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nying documents are a first step toward accomplishing this objective.

ACKNOWLEDGMENTS
We thank the members of the Committee on Infectious Diseases
of the American Academy of Pediatrics and Drs Leah Raye Mabry
and Doug Long for their careful reviews of this document.

REFERENCES
1. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing
among office-based physicians in the United States. JAMA. 1995;273:
214 219
2. Cohen ML. Epidemiology of drug resistance: implications for a postantimicrobial era. Science. 1992;257:1050 1055
3. Barnett ED, Klein JO. The problem of resistant bacteria for the management of acute otitis media. Pediatr Clin North Am. 1995;42:509 517
4. Hofmann J, Cetron MS, Farley MM, et al. The prevalence of drugresistant Streptococcus pneumoniae in Atlanta. N Engl J Med. 1995;333:
481 486
5. Anonymous. Report of the ASM task force on antibiotic resistance.
Antimicrob Agents Chemother. 1995;39(suppl):123
6. Jernigan DB, Cetron MS, Breiman RF. Minimizing the impact of drugresistant Streptococcus pneumoniae (DRSP): a strategy from the DRSP
working group. JAMA. 1996;275:206 209
7. OBrien TF. The global epidemic nature of antimicrobial resistance and
the need to monitor and manage it locally. Clin Infect Dis. 1997;
24(suppl):S2 8
8. McGowan JE Jr. Antimicrobial resistance in hospital organisms and its
relation to antibiotic use. Rev Infect Dis. 1983;5:10331048
9. Reichler MR, Allphin AA, Breiman RF, et al. The spread of multiply
resistant Streptococcus pneumoniae at a day care center in Ohio. J Infect
Dis. 1992;166:1346 1353
10. Dowell SF, Schwartz B. Resistant pneumococci: protecting patients
through judicious use of antibiotics. Am Fam Physician. 1997;55:
16471654
11. Radetsky MS, Istre GR, Johansen TL, et al. Multiply resistant pneumococcus causing meningitis: its epidemiology within a day-care centre.
Lancet. 1981;2:771773
12. Robins-Browne RM, Kharsany ABM, Koornhof HJ. Antibiotic-resistant
pneumococci in hospitalized children. J Hyg. 1984;93:9 16
13. Duchin JS, Breiman RF, Diamond A, et al. High prevalence of multidrug-resistant Streptococcus pneumoniae among children in a rural
Kentucky community. Pediatr Infect Dis J. 1995;14:745750
14. Zenni MK, Cheatham SH, Thompson JM, et al. Streptococcus pneumoniae
colonization in the young child: association with otitis media and resistance to penicillin. J Pediatr. 1995;127:533537
15. Jackson MA, Shelton S, Nelson JD, McCracken GH Jr. Relatively penicillin-resistant pneumococcal infections in pediatric patients. Pediatr
Infect Dis J. 1984;3:129 132
16. Pallares R, Gudiol F, Linares J, et al. Risk factors and response to
antibiotic therapy in adults with bacteremic pneumonia caused by
penicillin-resistant pneumococci. N Engl J Med. 1987;317:18 22
17. Ford KL, Mason EO Jr, Kaplan SL, Lamberth LB, Tillman J. Factors
associated with middle ear isolates of Streptococcus pneumoniae resistant

