Paediatric Respiratory Reviews 15 (2014) 240–245

Contents lists available at ScienceDirect

Paediatric Respiratory Reviews

CME article

Necrotising pneumonia in children

David A. Spencer 1,*, Matthew F. Thomas 2
1
Consultant in Respiratory Paediatrics, Department of Respiratory Paediatrics, Great North Children’s Hospital, Newcastle upon Tyne, NE1 4LP
2
Specialist registrar in Respiratory Paediatrics, Department of Respiratory Paediatrics, Great North Children’s Hospital, Newcastle upon Tyne, NE1 4LP

EDUCATIONAL AIMS

 To describe the pathophysiology of lung necrosis

 To highlight recent changes in pneumococcal and staphylococcal disease and their implications for therapy
 To discuss recent changes in the aetiology and epidemiology of necrotic pneumonia in children
 To provide a practical guide to the management of children with necrotising pneumonia

A R T I C L E I N F O S U M M A R Y

Keywords: Necrotising pneumonia remains an uncommon complication of pneumonia in children but its incidence
Epidemiology
is increasing. Pneumococcal infection is the predominant cause in children but Methicillin resistant
Panton-Valentine Leukocidin
Staphylococcus aureus (MRSA) and Panton-Valentine leukocidin (PVL) staphylococcal infection are also
Pneumococcal vaccination
Respiratory infection important causes of severe necrotising pneumonia. Clinical features of necrotic pneumonia are similar to
those of an uncomplicated pneumonia except that the patient is clinically much more unwell and has
usually failed to respond adequately to what would normally be considered as appropriate antibiotics.
Pleural involvement is frequent. Initial management is similar to that for non-complicated pneumonia
with careful attention to fluid balance and adequate analgesia required. Some patients will need
intensive care support, particularly those with PVL-positive staphylococcal infection. Broad-spectrum
antibiotics should be given intravenously, with the exact choice of agent informed by local resistance
patterns. Pleural drainage is often required. Despite the severity of the illness, outcomes remain excellent
with the majority of children making a full recovery.
ß 2013 Elsevier Ltd. All rights reserved.

INTRODUCTION and Staphylococcus aureus, a list of causative organisms is given in

Necrotizing pneumonia is a severe form of lung disease
associated with the formation of abscesses and cavitation within
the lung parenchyma, and usually, but not always significant
pleural involvement.
AETIOLOGY
Many insults can cause acute lung necrosis, but the great
majority of cases in children are related to infection. Bacterial
infection is the most common, especially Streptococcus pneumoniae
Table 1. Other organisms including Mycoplasma pneumoniae and
adenovirus can cause serious disease with chronic and even fatal
consequences. It should be remembered that infection is frequent-
ly culture negative and modern culture negative techniques may
be required to determine the precise aetiology. This review will
concentrate on infectious causes.
The important non-infectious causes to consider are listed in
Table 2. The most common of these to consider in paediatric
practice is aspiration of food contents, which is frequently
complicated by secondary bacterial infection.
EPIDEMIOLOGY

Necrotising pneumonia is an ancient condition, and previously

* Corresponding author. Department of Respiratory Paediatrics, Great North
Children’s Hospital, Newcastle-Upon-Tyne, NE1 4LP, Tyne & Wear, UK.
Tel.: +44 (0) 191 2825089; fax: +44 (0) 191 222 3082.
E-mail address: David.Spencer2@nuth.nhs.uk (D.A. Spencer).
a major cause of death in both adults and children. The clinical
features may well have first been described by Hippocrates and
later in some detail by Laennec in 1826.1

1526-0542/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.prrv.2013.10.001

Downloaded from ClinicalKey.com at Universidad Autonoma de Guadalajara September 27, 2016.

