approved for the treatment of cytomegalovirus (CMV)
infections. (See "Cidofovir: An overview".)

Cidofovir Cidofovir appears more active against adenovirus in vitro than other antiviral
drugs such as ganciclovir [41] and also appears active in vivo as demonstrated by
reductions in adenoviral load measured by real-time polymerase chain reaction (PCR)
[15,16]. Published data on the efficacy of cidofovir for adenovirus infection in humans are
limited to case reports and small nonrandomized studies [15,16,42-45]. In hematopoietic
stem cell and lung transplant recipients, cidofovir therapy has been associated with clinical
improvement and a suggestion of increased survival [16,42-44].

Prior to the use of cidofovir, the mortality in patients with invasive adenoviral disease
following allogeneic hematopoietic cell transplantation (HCT) varied from 25 to 75 percent
in different series [46,47], with the higher rates being described in patients with pneumonia
and disseminated disease [16,47,48]. In contrast, the mortality rate from adenoviral
disease was only 19 percent in a review of 70 published cases of definite or probable
adenovirus infection treated with two or more doses of cidofovir; most of these patients
were severely immunocompromised (eg, graft-versus-host disease and/or T cell-depleted
allografts) [16]. However, in a report of 11 severely immunocompromised patients with
adenovirus infection who were treated with cidofovir, five died, including all three with
pneumonia [49]. Therefore, although early diagnosis and treatment of adenovirus
infections in this patient population may improve outcomes, lymphocyte reconstitution also
appears crucial for recovery from disease [50].

Nephrotoxicity is a major dose-limiting factor for cidofovir. As a result, doses of


1 mg/kg every other day or three times per week instead of the standard treatment dose of
5 mg/kg weekly have been used in an attempt to reduce this toxicity [44]. Further clinical
studies are needed to assess the efficacy and the nephrotoxicity of cidofovir in various
dosing schedules. (See "Cidofovir: An overview".)

Lipid-ester derivatives of cidofovir Experimental oral lipid-ester derivatives


of cidofovir exhibit enhanced in vitro activity against adenoviruses [51] and have lower
potential for nephrotoxicity than cidofovir [52]. In a report of therapy with an oral cidofovir
prodrug, brincidofovir (CMX001), in 13 immunocompromised patients (including 11
allogeneic HCT recipients), 9 of 13 demonstrated a virologic response [53]. Patients with a
virologic response had longer survival than those without a virologic response (median 196
days versus 55 days). No serious adverse events were attributed to the drug. Brincidofovir
is currently undergoing evaluation for the treatment of adenovirus infection in a phase III
open-label study [54].

Other Ganciclovir has limited activity against adenovirus in vitro [55] and in a hamster
model [56]. Neither ribavirin nor vidarabine has consistent activity against adenovirus in
vitro [57]. There are case reports of patients responding to treatment with each of these
agents, but the evidence for efficacy in vivo remains anecdotal [58-60].

Immunotherapy Hypogammaglobulinemia has been associated with severe


adenovirus infections [61]. There is some evidence for the use of immunotherapy in the
treatment of adenovirus disease in immunocompromised patients. Pooled
intravenous immune globulin (IVIG) contains high levels of neutralizing antibodies against
common lower adenoviral serotypes [62] and is commonly used as adjunctive therapy in
immunocompromised patients [16,36]. In one case, a child with severe combined
immunodeficiency (SCID) and a severe adenovirus serotype 7 pneumonia responded
rapidly to therapy with high-dose IVIG containing a high titer of neutralizing antibody
against serotype 7 [63]. In a murine model of mouse adenovirus infection, passive transfer
of adenovirus-specific IgG resulted in a marked delay in mortality [64].

T cell immunity is critical for recovery from adenovirus infection following hematopoietic
stem cell transplantation [65]. Pilot studies of adoptive transfer of T cell immunity have
been performed in children with adenovirus infection after stem cell transplantation. In one
study, virus-specific donor T cells were isolated and infused into nine children with
systemic adenovirus infection [66]. In vivo expansion of adenovirus-specific T cells was
demonstrated and viral clearance was attained in five of six evaluable patients. In one
patient, adoptive T cell transfer led to exacerbation of preexisting graft-versus-host
disease.
In a study of pediatric HCT recipients treated with donor lymphocytes stimulated in vitro
with adenovirus, reductions in viral load were documented in three of three patients with
active infection, and clinical improvement was documented in one patient with adenovirus
pneumonia [67]. In another study, treatment of two haploidentical HCT recipients who had
rising adenovirus loads with donor-derived virus-specific T cells expanded in vitro using
overlapping polypeptides in combination with interleukin-15 resulted in viral clearance in
one and reduction of >1.5 log in viral load in the other [68].

PREVENTION Vaccination and infection control measures have been applied in certain
settings to prevent adenovirus infections.

Vaccination Live oral enteric-coated vaccines directed against adenovirus serotypes 4


and 7 had been used for years in military recruits [69]. They are safe and effective in the
prevention of epidemics of acute respiratory disease in military training camps. In the
1990s, the manufacturer of the vaccines stopped production. Subsequently, new
outbreaks of adenovirus serotypes 4 and 7 disease in training camps occurred, including
several fatalities, underscoring the continued need for the vaccine [70-72]. In addition,
adenovirus serotype 14, a subtype B2 adenovirus, emerged in military recruit training sites
and became the predominant strain. (See "Epidemiology and clinical manifestations of
adenovirus infection", section on 'Adenovirus 14'.)

