Review
Complicated pneumonia in children
Lancet 2020; 396: 786–98
Salesi Children’s Hospital
Foundation, Ancona, Italy
(F M de Benedictis MD);
Department of Pediatrics,
Hadassah Hebrew University
Hospital, Jerusalem, Israel
(E Kerem MD); Child Health
Division, Menzies School of
Health Research, Darwin, NT,
Australia (A B Chang PhD);
Department of Respiratory and
Sleep Medicine, Queensland
Children’s Hospital,
South Brisbane, QLD, Australia
(A B Chang); Centre for
Healthcare Transformation,
Queensland University of
Technology, Brisbane, QLD,
Australia (A B Chang); Division
of Pediatric Pulmonology,
Miller School of Medicine,
University of Miami, Miami, FL,
USA (A A Colin MD);
Department of Paediatrics and
Child Health, Red Cross
Children’s Hospital, Cape Town,
South Africa (H J Zar PhD);
MRC Unit on Child and
Adolescent Health, University
of Cape Town, Cape Town,
South Africa (H J Zar);
Department of Paediatric
Respiratory Medicine, Royal
Brompton Hospital, London,
UK (A Bush MD); and National
Heart and Lung Institute,
Imperial School of Medicine,
Imperial College London,
London, UK (A Bush)
Correspondence to:
Dr Andrew Bush, Department of
Paediatric Respiratory Medicine,
Royal Brompton Hospital,
London SW3 6NP, UK
a.bush@imperial.ac.uk
For more on the British Thoracic
Society see https://www.brit-
thoracic.org.uk/
786 www.thelancet.com Vol 396 September 12, 2020
Fernando M de Benedictis, Eitan Kerem, Anne B Chang, Andrew A Colin, Heather J Zar, Andrew Bush
Complicated community-acquired pneumonia in a previously well child is a severe illness characterised by
combinations of local complications (eg, parapneumonic effusion, empyema, necrotising pneumonia, and lung
abscess) and systemic complications (eg, bacteraemia, metastatic infection, multiorgan failure, acute respiratory
distress syndrome, disseminated intravascular coagulation, and, rarely, death). Complicated community-acquired
pneumonia should be suspected in any child with pneumonia not responding to appropriate antibiotic treatment
within 48–72 h. Common causative organisms are Streptococcus pneumoniae and Staphylococcus aureus. Patients have
initial imaging with chest radiography and ultrasound, which can also be used to assess the lung parenchyma, to
identify pleural fluid; CT scanning is not usually indicated. Complicated pneumonia is treated with a prolonged
course of intravenous antibiotics, and then oral antibiotics. The initial choice of antibiotic is guided by local
microbiological knowledge and by subsequent positive cultures and molecular testing, including on pleural fluid if a
drainage procedure is done. Information from pleural space imaging and drainage should guide the decision on
whether to administer intrapleural fibrinolytics. Most patients are treated by drainage and more extensive surgery is
rarely needed; in any event, in low-income and middle-income countries, resources for extensive surgeries are scarce.
The clinical course of complicated community-acquired pneumonia can be prolonged, especially when patients have
necrotising pneumonia, but complete recovery is the usual outcome.
Introduction extrapolated to low-income and middle-income areas with
Community-acquired pneumonia (CAP) remains the caution.