For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.
 D.A. Spencer, M.F. Thomas / Paediatric Respiratory Reviews 15 (2014) 240–245
Table 1
Infections associated with necrotising pneumonia
Bacterial:
Streptococcus pneumoniae
Staphylococcus aureus
Streptococcus mitis spp.
Streptococcus pyogenes (Group A Streptococcus)
Mycoplasma pneumoniae
Pseudomonas spp.
Fusobacterium spp.
*
A primary fungal cause is very rare in immunocompetent individuals but must be considered in immunosuppressed or immunodeficient patients.
The complications of bacterial pneumonia were major killers of
all age groups prior to the era of antibiotics and modern surgical
techniques. A high proportion of those dying in the great
pandemics of influenza such as that in 1919 will have died from
complications related to the subsequent bacterial pneumonia. As
primary bacterial pneumonia became less common in the 20th
century, so the more severe necrotising forms of the disease also
decreased, at least partially as a consequence of the widespread
introduction of antibiotics.
The problem had become very uncommon in the antibiotic era
but the incidence of complicated disease has again increased over
the last two decades.2 The mechanisms responsible for these
changes vary according to the causative organism, but are complex
and still incompletely understood.
PATHOPHYSIOLOGY
The term necrotising refers to the death of cells or groups of cells
and implies permanent cessation of their integrated function,
although this does not mean that significant clinical and structural
recovery may not occur. Most necrosis in the context of the lung
parenchyma is of the liquifactive or colliquative form. Necrosis by
organisms causing putrefaction results in the production of foul-
smelling gas and brown, green or black discolouration of the tissues
is referred to as gangrene. The term pulmonary gangrene was coined
to describe this type of disease in the 1940s. Hseih et al3 have
emphasised the distinction between necrosis referring to the
pathology whereas gangrene refers to the pathophysiological
mechanism involved, although the terms are often used inter-
changeably in clinical practice.3 This group has also demonstrated
that thrombosis of intrapulmonary blood vessels may well be of
critical importance in mediating the pathophysiology of this group
of conditions.3,4
These changes are additional to the features of lobar pneumonia
which classically are associated with complete clinical and
radiological resolution over time. The consequences of necrosis
are ultimately destruction of the normal lung architecture, which
is replaced by cavities which are surrounded by a wall of variable
Table 2
Important non-infectious causes of necrotising pneumonia
Aspiration of foods contents
Chemotherapeutic agents including Bleomycin, Cyclophospamide
Crohn’s disease
Graft versus host disease
Inhalation of chemicals including hydrocarbons, kerosene, mineral oils,
furniture polish and turpentine
Inhaled foreign body
Meconium aspiration syndrome
Psoriasis
Sickle cell disease
Smoke inhalation
Toxic shock syndrome
Systemic lupus erythematosis
Wegener’s granulomatosis and other necrotising vasculitides
Downloaded from ClinicalKey.com at Universidad Autonoma de Guadalajara September 27, 2016.
For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.
241
Viruses: Fungi*:
Influenza Aspergillus spp.
Adenovirus Candida spp.
Herpes group including -Cytomegalovirus (CMV), Histoplasma capsulatum
Varicella-Zoster, Epstein-Barr Virus (EBV)
Coccidioides spp.
Blastomyces spp.
Cryptococcus neoformans
thickness. The cavity is usually not in continuity with the
conducting airways and is filled with either gas or liquid pus.
Pneumococcal disease
A dramatic increase in paediatric empyema was first reported
from the West Midlands, UK in 19975 and this phenomenon has
since been confirmed by many centres across the globe.6–11
Barriers to understanding the cause or causes of this problem in the
UK have been that most cases are culture negative, presumably
because of antibiotics in primary care and hospital prior to
obtaining pleural fluid for culture, and the fact that blood cultures
are usually negative even in antibiotic naı̈ve patients with invasive
bacterial disease.12 Other countries with presumably higher rates
of positive bacterial culture disease subsequently demonstrated
that most of this disease was pneumococcal in origin.8 This was
then confirmed for culture negative disease with the advent of
pneumococcal PCR and other molecular detection techniques, and
of this most disease was shown to be due to serotype 1 disease
using serotype specific ELISAs.13,14
There are approximately ninety disease-causing pneumococcal
serotypes, and different serotypes are recognised to cause different
patterns of disease. Individual serotypes vary in properties
including their propensity to cause disease in different organs,
their virulence and invasive potential, ability to colonise the
nasopharynx and likelihood of expressing genes responsible for
conferring antibiotic resistance.15 There are also considerable
geographical differences in the relative prevalence of individual
serotypes and how these change over time.16,17 The factors
responsible for determining temporal changes in the relative
prevalence of individual serotypes are incompletely understood.
There are considerable ‘‘secular’’ changes which probably reflect
Darwinian competition for ecological space between pneumococ-
cal serotypes and between pneumococci and other organisms.18 In
addition there are other recognised influences including selection
pressure from antibiotic use, and more recently from the