to penicillin in a childrens hospital. J Pediatr. 1991;119:941944


18. Tan TQ, Mason EO Jr, Kaplan SL. Penicillin-resistant systemic pneumococcal infections in children: a retrospective case control study. Pediatrics. 1993;92:761767
19. Nava JM, Bella F, Garau J, et al. Predictive factors for invasive disease
due to penicillin-resistant Streptococcus pneumoniae: a population-based
study. Clin Infect Dis. 1994;19:884 890
20. Block SL, Harrison CJ, Hedrick JA, et al. Penicillin-resistant Streptococcus
pneumoniae in acute otitis media: risk factors, susceptibility patterns and
antimicrobial management. Pediatr Infect Dis J. 1995;14:751759
21. Moreno F, Crisp C, Jorgensen JH, Patterson JE. The clinical and molecular epidemiology of bacteremias at a university hospital caused by
pneumococci not susceptible to penicillin. J Infect Dis. 1995;172:427 432
22. Brook I, Gober AE. Prophylaxis with amoxicillin or sulfisoxazole for
otitis media: effect on the recovery of penicillin-resistant bacteria from
children. Clin Infect Dis. 1996;22:143145
23. Worrall G, Chaulk P. Hope or experience? Clinical practice guidelines in
family practice. J Fam Pract. 1996;42:353356
24. Paradise JL. Managing otitis media: a time for change. Pediatrics. 1995;
96:712715
25. Goldman DA, Weinstein RA, Wenzel RP, et al. Strategies to prevent and
control the emergence and spread of antimicrobial-resistant microorganisms in hospitals: a challenge to hospital leadership. JAMA. 1996;
275:234 240
26. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical
practice: a systematic review of rigorous evaluations. Lancet. 1993;342:
317322
27. Mainous AG III, Hueston WJ, Clak JR. Antibiotics and upper respiratory infection: do some folks think there is a cure for the common cold?
J Fam Pract. 1996;42:357361
28. Barden LS, Dowell SF, Schwartz B, Lackey C. Current attitudes regarding antibiotic use: results from physicians and parents focus group
discussions. International Conference on Acute Respiratory Infections;
July 1997; Canberra, Australia. Abstract. Page 77
29. Hamm RM, Hicks RJ, Bemben DA. Antibiotics and respiratory
infections: are patients more satisfied when expectations are met? J Fam
Pract. 1996;43:56 62
30. Schwartz B, Bell DM, Hughes JM. Preventing the emergence of antimicrobial resistance: a call for action by clinicians, public health officials,
and parents. JAMA. 1997;278:944 945
31. Fujita K, Murono K, Yoshikawa M, Murai T. Decline of erythromycin
resistance of group A streptococci in Japan. Pediatr Infect Dis J. 1994;13:
10751078
32. Baquero F, Martinez-Beltran J, Loza E. A review of antibiotic resistance
patterns of Streptococcus pneumoniae in Europe. J Antimicrob Chemother.
1991;28(suppl C):3138
33. Arason VA, Kristinsson KG, Sigurdsson JA, Stefansdottir G, Molstad S,
Gudmundsson S. Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross-sectional prevalence
study. Br Med J. 1996;313:387391
34. Boken DJ, Chartrand SA, Goering RV, Kruger R, Harrison CJ. Colonization with penicillin-resistant Streptococcus pneumoniae in a child-care
center. Pediatr Infect Dis J. 1995;14:879 884
35. Stephenson J. Icelandic researchers are showing the way to bring down
rates of antibiotic-resistant bacteria. JAMA. 1996;275:175

Otitis MediaPrinciples of Judicious Use of Antimicrobial Agents


Scott F. Dowell, MD, MPH*; S. Michael Marcy, MD; William R. Phillips, MD, MPH;
Michael A. Gerber, MDi; and Benjamin Schwartz, MD*
From the *Childhood and Respiratory Diseases Branch, National Center for
Infectious Diseases, Centers for Disease Control and Prevention, Atlanta,
Georgia; Kaiser Permanente, Panorama City, California; Northwest Family Medicine, Seattle, Washington; and iConnecticut Childrens Medical
Center, Hartford, Connecticut.
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
PEDIATRICS (ISSN 0031 4005). Copyright 1998 by the American Academy of Pediatrics.

ABSTRACT. Otitis media is the leading indication for


outpatient antimicrobial use in the United States. Overdiagnosis of and unnecessary prescribing for this condition has contributed to the spread of antimicrobial resistance. A critical step in reducing unnecessary prescribing
is to identify the subset of patients who are unlikely to
benefit from antibiotics. Conscientiously distinguishing
acute otitis media (AOM) from otitis media with effusion
(OME), and deferring antibiotics for OME will accom-

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165

plish this goal, and will avoid up to 8 million unnecessary courses of antibiotics annually. Criteria for defining
these conditions are presented, as well as the evidence
supporting deferring antibiotic treatment. Discussions of
shortened courses of antibiotics for AOM and restricted
indications for antimicrobial prophylaxis are also presented. Pediatrics 1998;101:165171; antimicrobial resistance, antimicrobial use, otitis media, upper respiratory
infection, antimicrobial therapy, pediatrics, acute otitis
media, otitis media with effusion, prophylaxis.
ABBREVIATION. AHCPR, Agency for Health Care Policy and
Research.