In 2011, a new live, oral adenovirus vaccine against adenovirus serotypes 4 and 7 was
approved for use in United States military personnel aged 17 through 50 years [73,74].
During the two years following reintroduction of the vaccine, United States military trainees
had a 100-fold decline in adenovirus disease burden (from 5.8 to 0.02 cases per 1000
person-weeks) [75]. There was also a marked decline in the incidence of disease caused
by adenovirus serotypes other than 4 and 7, including adenovirus serotype 14. These data
suggest that the emergence of adenovirus 14 in military recruits during the non-vaccination
period was related to the discontinuation of the adenovirus serotypes 4 and 7 vaccine
program, since heterotypic antibodies to adenovirus 14 develop following adenovirus 7
immunization [72,76,77]. (See "Epidemiology and clinical manifestations of adenovirus
infection", section on 'Adenovirus 14'.)

Infection control Adenoviruses can stay viable for prolonged periods on environmental
surfaces such as sinks and hand towels, and they are not susceptible to some commonly
used disinfectants such as alcohol and ether [78]. Therefore, decontamination of
environmental surfaces and instruments may be difficult and requires specific agents such
as chlorine, formaldehyde, or heat. Outbreaks of pharyngoconjunctival fever from
swimming pool exposure have usually been associated with inadequate water chlorination
[79].

Adenoviruses can cause significant healthcare-associated infections [80-82]. In one report,


126 (7 percent) of 1870 ophthalmology clinic patients developed epidemic
keratoconjunctivitis (EKC) due to adenovirus serotype 8 [80]. Transmission was attributed
to inadequate disinfection of instruments and to finger-to-eye transmission by healthcare
workers. Of note, hand washing did not reliably remove adenoviruses from contaminated
fingers. The recommendations from this study included using gloves to examine patients
with EKC and decontaminating instruments with 10% bleach.

In another report, an epidemic of adenovirus serotype 7 occurred in a neonatal intensive


care nursery resulting in the death of two patients [81]. Symptomatic infection occurred in
9 patients, 10 staff, and 3 parents. The outbreak was controlled by cohorting patients,
using gloves, gowns, and goggles, and excluding symptomatic staff from the unit.

Prolonged infection control measures may be necessary to ensure elimination of


adenovirus following a healthcare-associated outbreak [83]. The Committee on Infectious
Diseases of the American Academy of Pediatrics recommends the following [84]:

For patients with conjunctivitis and for patients with gastroenteritis who are
incontinent or in diapers, contact precautions should be maintained for the duration of
the illness. (See "Infection prevention: Precautions for preventing transmission of
infection", section on 'Contact precautions'.)
For those with respiratory tract infections, contact and droplet precautions are
recommended for the duration of the hospitalization. (See "Infection prevention:
Precautions for preventing transmission of infection", section on 'Contact
precautions' and "Infection prevention: Precautions for preventing transmission of
infection", section on 'Droplet precautions'.)
Disposable gloves and assiduous hand washing should be used when caring for
infected patients.
Healthcare personnel with known or suspected adenoviral conjunctivitis should
avoid direct patient contact for 14 days after the onset of disease in their second eye.

Children who participate in group childcare, particularly during the first two years of life, are
at increased risk for adenoviral respiratory tract infections and gastroenteritis. Specific
preventive measures in this setting have not been established.

INFORMATION FOR PATIENTS UpToDate offers two types of patient education


materials, The Basics and Beyond the Basics. The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)
Basics topic (see "Patient education: Adenovirus infections (The Basics)")

SUMMARY AND RECOMMENDATIONS

Clinical criteria are not sufficient to accurately diagnose adenovirus infection.


Laboratory confirmation of adenovirus infection should be performed if there is
suspicion of this diagnosis and confirmation would be helpful in making decisions
about antiviral therapy, excluding other treatable infections, establishing a prognosis,
and continuing infection control measures when appropriate. (See 'Overview' above.)
Diagnostic tests for adenovirus include viral culture, viral antigen assays
(adenovirus-specific enzyme-linked immunosorbent assay or immunofluorescence
assay), polymerase chain reaction assays, histopathologic studies, and serology
(table 1). (See 'Diagnostic tests' above.)
The diagnostic test of choice varies depending upon the clinical scenario (table 3).
(See 'Diagnostic tests of choice for different adenovirus syndromes' above.)
Most adenovirus infections are self-limited and treatment is supportive. Antiviral
therapy generally is reserved for immunocompromised hosts and patients with severe
disease, but controlled clinical trials have not been performed. (See 'Treatment' above
and 'Antiviral agents' above.)
When treatment is indicated, cidofovir has been the antiviral agent most frequently
used. Nephrotoxicity is a major dose-limiting factor for cidofovir. We recommend
consultation with an infectious diseases specialist when treatment is being
considered. (See 'Treatment' above and 'Cidofovir' above.)
Pooled intravenous immune globulin has been used as adjunctive therapy in
immunocompromised patients, but controlled clinical trials have not been reported.
(See 'Immunotherapy' above.)
Prevention of adenovirus transmission requires decontamination of environmental
surfaces and instruments with agents such as chlorine, formaldehyde, or heat;
adenoviruses are not susceptible to alcohol, ether, or many other commonly used
disinfectants. (See 'Infection control' above.)
Hospitalized patients with gastrointestinal, conjunctival, and respiratory adenovirus
infection should be placed on contact precautions; those with respiratory infection
should also be placed on droplet precautions. (See "Infection prevention: Precautions
for preventing transmission of infection", section on 'Droplet
precautions' and "Infection prevention: Precautions for preventing transmission of
infection", section on 'Contact precautions'.)