introduction of conjugate pneumococcal vaccines.19
The first commercially available conjugate pneumococcal vaccine
Prevenarß was introduced into the routine infant vaccine schedule
in the USA between 2000 and 2001. The first commercially available
version of this vaccine contained antigen for serotypes 4, 6B, 9 V, 14,
18C, 19F and 23F which were the seven most common causes of
culture positive pneumococcal disease prevalent in the USA at the
time.20 Introduction of the vaccine was associated with an initial
rapid reduction in the incidence of pneumonia and complicated
disease in both immunised patients and the general population,
presumably as a consequence of increased herd immunity.21
Unfortunately some of these benefits were short lived and there
followed an increase in severe invasive pneumococcal disease related
to serotypes not present in the seven valent vaccine, especially 19A
disease.22,23 19A disease is notable for being particularly associated
with a severe, virulent necrotising pneumonia which is often
associated with resistance to multiple antibiotics.24
242 D.A. Spencer, M.F. Thomas / Paediatric Respiratory Reviews 15 (2014) 240–245
The problem of an increase in pneumococcal disease from non-
vaccine serotypes was not unexpected and has been termed
‘‘replacement disease’’.18,24 The magnitude of this problem appears
to vary between different countries, and the general consensus has
been that for most countries the overall benefit from reduction in
disease related to vaccine serotypes has been much greater than
the increase in disease from non-vaccine serotypes. Moreover, the
hope is that much replacement disease will be from non-vaccines
serotypes which are intrinsically less virulent than disease related
to vaccine serotypes. It is also theoretically possible that
introduction of multivalent conjugate vaccines into routine infant
vaccine schedules may result in an increase in infection from other
organisms; especially those frequently present colonising the
nasopharynx such as Staphylococcus aureus and Group A strepto-
coccus. To date there has been no evidence that this potential
problem has materialised. There has been one report of at least a
transient increase in nasopharyngeal colonisation with staphylo-
cocci following vaccination with Prevenar 7ß in Dutch infants, but
this has not resulted in any adverse clinical consequences.25
Following the introduction of the seven valent conjugate
vaccine, two other vaccines with coverage against an extended
range of pneumococcal serotypes have been licensed and
introduced into routine infant vaccine programmes across the
globe. Prevenar 13ß (referred to in some countries as Prevnar 13ß )
contains antigens to protect against six additional pneumococcal
serotypes namely 3, 5, 6A, 7F and 19A compared to the seven
valent vaccine. The ten valent vaccine Synflorix contains antigen
to protect against three additional serotypes compared to the
seven valent vaccine, namely 1, 5 and 7F. Prevenar 13ß replaced
Prevenar 7ß in the routine infant vaccination schedule in the UK in
2010. Whilst it would be premature to confirm that this
development has definitely resulted in a reduction in necrotising
pneumonia and empyema, the serotype coverage of this vaccine
would certainly be expected to cover a significantly higher
percentage of relevant serotypes than the previous vaccine.
Preliminary findings from the UK-ESPE enhanced pneumococcal
empyema surveillance programme suggest that this is indeed
proving to be the case, and that a worrying increase in 19A disease
appears to have been aborted.
Staphylococcal disease
S. aureus has long been recognised as a cause of necrotising
pneumonia in children, but recently it has been the focus of
considerable interest following the recognition of the contribution
of the staphylococcal virulence factor Panton-Valentine leukocidin
(PVL). In an important study in 2002, Gillet et al reported the
association between PVL expression and severe and often fatal
staphylococcal necrotising pneumonia in previously healthy
children and young adults for the first time.26 Descriptions of
cases of PVL-positive staphylococcal (PVL-SA) necrotising pneu-
monia have since emerged from across the world.27–29 Panton-
Valentin leukocidin is an example of a syngeroghymenothrophic
toxin. In vitro, it causes lysis of leucocytes by causing pore
formation in their cell membranes leading to the release of
cytotoxic granules which in turn drive lung inflammation and
injury.30 Mortality in Gilet et al’s original series was 63% and
similar levels have been observed elsewhere.26–28
Histopathological examination of the lungs of patients who
died from PVL-SA necrotising pneumonia illustrated the severity of
the necrotising process, with macroscopic massive ulceration and
necrosis of the tracheal and bronchial mucosae. The bases of the
ulcers were composed of necrotic tissue devoid of inflammatory
cells and the lung parenchyma contained massive alveolar
haemorrhage with necrosis of the interalveolar septa and large
clusters of gram positive cocci.26
Downloaded from ClinicalKey.com at Universidad Autonoma de Guadalajara September 27, 2016.
For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.
PVL-production is rare in isolates of S. aureus in the UK, with less
than 2% of isolates producing the toxin.31 However, that rate
increases significantly to 15% when isolates associated with
pneumonia are examined separately. Cases of PVL-positive S.
aureus causing disease increased in the UK between 2005 and 2008
but have subsequently declined. It is not yet clear whether the