PRINCIPLES

1. Episodes of otitis media should be classified as


acute otitis media (AOM) or otitis media with
effusion (OME).
2. Antimicrobials are indicated for treatment of
AOM; however, diagnosis requires documented
middle ear effusion and signs or symptoms of
acute local or systemic illness.
3. Uncomplicated AOM may be treated with a 5- to
7-day course of antimicrobials in certain patients.
4. Antimicrobials are not indicated for initial treatment of OME; treatment may be indicated if effusions persist for $3 months.
5. Persistent middle ear effusion (OME) after therapy for AOM is expected and does not require
retreatment.
6. Antimicrobial prophylaxis should be reserved for
control of recurrent AOM, defined by $3 distinct
and well-documented episodes/6 months or $4
episodes/12 months.
BACKGROUND AND JUSTIFICATION

titis media consistently leads the list of the


most common indications for outpatient antimicrobial use in the United States.1 In recent
years, the number of office visits for otitis media has
increased out of proportion to the increase in population size, from 9.9 million visits in 1975 to 24.5
million in 1990. It is not clear why the diagnosis is
being made so much more often, although some
authorities have suggested an association with increased use of out-of-home child care.2
Because of its importance as an indication for antibiotic use, efforts to influence antibiotic prescribing
practices have consistently begun by addressing otitis media. As a result of this emphasis, there is a
considerable body of literature on which recommendations can be based. The relative efficacy of antibiotic treatment for AOM and OME has been welldefined, the natural history of appropriately treated
AOM is understood to include persistent middle ear
effusions for several weeks in the majority of children, and the indications for prophylaxis have been
evaluated. Yet children continue to routinely receive
antimicrobials for OME detected as an incidental
finding, for asymptomatic effusions detected only a
few weeks after an uncomplicated episode of AOM,
and in prophylactic regimens initiated in patients
who have not met strict criteria. More work is
needed to bring current antibiotic prescribing prac166

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tices in line with indications available from the considerable body of recent literature on otitis media.
The following guidelines are intended to begin this
process by highlighting situations in which antibiotic
use may be reduced without compromising patient
care.
EVIDENCE SUPPORTING PRINCIPLES
Episodes of Otitis Media Should Be Classified as AOM
or OME

Distinguishing each episode of otitis media in this


manner leads directly to a management strategy that
optimizes treatment for those children who require
it, but curtails the use of antimicrobials for children
in whom they would not be beneficial. The distinction between these entities is usually clear, but classification of some patients with equivocal otoscopic
findings may require careful clinical judgment.3
AOM is defined as the presence of fluid in the
middle ear in association with signs or symptoms of
acute local or systemic illness. Accompanying signs
and symptoms may be specific for AOM, such as
otalgia or otorrhea; or nonspecific, such as fever.
Antimicrobial agents are indicated for this condition,
as discussed below.
OME is defined as the presence of fluid in the
middle ear in the absence of signs or symptoms of
acute infection. Antimicrobials may be appropriately
deferred for this group of children, in agreement
with recommendations of an expert panel convened
by the US Agency for Health Care Policy and Research (AHCPR).4
Antimicrobials Are Indicated for Treatment of AOM

The cumulative evidence from randomized controlled trials in which antibiotic therapy has been
compared with no therapy for AOM is persuasive in
favoring antibiotic therapy, although the treatment
effect is small.57 Approximately 80% of untreated
children have clinical resolution by 7 to 14 days,
compared with ;95% of those treated with antimicrobials.5 Differences among the various antimicrobials in terms of clinical efficacy, if present, are generally too small to be detected. The benefit of
antimicrobial treatment is most apparent when
pathogenic bacteria are isolated from middle ear
fluid, when bacterial eradication is used to assess
outcome, or when clinical outcome was assessed at 2
to 3 days, rather than 7 to 14 days.6,8 10
Diagnosis of AOM