largest single cause of morbidity and mortality worldwide
in children aged between 28 days (ie, outside the neonatal Epidemiology
period) and 5 years.1 Although most children with CAP The British Thoracic Society Paediatric Pneumonia Audit
recover, some children develop local (pulmonary) or reported that 3% of cases of CAP become complicated.3
systemic complications. Complicated community-acquired A retrospective analysis of medical records showed that
pneu­monia (CCAP) consists of one or more of parapneu­ children younger than 5 years comprised 143 (57%) of
monic effusion, empyema, necrotising pneumonia, and the 251 children admitted to eight paediatric hospitals in
lung abscess, the local complications of CAP.2 CCAP is Canada for CCAP and 73 (51%) of the 144 admitted to
characterised by severe illness, prolonged hospitalisation, three major hospitals in Jerusalem, Israel, for CCAP.4,5 A
and a protracted disease course; however, most patients few children (about 10%) admitted to hospital with CAP
fully recover. Systemic complications include sepsis and are also found to have a simple parapneumonic effusion,
septic shock, metastatic infection, multiorgan failure, and a considerable proportion will develop severe compli­
acute respiratory distress syndrome, disseminated intra­ cations.6 Necrotising pneu­monia was first described in
vascular coagulation, and death. This Review focuses on children in 1994,7 and has since been increasingly
CCAP in otherwise previously healthy children. Although reported, an increase only partly explained by a greater
we have sourced literature from as many health-care awareness and the use of more sensitive imaging
settings as we can, we acknowledge that most data are techniques for diagnosis. Necrotising pneumonia com­
from high-income countries, and should only be plicates up to 7% of all cases of paediatric CAP.8 The
introduction of the 7-valent pneumococcal conjugate
vaccine (PCV7), which covers serotypes 4, 6B, 9V, 14, 18C,
Search strategy and selection criteria 19F, and 23F, into immunisation programmes initially
We searched MEDLINE, Current Contents, PubMed, and the led to a declining incidence of CAP in childhood;9,10
Cochrane Library for articles published in English between however, the PCV7 was associated with an increased
Jan 1, 1990, and Dec 31, 2019, using the keywords: incidence of empyema, mainly due to non-vaccine
“complicated pneumonia”, or “pleural effusion”, or serotypes.11–14 Following the global replacement of the
“empyema”, “necrotizing pneumonia”, “lung abscess”, PCV7 with the 13-valent PCV (PCV13), which covers the
“bronchopleural fistula”, “pneumatocele”, and “children”. additional serotypes 1, 3, 5, 6A, 7F, and 19A, the incidence
We included reviews, randomised controlled trials, and other and the rate of hospitalisation for empyema decreased
types of clinical research that focused on children 18 years and substantially.15–19
younger. We largely selected publications published between Three European studies found that vaccination with
2009 and the end of 2019. We cite review articles and book the PCV13 reduced the incidence of parapneumonic
chapters in this Review to provide readers with additional effusion and empyema in children, without causing
details and more references than this Review can include. serotype shifting.20–22 Serotypes 1, 3, and 19A, all of which
We also consulted our personal archives of references. are covered by the PCV13, accounted for most of the
Streptococcus pneumoniae strains detected in studies from

Europe.20–23 Nevertheless, the reduction in the incidence
of empyema following the introduction of the PCV13
has not been universal.24,25 For example, a Canadian
retrospective, population-based cohort study24 of invasive
pneu­mococcal disease spanned the introduction of the
PCV. The time periods examined were 2000–04 (before
and early in the introduction of the PCV), 2005–09
(when the PCV7 was in common use), and 2010–14 (the
introduction of the PCV13). Over time, the incidence of
pneumococcal disease decreased, but empyema, admis­
sion to intensive care, and mortality increased. However,
as discussed in the paper by Haggie and colleagues,25 the
data might have been biased by the use of the PCV13,
which might have limited protection efficacy against
serotype 3.20 The incidence of bacteraemic CAP associated
with empyema immediately increased in Spain when the
PCV13 was withdrawn because of funding issues.26
Cause
Accurate data on the cause of CAP are hampered by
hetero­geneity in case definitions and difficulty in obtaining
lower airway samples and interpreting microbiology
results.27 Studies in the UK,28 the USA (EPIC),29 South
Africa,30 and low-income and middle-income countries31
(eg, Cambodia, China, Haiti, India, Madagascar, Mali,
Mongolia, and Paraguay) have shown the importance of
viruses in children hospitalised with CAP, especially in
settings of high immunisation coverage with the PCV.
These data are supported by a systematic review32 and the
PERCH study.33 The PERCH study found that the
respiratory syncytial virus was the most common cause of
pneumonia in children aged 1–59 months admitted to
hospitals in Asia and Africa with severe or very severe
pneumonia. Alone, viruses rarely cause complicated pneu­
monia, but viral and bacterial co-infection are common in
the context of CAP.
Large studies from the USA,34 Australia,35 and Israel5
done before the PCV13 was introduced found that
S pneumoniae was the main pathogen in children with
parapneumonic effusion, empyema, or both. These data
have been supported by studies in Europe done after the
introduction of PCV13.20,22 However, immunisation with
the PCV13 is associated with a reduction in invasive
pneumococcal disease36 and a relative increased incidence
of other organisms, particularly Streptococcus pyogenes,22,37
and Staphylococcus aureus22,30 in children with CCAP.