increases seen were true increases in prevalence or due to
increasing efficacy of surveillance and diagnostic procedures.
The relationship between methicillin resistance (MR) and PVL
production remains controversial. The rate of MR in Gilet et al’s
original series was low at 6%, yet cases in the USA have shown a
much higher prevalence of MR resistance.30 This has been
attributed to the high prevalence of the MR S. aureus USA300
clone which carries the genes for PVL expression.30 To date isolates
of PVL-SA outside of the USA have demonstrated a high level of
clonal variability, without evidence of one S. aureus clone type
predominating.26,31
Non-PVL MR S. aureus (MRSA) infection may also be an
increasing problem. Between 1992 and 2002 S. aureus became the
leading cause of empyema in a large Texas children’s hospital,
overtaking S. pneumoniae.32 Latterly, over 75% of S. aureus isolates
were methicillin resistant. However, while this change does not
appear to have been observed in other settings, clinicians need to
be alert to the possibility of MRSA infection.
CLINICAL FEATURES OF NECROSTING PNEUMONIA
The overall features of necrotising pneumonia are similar to
those of an uncomplicated pneumonia, usually with pleural
involvement. The main distinction is that the patient is clinically
much sicker and has usually failed to respond adequately to
appropriate antibiotics by the time that the diagnosis is consid-
ered. The child may well have persisting fever, tachycardia,
hypoxia and tachypnoea with poor peripheral perfusion. Chest
signs may include bronchial breathing, the stony dullness of a
pleural effusion and possibly signs of mediastinal shift.
Cases of PVL-positive staphylococcal necrotising pneumonia
are characterised by high fever (>39oC), increased risk of
haemoptysis and purulent expectoration when compared to
non-PVL staphylococcal pneumonia. In addition, there is often a
history of recent S. aureus infection either in the affected individual
or close family contacts. There may also be a history of preceding
influenza infection. Laboratory models have suggested that
influenza infection may predispose to staphylococcal pneumonia
by suppression of Th-17, T-helper cells.27 PVL-positive staphylo-
coccal necrotising pneumonia may also cause purpura fulminans.
Predictors of mortality in PVL-positive staphylococcal necrotis-
ing pneumonia in the largest cohort of cases yet analysed, were the
presence of pulmonary haemorrhage, leucopenia and erythro-
derma.28 Later series have reported similar findings and the
presence of these features should act as a trigger for aggressive
management.
INVESTIGATIONS
All patients should have routine blood count and serum
biochemistry along with blood culture if pyrexial. An antistrepto-
lysin titre and acute viral and mycoplasmal serology should also be
sent. Anaemia is common, as are thrombocytosis and thrombocy-
topenia. Frank renal failure is unusual, but hyponatraemia is not
uncommon.
It is unusual for paediatric patients to be able to expectorate
sputum, but if produced this should be sent for bacterial and viral
studies. Nasopharygeal aspirates can reasonably be taken for these
studies in younger infants. Bronchoscopy has not gained general
acceptance as a method for obtaining bronchoalveolar lavage for
 D.A. Spencer, M.F. Thomas / Paediatric Respiratory Reviews 15 (2014) 240–245
Figure 1. Plain radiograph illustrating necrotic pneumonia caused by
pneumococcal 19A infection in a young infant. Note air-fluid level in right sided
abscess and extensive right lung involvement. This child required ECMO support
but eventually made a good recovery.
microbiological and viral studies because of valid concerns
regarding the potential for adverse effects and increasing
respiratory distress, although a Belgian study did find that this
appears to be effective and safe in selected patients.33 There is
increasing reluctance to perform a pleural tap for diagnostic
purposes, although this is generally a very safe procedure. If pleural
fluid is obtained either by tap or at thoracotomy it should be sent
for bacterial culture including mycobacterial studies. More
advanced techniques including bacterial PCR on pleural fluid
and blood as well as serotype-specific ELISAs and the Binax Now
test to diagnose pneumococcal infection are now beginning to
become available as routine clinical tools in many centres. Pleural
fluid should be sent for glucose level, pH, LDH and total protein
level as well as cytological analysis.
RADIOLOGY
All patients will have a routine chest radiograph performed. As
well as demonstrating pneumonic changes, this may indicate the
presence and approximate volume of pleural fluid along with an
indication of any mediastinal shift due to pleural involvement. The
plain chest radiograph will reveal the presence of larger cavities
and abscesses, although significant changes visible only on CT can
easily be missed (Figures 1 and 2). The plain radiograph can also
not tell the nature of any pleural involvement, for which
ultrasonography is required to determine whether fluid is
homogenous or loculated, and whether there is pleural thickening.
Chest CT with contrast is an increasingly useful investigation for
the assessment of suspected necrotising pneumonia. CT findings
include the loss of normal parenchymal architecture2, decreased
parenchymal enhancement, multiple thin walled fluid or air filled
cavities without enhancing borders and the ‘‘mass within a mass’’
or ‘‘air crescent’’ sign of pulmonary gangrene as well as the
presence of loculated pleural fluid with pleural thickening. These
changes can develop very rapidly and the increasing availability of