Although there is general agreement that antimicrobials are indicated for AOM, there is no such
agreement on how to establish the diagnosis. Specific
criteria for the diagnosis have been notoriously difficult to validate or standardize, perhaps reflecting
the diversity of criteria used in practice and in clinical trials. For example, a survey of 165 pediatricians
reported 147 different sets of criteria for the diagnosis of AOM.11 Furthermore, in clinical trials in which
standardization is even more essential, 18 different
sets of criteria were used in 26 trials.11
Agreement can be reached on the essential steps in

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establishing the presence of middle ear effusion,


without which the diagnosis of AOM cannot be supported.4,12 (In rare circumstances, the practitioner
may observe signs of acute inflammation in the
hours before fluid accumulates in the middle ear
cavity.13) Pneumatic otoscopy should be used to assess four principal characteristics of the tympanic
membrane: position, color, translucency, and mobility.14 The use of visual otoscopy alone is discouraged
because of the inability to assess the mobility of the
tympanic membrane.4 Newer diagnostic tools such
as tympanometry and acoustic reflectometry can aid
in establishing the presence of fluid and in validating
the examiners skills through repeated use and comparison with visual observation.
Agreement may be more difficult on which signs
and symptoms of acute local or systemic illness are
sufficient to establish the diagnosis of AOM in conjunction with middle ear effusion. The diagnosis can
be established by the presence of local signs such as
otorrhea with evidence of middle ear origin, a bulging tympanic membrane that has cloudy or yellow
fluid visible behind it or is distinctly red, or local
symptoms such as ear pain.15 Ear-pulling in the absence of other symptoms is not necessarily attributable to AOM.16 Fever may be indicative of AOM,
although in the absence of any other findings, such
as ear pain or a red or bulging tympanic membrane,
fever often may be unrelated to middle ear effusion.17
Other signs and symptoms such as rhinorrhea,
cough, irritability, headache, anorexia, vomiting, or
diarrhea may be present but are not specific for
AOM.18 Although viral upper respiratory infections
frequently precede or accompany AOM, the presence of rhinorrhea or other nonspecific signs or
symptoms of upper respiratory infection alone is not
adequate to differentiate AOM from OME. These
nonspecific symptoms usually reflect an underlying
or preceding viral illness and do not resolve as rapidly after appropriate antibiotic therapy as do fever
and ear pain.19
Uncomplicated AOM May Be Treated With a 5- to
7-Day Course of Antimicrobials in Certain Patients

In the United States, AOM traditionally has been


treated with a 10-day course of antimicrobials. There
are few controlled data to support such a practice,
which seems to have been carried over from the
recommendations for 10 days of penicillin for streptococcal pharyngitis.20 Although physicians prescribe 10-day courses, children often fail to complete
them.21,22
A number of randomized trials have compared
shorter courses of antimicrobial therapy, ranging
from 2 to 7 days, with more traditional courses and
have reported satisfactory results.2327 Most of the
trials were conducted in Europe, where differences
in standard care are such that the results may not be
easily applicable in the United States. One comparison was of 2 days versus 7 days of penicillin V, an
antibiotic not often recommended or used to treat
AOM in the United States.24 Two of the trials enrolled only children .3 years of age, although most
antibiotic failures are reported in those ,18