Haemophilus influenzae, Mycoplasma pneumoniae, and
Pseudomonas aeruginosa are less common causes of
CCAP. In areas with a high prevalence of tuberculosis,
Mycobacterium tuberculosis has increasingly been asso­
ciated with presentation with acute pneumonia30,33 and
pleural effusion.38 S pneumoniae is also the most common
cause of necrotising pneumonia in children. Of the
197 bacterial and fungal pathogens detected in single case
reports and case series of necrotising pneumonia, mostly
done before the introduction of the PCV13, 116 (59%)
were S pneumoniae and 45 (23%) were S aureus, including
www.thelancet.com Vol 396 September 12, 2020 787
Review
15 meticillin-resistant strains; other less frequently
reported bacteria included S pyogenes, Streptococcus
viridans, P aeruginosa, and anaerobes.8 M pneumoniae has
been detected in children aged 3–14 years with CCAP in
Taiwan39 and China.40 Sporadic cases of necrotising
pneumonia induced by Fusobacterium spp have been
reported in previously healthy children from North
America.41,42 S aureus, S pneumoniae, S pyogenes, Klebsiella
pneumoniae, and anaerobic bacteria (eg, Peptostreptococcus
spp and Fusobacterium spp) are reported to be the most
common pathogens in children with lung abscesses.43
Preceding viral illness (especially influenza) might be an
important risk factor for necrotising pneumonia in
childhood.44 Severe or very severe pneumonia has been
associated with bacterial and viral co-infection in some
reports.29,30,33,45
Pathophysiology
Pleural effusion is the most common manifestation of
CCAP and can be divided into three stages: exudative
(simple parapneumonic effusion), fibrinopurulent (com­
plicated parapneumonic effusion), and the organising
phase with fibroblastic activity and peel formation.
Empyema is used generically to describe an advanced
stage of parapneumonic effusion and, more loosely, to
describe one that predicts a complicated outcome. Pleural
fluid accumulation associated with infection is mainly
due to dysregulation of the balance of hydrostatic and
oncotic pressure between the systemic and pulmonary
circulations and the pleural space.46 In addition, obstruc­
tion of lymphatic drainage by thick pleural fluid and
debris contributes to the accumulation of the effusion.47
Necrotising pneumonia is characterised by extensive
destruction and liquefaction of lung tissue, which can
develop despite the administration of appropriate anti­
biotics. The pathophysiology of necrotising pneumonia is
unclear. Hsieh and colleagues48 have shown vascular
thrombosis in pathological material from a child who died
of necrotising pneumonia, and ultrasound doppler studies
have shown an absence of blood flow in the necrotic areas
of the lungs of children with complicated pneumonia and
parapneumonic effu­sion,49 suggesting extensive vascular
occlusion. A genetic predisposition for the development
of necrotising pneu­ monia has also been suggested.5
Consolidation with necrosis is the hallmark of the initial
stage of necrotising pneumonia.50 Necrosis rapidly
progresses to cavitation (pneumatoceles), which is
generally peripheral and limited to a single lobe.51 Small
cavities can coalesce and form large cysts with air-fluid
levels, mimicking a lung abscess.52 Rupture into the pleural
space can create bronchopleural fistula. Determining
whether air-containing lesions are pneumatoceles or a
loculated pneumothorax can be challenging.
Severe forms of necrotising pneumonia have also
been associated with S aureus strains expressing Panton-
Valentine leukocidin,53–55 a pore-forming exotoxin that
lyses immune cells, potentially releasing tissue-damaging
 Review
proteases.56 S aureus strains positive for Panton-Valentine
leukocidin, which frequently are meticillin-resistant,57
have shown increased affinity for damaged airway
epithelium over strains negative for Panton-Valentine
leukocidin.58 This finding reinforces the notion that
epithelial damage caused by viral infection might be an
important predisposing factor for necrotising pneu­
monia.59 Another S aureus toxin that forms pores,
alpha-hemolysin, which might activate the NLRP3 inflam­
masome, can also lead to necrotising pneumonia.60 A
much rarer complication of CCAP is haemolytic uraemic
syndrome, which is usually caused by S pneumoniae
serotype 3.61,62
A lung abscess is usually a single, thickly walled cavity
containing purulent material that results from sup­
puration and necrosis of parenchyma.63 Developing a
lung abscess secondary to CAP is rare, but can occur
in patients with a pre-existing congenital cystic lung
malformation or be secondary to immune deficiency. The
time course for progression from initial involvement to
abscess formation is usually slow.64 Internal jugular vein
thrombosis (Lemierre’s syndrome) is a rare cause of
metastatic lung abscess.