ultrafast CT machines which use very low radiation doses is a
particularly useful and welcome development which allows repeat
scanning to be performed safely and without requiring without
general anaesthesia.
Downloaded from ClinicalKey.com at Universidad Autonoma de Guadalajara September 27, 2016.
For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.
243
Figure 2. Cross-section from a CT scan taken of the same patient on the same day as
Figure 1. Note relationship between the consolidation in the right lower lobe seen in
the plain radiograph and air-filled necrotic cavity.
MANAGEMENT
General initial management should be similar to that for non-
complicated pneumonia. Patients should be given supplemental
oxygen if they are hypoxic. Adequate analgesia is imperative,
especially as the intensely sharp discomfort of pleuritic pain may
result in shallow breathing and a reluctance of the patient to cough
adequately.
Particular care should be made in the assessment and manage-
ment of circulating blood volume. It has previously been suggested
that patients with pneumonia are prone to the syndrome of
inappropriate antidiuretic hormone secretion (SIADH) resulting in
patients being managed with inappropriate volume restriction. It is
now becoming recognised that the biochemical abnormalities see in
pneumonia are more likely to be due to volume and salt depletion
rather than SIADH, and that as such volume replacement is more
likely to be necessary than restriction.34
Some patients will require ventilatory support, and occasionally
extracorporeal membrane oxygenation (ECMO) may be lifesaving.
Antibiotic therapy should be guided by the regional prevalence
of individual organisms and national guidelines. In most countries
it will be important to cover for S. pneumoniae, S. aureus and Group
A Streptococcal infection, but antibiotic sensitivity patterns to
these organisms vary widely across the world. Doses should be at
the top of the recommended range. There is increasing evidence
that uncomplicated pneumonia in children can usually be
managed with oral antibiotics. This is not the appropriate initial
route for children with life-threatening disease because of
concerns concerning inconsistent absorption and gastrointestinal
adverse effects from high dose antibiotics, so intravenous therapy
is mandatory.
Guidelines for the management of PVL-SA necrotising pneu-
monia have been produced by the UK Health Protection Agency
and are available from: http://www.hpa.org.uk/webc/HPAweb-
File/HPAweb_C/1218699411960. Recommendations include add-
ing Linezolid or Clindamycin (toxin suppressing agents) to
standard empiric treatment. If further deterioration is seen then
additional therapy with intravenous immunoglobulin (IVIG) and
rifampicin is suggested. Aggressive supportive therapy is also
strongly recommended and intensive care admission is frequently
needed for these patients. Several case reports in the literature
244 D.A. Spencer, M.F. Thomas / Paediatric Respiratory Reviews 15 (2014) 240–245
describe the use of ECMO in children with severe PVL-SA
necrotising pneumonia.27 The outcomes described for infants
and those with fulminant disease appear poor but the available
data is limited at present and this option should be considered in
cases refractory to standard treatment.
There is widespread variation in the approach to the approach
to clearing of infected material from the pleural cavity. Chest
drainage alone is not recommended as it is associated with
prolonged hospitalisation and morbidity.12 Intrapleural installa-
tion of Urokinase has found favour in many centres, but is
sometimes associated with incomplete clearance of infection from
the pleural cavity, and there is a subsequent requirement for
thoracotomy in about 10% of cases.35 Early surgical intervention
with either mini-thoracotomy or Video-Assisted Thoracoscopic
Surgery (VATS) is associated with early discharge from hospital,
but requires the availability of skilled paediatric thoracic
surgeons.36,37 In addition to the clearance of the pleural infection,
large abscesses may require to be de-roofed with over-sewing of
the abscess cavity.
Bronchopleural fistula is a recognised complication in this
group of patients, and is not necessarily related to surgical
intervention. This may require prolonged drainage, and sometimes
surgery is required to seal the fistula with fibrin glue or other
substances.
PROGNOSIS
Necrotising pneumonia is associated with significant morbidity
and mortality, but in a previously well child death is now
remarkably uncommon in children managed in specialised units
with access to modern intensive care and paediatric thoracic
surgical facilities. Recovery can be prolonged with persisting
respiratory symptoms, reduced lung function and limited energy
levels for many months after the acute illness, but the great
majority of patients do recover fully. Cavities previously visible on
plain chest radiographs do usually resolve, and whilst CT scans are
not frequently repeated in children without good clinical reason
there is some anecdotal evidence that dramatic improvement
towards normality can also be seen with this sensitive modality. A
small number of patients are left with some residual functional
impairment with evidence of small airways disease, bronchiectasis
and persistent reduction in lung function.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ROLE OF FUNDER
Commissioned review without external funding.
PRACTICE POINTS
 Necrotising pneumonia in children appears to be increasing.
 Pneumococcal infection remains the predominant cause
but PVL-positive staphylococcal infection is associated