months.25,26 A trial from the United States reported


no difference in outcome among 59 children who
received 5 days of cefaclor (90% success) compared
with 64 who received 10 days of cefaclor (92% success).27 However, this study, like those cited previously, may not have had the statistical power to
detect a clinically significant difference. A recent trial
including 719 patients reported that the efficacy of 5
days of cefuroxime axetil was equivalent to 10 days
of either cefuroxime or amoxicillin/clavulanate.28
Perhaps more persuasive are reports that a single
dose of ceftriaxone, which produces therapeutic middle ear concentrations of antibiotic for only 3 to 5
days, is equally effective as a 10-day course of amoxicillin or trimethoprim-sulfamethoxazole.20,29 In any
case, although the evidence to support shorter
courses of antimicrobials is not optimal, the evidence
to support 10 to 14 days of antimicrobials is practically nonexistent. In parts of Europe, deferring antibiotic therapy unless symptoms persist for .2 days
or treating with 5 to 7 days of antimicrobials is the
standard of care, and cure rates between 66% and
92% have been recorded among children treated only
with analgesics and observation.6,30 34
Certainly, there are theoretic advantages to decreasing the duration of therapy to 5 to 7 days for
uncomplicated AOM. One would anticipate a reduction in selective pressure favoring resistant organisms, both in the community and in the individual
patient. In fact, shorter courses may reflect more
realistically the actual dispensing practices of parents
and make it more likely that the medications are
given as prescribed.
Although the available data support the use of
short-course therapy for older children with mild
AOM, such treatment has not been well-evaluated in
children with severe or complicated AOM. Ten or
more days of antimicrobials may be necessary for
those children who present with perforation of the
tympanic membrane.27 In addition, the trials assessing efficacy of shorter courses generally excluded
patients at higher risk for treatment failure, such as
those with underlying medical conditions and those
with chronic or recurrent otitis media.35 Data supporting short courses of therapy in such patients are
therefore lacking, and short-course therapy for these
patients cannot be recommended until more data
become available.
Short-course therapy also may not be appropriate
for younger children. Children ,15 months to 2
years of age are at increased risk for treatment failure, even with conventional dosing.3537 The eight
trials of short-course therapy reviewed above enrolled ;250 children ,18 months of age, but most
did not analyze the success of therapy separately for
this group. Recently, a randomized trial comparing 5
days with 10 days of amoxicillin/clavulanate documented significant differences favoring the 10-day
regimen among children ,2 years of age.38 In the
absence of additional data testing the efficacy of
short course treatment in this age group, it seems
prudent to restrict short-course therapy to children
.2 years of age.

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167

Antimicrobials Are Not Indicated for Initial Treatment


of OME

Recent comprehensive reviews of the literature


have been conducted and an expert panel of the US
AHCPR has addressed the issue of antibiotic treatment for OME. Results of these analyses indicate that
in the majority of cases, antimicrobial therapy can be
deferred safely while OME resolves spontaneously,
and that antimicrobials are effective at resolving effusion in only a minority of cases.
Three metaanalyses of published trials of antibiotic
therapy for OME have concluded that there is a small
but statistically significant effect on short-term resolution.4,39,40 Most of these trials enrolled children with
documented middle ear effusion but no recent history of AOM. No beneficial effect of therapy was
seen in those studies that included children with
illnesses characterized by a high natural cure rate,
such as children with effusion after a recent episode
of AOM.39 Approximately 65% of all cases of OME
will resolve within 3 months without antibiotic therapy,41 as will 90% of the subset of OME that immediately follows a diagnosed episode of AOM. Although the overall difference in the rate of short-term
resolution between treated and untreated children in
the metaanalyses was statistically significant, about
seven children would have to be treated with antimicrobials for one to benefit.8 Of greater importance,
however, is that there was no significant difference in
the incidence of OME when assessed .1 month after
treatment was completed, whether placebo or antibiotic therapy was used.40 These findings have
prompted many experts to recommend that middle
ear effusion in the absence of AOM should not be
treated with antimicrobials at all.42
Guidelines for the diagnosis and treatment of
OME have been published recently by an expert
panel convened by the US AHCPR and endorsed by
the American Academy of Pediatrics, the American
Academy of Family Physicians, and the American
Academy of OtolaryngologyHead and Neck Surgery.4 For initial treatment of OME, the panel endorsed either of two options with similar long-term
outcomes: observation with no therapy or antibiotic
therapy.
With the accumulation of evidence that antibiotic
use increases the risk for both colonization and invasive disease with penicillin-resistant Streptococcus
pneumoniae,43 observation without antibiotic therapy
now appears to be the preferred option. For the
practicing physician faced with a well-appearing
child with a middle ear effusion, considerations of
risks and benefits to that individual child appropriately outweigh concerns about the emergence of antimicrobial resistance in the community as a whole.
Thus, the observation that children treated with a
course of antimicrobials are at increased risk to become carriers of nonsusceptible pneumococci as a
result of that treatment,44 and that carriers of resistant strains are more likely to fail antibiotic therapy,45
must take precedence over the sometimes marginal
benefits of antibiotic therapy for that child.
The AHCPR guidelines recommend antibiotic
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therapy or bilateral myringotomy with insertion of