with a severe necrotic pneumonia.
 High quality supportive care is crucial and particular
attention should be paid to analgesia and fluid balance in
these patients.
 Conservative management of lung necrosis remains
preferential but aggressive management of pleural in-
volvement is often required.
Downloaded from ClinicalKey.com at Universidad Autonoma de Guadalajara September 27, 2016.
For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.
References
1. Lannec RTH. Traite de l’auscultation mediate et des maladies des poumons et du
coeur, 2nd ed., Paris: JS Chaude; 1826.
2. Sawicki GS, Lu FL, Valim C, Cleveland RH, Colin AA. Necrotising pneumonia is an
increasingly detected complication of pneumonia in children. Eur Respir J
2008;3:1285–91.
3. Hsieh Y-C, Hsiao C-H, Tsao P-N, et al. Necrotizing pneumococcal pneumonia
in children: the role of pulmonary gangrene. Pediatr Pulmonol 2006;41:
623–9.
4. Hsieh Y-C, Hsueh P-R, Lu C-Y, Lee P-I, Lee C-Y, Huang L-M. Clinical manifesta-
tions and molecular epidemiology of necrotizing pneumonia and empyema
caused by Streptococcus pneumoniae in children in Taiwan. Clin Infect Dis
2004;38:830–5.
5. Rees JH, Spencer DA, Parikh D, Weller P. Increase in incidence of childhood
empyema in West Midlands, UK. Lancet 1997;349:402.
6. Roxburgh CS, Youngson GG, Townend JA, Turner SW. Trends in pneumonia
and empyema in Scottish children in the past 25 years. Arch Dis Child
2008;93:316–8.
7. François P, Desrumaux A, Cans C, Pin I, Pavese P, Labarère J. Prevalence and risk
factors of suppurative complications in children with pneumonia. Acta Pædiatr
2010;99:861–6.
8. Byington CL, Spencer LY, Johnson TA, et al. An epidemiological investigation of a
sustained high rate of pediatric parapneumonic empyema: Risk factors and
microbiological associations. Clin Infect Dis 2002;34:434–40.
9. Grijalva CG, Nuorti JP, Zhu Y, Griffin MR. Increasing incidence of empyema
complicating childhood community acquired pneumonia in the United States.
Clin Infect Dis; 50: 805–13.
10. Finley C, Clifton J, Fitzgerald JM, Yee J. Empyema: an increasing concern in
Canada. Can Respir J 2008;15:85–9.
11. Strachan R, Jaffé A. Assessment of the burden of paediatric empyema in
Australia. J Paediatr Child Health 2009;45:431–6.
12. Balfour-Lynn IM, Abrahamson E, Cohen G, et al. BTS guidelines for the
management of pleural infection in children. Thorax 2005;60(Suppl. 1):
i1–21.
13. Saglani S, Harris KA, Wallis C, Hartley JC. Empyema: the use of broad range 16S
rDNA PCR for pathogen detection. Arch Dis Child 2005;90:70–3.
14. Eltringham G, Kearns A, Freeman R, et al. Culture-negative childhood empyema
is usually due to penicillin-sensitive Streptococcus pneumoniae capsular sero-
type 1. J Clin Microbiol 2003;41:521–2.
15. Obaro S, Adegbola R. The pneumococcus: carriage, disease and conjugate
vaccines. J Med Microbiol 2002;51:98–104.
16. Hausdorff WP, Feikin DR, Klugman KP. Epidemiological differences among
pneumococcal serotypes. Lancet Infect Dis 2005;5:83–93.
17. Hausdorff WP. Invasive pneumococcal disease in children: geographic and
temporal variations in incidence and serotype distribution. Eur J Pediatr
2002;161(Suppl. 2):S135–9.
18. Lipsitch M. Bacterial Vaccines and Serotype Replacement: Lessons from Hae-
mophilus influenzae and Prospects for Streptococcus pneumoniae. Emerg Infect
Dis 1999;5:336–45.
19. Andrade AL, Toscano CM, Minamisava R, Costa PS, Andrade JG. Pneumococcal
disease manifestation in children before and after vaccination: What’s new?
Vaccine 2011;29(Suppl. 3):C2–14.
20. Dinleyici EC, Yargic ZA. Pneumococcal conjugated vaccines: impact of PCV-7
and new achievements in the postvaccine era. Expert Rev Vaccines 2008;
7:1367–94.
21. Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR.
Decline in pneumonia admissions after routine childhood immunisation with
pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet
2007;369:1179–86.
22. Miller E, Andrews NJ, Waight PA, Slack MPE, George RC. Herd immunity and
serotype replacement 4 years after seven-valent pneumococcal conjugate
vaccination in England and Wales: an observational cohort study. Lancet Infect
Dis 2011;11:760–8.
23. Pelton SI, Huot H, Finkelstein JA, et al. Emergence of 19A as virulent and
multidrug resistant pneumococcus in Massachusetts following universal im-
munization of infants with pneumococcal conjugate vaccine. Pediatr Infect Dis J
2007;26:468–72.
24. Pelton SI. Replacement pneumococcal disease in perspective. Clin Infect Dis
2008;46:1353–5.
25. van Gils EJM, Hak E, Veenhoven RH, et al. Effect of seven-valent pneumococcal
conjugate vaccine on Staphylococcus aureus colonisation in a randomised
controlled trial. PLoS ONE 2011;6:e20229.
26. Gillet Y, Issartel B, Vanhems P, Fournet J-C, Lina G, Bes M, et al. Association
between Staphylococcus aureus strains carrying gene for Panton-Valentine
leukocidin and highly lethal necrotising pneumonia in young immunocompe-
tent patients. Lancet 2002;359:753–9.
27. Schwartz K, Nourse C. Panton–Valentine leukocidin-associated Staphylococcus
aureus necrotizing pneumonia in infants: a report of four cases and review of
the literature. Eur J Pediatr 2012;171:711–7.
28. Gillet Y, Vanhems P, Lina G, et al. Factors predicting mortality in necrotizing
community-acquired pneumonia caused by Staphylococcus aureus containing
Panton-Valentine Leukocidin. Clin Infect Dis 2007;45:315–21.
29. Thomas B, Pugalenthi A, Chilvers M. Pleuropulmonary complications of PVL-
positive Staphylococcus aureus infection in children. Acta Paediatr 2009;98:
1372–5.
 D.A. Spencer, M.F. Thomas / Paediatric Respiratory Reviews 15 (2014) 240–245 245

30. Gillet Y, Etienne J, Lina G, Vandenesch F. Association of necrotizing pneumonia
with Panton-Valentine Leukocidin–producing Staphylococcus aureus, regardless
of Methicillin resistance. Clin Infect Dis 2008;47:985–6.
31. Holmes A, Ganner M, McGuane S, Pitt TL, Cookson BD, Kearns AM. Staphylococ-
cus aureus isolates carrying Panton-Valentine Leucocidin genes in England and
Wales: Frequency, characterization, and association with clinical disease. J Clin
Microbiol 2005;43:2384–90.
32. Schultz KD, Fan LL, Pinsky J, et al. The changing face of pleural empyemas in
children: epidemiology and management. Pediatrics 2004;113:1735–40.
33. De Schutter I, Malfroot A, Piérard D, Lauwers S. Pneumococcal serogroups and
serotypes in severe pneumococcal pneumonia in Belgian children: theoretical
coverage of the 7-valent and 9-valent pneumococcal conjugate vaccines.
Pediatr Pulmonol 2006;41:765–70.
34. Harris M, Clark J, Coote N, et al. British Thoracic Society guidelines for the
management of community acquired pneumonia in children: update 2011.
Thorax 2011;66(Suppl. 2):ii1–23.
35. Thomson AH, Hull J, Kumar MR, Wallis C, Balfour Lynn IM. Randomised trial of
intrapleural urokinase in the treatment of childhood empyema. Thorax
2002;57:343–7.
36. Li S-TT, Gates RL. Primary Operative Management for Pediatric Empyema:
Decreases in Hospital Length of Stay and Charges in a National Sample. Arch
Pediatr Adolesc Med 2008;162:44–8.
37. Avansino JR, Goldman B, Sawin RS, Flum DR. Primary Operative Versus Non-
operative Therapy for Pediatric Empyema: A Meta-analysis. Pediatrics 2005;
115:1652–9.