tympanotomy tubes for patients in whom bilateral
effusion has been documented to persist for 3
months and is accompanied by significant bilateral
hearing loss. This approach is reasonable, because
persistent middle ear effusions in infancy have been
associated in some studies with deficits in cognitive
function and school achievement at age 7 years,46
although this has not been a consistent finding,4 and
recent evidence indicates that cognitive deficits, if
present, may be related more to diminished maternal
responsiveness secondary to the hearing loss than to
the hearing loss per se.47,48
The AHCPR panel defined a patient with OME as
a child between 1 and 3 years of age with effusion
present 6 weeks after an acute episode of otitis media, with no apparent symptoms, and with no underlying medical condition. The panel estimated that
25% to 35% of all diagnoses of otitis media would fit
the criteria of OME.4 Were antimicrobials deferred
for this group of children alone, 6 to 8 million courses
of unnecessary antibiotic therapy could be avoided
each year.
Persistent Middle Ear Effusion After Therapy for AOM
Is Expected and Does Not Require Retreatment

The natural history of appropriately treated AOM


is for middle ear effusion to persist for weeks to
months, a fact that may not be recognized clearly by
physicians who reexamine ears soon after therapy is
completed. Approximately 70% of children will have
fluid in the middle ear at 2 weeks, 50% at 1 month,
20% at 2 months, and 10% at 3 months, despite
appropriate antibiotic therapy.14,42,49 Thus, when middle ear fluid is detected in asymptomatic children at
follow-up visits for AOM, administering additional
courses of antimicrobials is generally unnecessary.50
An important step in reducing the burden of unnecessary antibiotic treatment for otitis media is the
recognition that persistent effusions are part of
the expected course of AOM and do not warrant
therapy.
It may appear difficult to distinguish the child who
has a persistent middle ear effusion as part of the
natural course of appropriately treated AOM from
the child who has a new effusion as part of a second
episode of acute disease, but this distinction can be
made by using the same criteria listed above to distinguish AOM from OME. When the effusion is accompanied by new onset of local or systemic signs or
symptoms of infection, such as fever or persistent ear
pain, AOM is diagnosed and a course of antimicrobials is administered. On the other hand, middle ear
effusion in a child who has had an episode of AOM
in the previous 2 to 3 months and in whom signs of
acute illness are absent or nonspecific, such as rhinorrhea alone, would not warrant a second course of
antimicrobials. Irrespective of the recent history of
middle ear disease, the administration of a course of
antimicrobials should be recommended only for
those children with both middle ear effusion and
new onset of local or systemic illness, or with bilateral effusions accompanied by documented hearing
loss for $3 months, as discussed above.

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Antibiotic Prophylaxis Should Be Reserved for Control


of Recurrent AOM

The efficacy of continuous prophylactic antimicrobials for the control of recurrent AOM is well-established, although the decrease in frequency of recurrent episodes is small.40 Nevertheless, because of the
potential consequences of emergence of additional
resistant pneumococci, a recommendation that antibiotic prophylaxis for AOM be avoided whenever
possible has been made.12 Others have argued that
prophylaxis remains a valuable therapeutic option
for children with recurrent AOM and should not be
dismissed so readily.51
Trials in which children treated with daily low-dose
antibiotic therapy were compared with those given
placebo have consistently documented a lower incidence of AOM in the treated group, whether the antibiotic used was erythromycin,52 amoxicillin,53,54 trimethoprim-sulfamethoxazole,53,55 or sulfisoxazole.56 61
A metaanalysis summarizing these results concluded
that antibiotic treatment resulted in an average decrease in the number of episodes of AOM of 0.11 episode per patient per month, or slightly more than one
episode per year.40 The treatment effect tended to be
greater when sulfisoxazole was used, when treatment
was continued for ,6 months, or when the population
studied had a high rate of recurrences.40
This last point is important because it indicates
that the type of patient selected for prophylaxis will
determine the utility of the prophylactic regimen.
The benefit of prophylaxis will be greatest if strict
criteria for initiating prophylaxis are used and its use
limited to those who are likely to have frequent
recurrences. The most consistent criterion for prophylaxis in the published trials has been three or
more distinct and well-documented episodes of
AOM in the preceding 6 months or four episodes in
the preceding year. Patients at high risk for severe or
recurrent disease who are most likely to benefit from
prophylaxis include those ,2 years of age, those in
out-of-home child care, and Native American children.51,62 On the other hand, some otherwise eligible
children may be poor candidates for prophylaxis
because of their decreased likelihood of compliance
with the regimen, which was ,50% in one inner-city
population.63
Alternative approaches to antimicrobial prophylaxis for otitis media using different schedules have
been attempted, but none have been as consistently
beneficial as continuous prophylaxis as outlined
above. Intermittent prophylaxis using antimicrobials
administered at the onset of signs of upper respiratory infection was found to be beneficial in preventing recurrent AOM in one study,64 but not another,65
and was significantly less effective than continuous
prophylaxis when the two methods were compared.66 Prophylactic trimethoprim-sulfamethoxazole in conjunction with prednisone after tympanostomy tube insertion decreased the short-term rate
of tube extrusion, but there was no beneficial effect
on the rate of AOM recurrence and no overall longterm benefit.67 An attempt at antibiotic prophylaxis
rather than tympanostomy tube insertion has been

advocated in one study of children with longstanding OME and hearing loss, but surgically
treated patients had a lower rate of treatment
failure and better short-term hearing than those on
prophylaxis.68
The benefit of any form of prophylactic therapy
must be weighed against the risk of promoting antibiotic resistance. Evidence that even short courses of
antimicrobial therapy are associated with an increased risk of nasopharyngeal carriage as well as of
invasive disease with resistant bacteria has been reviewed above and elsewhere.43 In addition, there is
specific evidence that antibiotic prophylaxis increases the likelihood of nasopharyngeal colonization with resistant pneumococci45,69 and the proportion of children with b-lactamase-producing
organisms in middle ear effusions.54,69 This effect is
seen among children given amoxicillin prophylaxis,
but not among those given sulfisoxazole.69 Importantly, the rate of colonization with resistant strains
returned to baseline levels several months after prophylaxis was discontinued.69
Other interventions that may decrease the incidence of recurrent AOM without the risks of antibiotic prophylaxis include eliminating smoking in the
home,70 reducing day care attendance,70 eliminating
pacifiers,71 and giving influenza vaccine.72 Insertion
of tympanostomy tubes has been demonstrated to be
an effective means of reducing the frequency of recurrent AOM and may be a reasonable alternative to
antimicrobial prophylaxis in selected children.73
Conjugate pneumococcal vaccines may provide an
important alternative in the future.74 Parents should
also be reassured that the incidence of recurrent
AOM appears to decrease with increasing age of the
child.75
Control of recurrent AOM among children with
three or more well-documented and separate episodes in the preceding 6 months or four or more
episodes in the preceding 12 months is the only
indication for which evidence of the beneficial effects
of antibiotic prophylaxis has been consistent and
persuasive. Because of the potential consequences of
promoting resistant bacteria to both the patient and
the community, prophylaxis should not be initiated
for other indications. When initiated, the duration of
prophylactic therapy should be no more than 6
months, because longer courses are less effective and
may be more likely to promote colonization with
resistant bacteria.40,76 Either sulfisoxazole or amoxicillin is the agent of choice; cephalosporins have not
been demonstrated to be effective. Sulfisoxazole has
been used in the majority of controlled trials of prophylaxis, appears to be more efficacious at preventing recurrences than the other agents, and may be
less likely than amoxicillin to promote colonization
with b-lactamase-producing bacteria or resistant
pneumococci.
ACKNOWLEDGMENTS
We thank Drs Jerome O. Klein, Jack L. Paradise, Leah Raye
Mabry, and Doug Long and members of the Committee on Infectious Diseases of the American Academy of Pediatrics for their
careful review of this paper.