CME SECTION c) Pneumococcal serotype 19A is frequently antibiotic resistant

This article has been accredited for CME learning by the d) Limited valency pneumococcal vaccines have been associat-
European Board for Accreditation in Pneumology (EBAP). You ed with ‘replacement disease’
can receive 1 CME credit by successfully answering these 3. Clinical features of PVL-positive staphylococcal necrotising
questions online. pneumonia in children include:
a) Erythroderma
(A) Visit the journal CME site at http://www.prrjournal.com. b) Family history of recent staphylococcal infection
(B) Complete the answers online, and receive your final score c) Haemoptysis
upon completion of the test. d) Preceding influenza infection
(C) Should you successfully complete the test, you may e) High fever (>398C)
download your accreditation certificate (subject to an 4. Sensible routine investigations in necrotic pneumonia
administrative charge). include:
a) Sputum culture
b) Pleural tap
CME QUESTIONS
c) Bronchoscopy
d) CT scanning
1. Causes of necrotic pneumonia in children include:
5. The following statements are true or false:
a) Streptococcus pneumoniae
a) Necrotising pneumonia in children is associated with a high
b) Respiratory syncytial virus
mortality rate
c) Adenovirus
b) Intra-venous immunoglobulin is not recommended for severe
d) Mycoplasma pneumoniae
PVL-positive staphylococcal necrotising pneumonia
e) Staphylococcus aureus
c) Broncho-pleural fistula formation is not a recognised
2. Regarding pneumococcal infection in children, the following
complication of necrotising pneumonia
statements are true:
d) Initial oral antibiotic treatment is recommended in children
a) Less than ten pneumococcal serotypes are recognised
with necrotising pneumonia
b) There are no differences in virulence, clinical disease profile
and outcomes between pneumococcal serotypes

Downloaded from ClinicalKey.com at Universidad Autonoma de Guadalajara September 27, 2016.

For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.