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214 219
2. Klein JO. Current issues in upper respiratory tract infections in infants
and children: rationale for antibacterial therapy. Pediatr Infect Dis J.
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3. Paradise JL. On classifying otitis media as suppurative or nonsuppurative, with a suggested clinical schema. J Pediatr. 1987;111:948 51
4. Stool SE, Berg AO, Berman S, et al. Otitis media with effusion in young
children. Clinical practice guideline. Agency for Health Care Policy and
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5. Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of antimicrobial
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PharyngitisPrinciples of Judicious Use of Antimicrobial Agents


Benjamin Schwartz, MD*; S. Michael Marcy, MD; William R. Phillips, MD, MPH;
Michael A. Gerber, MDi; and Scott F. Dowell, MD, MPH*
ABSTRACT. Accurate diagnosis of group A streptococcal pharyngitis and appropriate antimicrobial therapy are important, particularly to prevent nonsuppurative sequelae such as rheumatic fever. Most episodes
of sore throat, however, are caused by viral agents.
Clinical findings cannot reliably differentiate streptococcal from viral pharyngitis and most physicians tend
to overestimate the probability of a streptococcal infection based on history and physical examination
alone. Therefore, diagnosis should be based on results
of a throat culture or an antigen-detection test with
throat culture backup. Presumptively starting therapy
pending results of a culture is discouraged because
treatment often continues despite a negative test result. Other bacterial causes of pharyngitis are uncommon and often can be diagnosed based on nonpharyngeal findings. Penicillin remains the drug of choice for
streptococcal pharyngitis because of its effectiveness,
relatively narrow spectrum, and low cost. No group A
streptococci are resistant to b-lactam antibiotics. High
rates of resistance to macrolides has been documented
in several areas; in Finland, decreased national rates of
macrolide use led to a decline in the proportion of

From the *Childhood and Respiratory Diseases Branch, National Centers


for Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia; Kaiser Permanente, Panorama City, California; Northwest Family Medicine, Seattle, Washington; and \Connecticut Children;s
Medical Center, Hartford, Connecticut.
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
PEDIATRICS (ISSN 0031 4005). Copyright 1998 by the American Academy of Pediatrics.

macrolide-resistant group A streptococci. Pediatrics


1998;101:171174; group A Streptococcus, pharyngitis,
diagnosis, antimicrobial therapy.
PRINCIPLES

1. Diagnosis of group A streptococcal pharyngitis


should be made based on results of appropriate
laboratory tests in conjunction with clinical and
epidemiologic findings.
2. Antimicrobial therapy should not be given to a
child with pharyngitis in the absence of diagnosed
group A streptococcal or other bacterial infection.
3. A penicillin remains the drug of choice for treating group A streptococcal pharyngitis.
BACKGROUND AND JUSTIFICATION

ore throat is one of the most common complaints in pediatrics, resulting in millions of
physician office visits each year. Group A Streptococcus (S pyogenes), the leading bacterial cause of
pharyngitis, accounts for ;15% of all cases.1 Diagnosis and treatment of streptococcal pharyngitis are
important because antimicrobial therapy initiated
within 9 days of onset is effective in preventing acute
rheumatic fever.2 In addition, treatment of group A
streptococcal infection may prevent suppurative
complications, lead to more rapid resolution of illness, and prevent the spread of infection. Nevertheless, because most episodes of sore throat are caused

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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and
trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove
Village, Illinois, 60007. Copyright 1998 by the American Academy of Pediatrics. All rights
reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Otitis MediaPrinciples of Judicious Use of Antimicrobial Agents


Scott F. Dowell, S. Michael Marcy, William R. Phillips, Michael A. Gerber and
Benjamin Schwartz
Pediatrics 1998;101;165

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/101/Supplement_1/165.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 1998 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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