Risk factors
Chronic conditions, such as immunodeficiencies, mal­
nutrition, chronic lung diseases, and cystic congenital
thoracic malformations, and subacute disorders, such as
inhaled foreign bodies, should be considered as risk
factors for CCAP. Although CCAP predominantly occurs
in otherwise healthy children treated in accor­ dance
with current CAP guidelines,65 it is important to suspect
complications in all children with CAP who are not
responding to therapy. Factors that have been associated
with CCAP in previously healthy children include age
younger than 2 years, long prehospital duration of fever,
asymmetric chest pain at presentation, high acute phase
reactants, low white blood cell count, iron deficiency
anaemia, and pretreatment with ibuprofen or acetamino­
phen. However, interpretation of these associations is
difficult because of the problems of confounding by
indication and reverse causation.66–70
Clinical course
Empyema can mimic uncomplicated pneumonia and
should be suspected in any child who remains pyrexial
or unwell 48–72 h after starting appropriate antibiotic
therapy.71 Dullness to percussion and decreased breath
sounds on physical examination are features of both
pneumonia and pleural effusion; fremitus is reduced in
pleural effusion but is increased in consolidation. The
detection of fremitus depends on the child’s age, size, and
cooperation, and might not be as useful in children as the
detection is in adults. Bronchial breathing can be heard in
lung consolidation, but not in pleural effusion. Pericardial
effusion can coexist with left-sided parapneu­ monic
effusion, and mostly improves with treatment of the
788 www.thelancet.com Vol 396 September 12, 2020
underlying infection and resolution of the pleural
effusion.72 It is important to be aware of metastatic,
bloodborne infections, such as meningitis or septic
arthritis, in children with bacteraemic pneumococcal
pneumonia.
Children with necrotising pneumonia usually look ill,
and have a high fever, cough, and tachypnoea that last
for several days. Hypoxia is common, mild anaemia
and hypoalbuminaemia are characteristic,41 and pleural
effusion is often detectable at physical examination.41,73
Children typically continue to be unwell for several days,
probably because of the release of inflammatory medi­
ators from tissue necrosis.5 Occa­sionally, children with
necrotising pneumonia deteriorate with progressive
respiratory distress, septic shock, multiorgan involvement,
and acute respiratory distress syndrome. The presence of
influenza-like symptoms, haemoptysis, an erythematous
rash, and declining peripheral white blood cell counts
are all signs of possible deterioration, which are often
associated with S aureus strains that produce Panton-
Valentine leukocidin.74,75 Circulatory and ventilation
support in intensive care units,76 or even extracorporeal
membrane oxygenation, might be required in severe
cases.77 Bronchopleural fistula is a uniquely severe
complication of necrotising pneu­ monia with varying
incidence. In a study41 from Boston, MA, USA, ten (13%)
of 80 patients with necrotising pneumonia developed a
bronchopleural fistula; in a study78 from Brazil, 16 (67%) of
24 patients with necro­ tising pneumonia developed a
bronchopleural fistula. A bronchopleural fistula causes
considerable morbidity and protracted hospitalisation,41,79,80
and should be suspected if patients have a persistent
(>24 h) air leak.
Children with lung abscesses usually present with
prolonged low-grade fever and cough; chest pain,
dyspnoea, sputum production, and haemoptysis are less
common. Chest examination might be normal or reveal
signs of consolidation. Complications include pneu­
mothorax, bronchopleural fistula, lung compression,
and mediastinal shift with progressive respiratory
compromise.81
Diagnostic imaging
Chest radiography
A chest radiograph from a patient with CCAP might
show signs of parapneumonic effusion (figure 1),
including blunting of the costophrenic angle and a rim
of fluid ascending the lateral chest wall (meniscus sign).
Large effusions can appear as a complete white out,
making identifying the extent of parenchymal involve­
ment impossible.82 In the initial phase of necrotising
pneumonia, fluid-filled cavitary lesions have the same
density as adjacent consolidated lung and are unlikely
to be identified on a chest radio­graph. In two comparative
imaging studies, cavities were shown on chest radio­
graphy only in 33 (59%) of 56 children and five (22%) of
23 children with necrotising pneumonia defined by
 Review

chest CT.50,83 Conventionally, the diagnosis of lung

abscess is based on chest radiography, which will show a
well demarcated, thick-walled cavity often con­taining an
air-fluid level (figure 2).84 However, chest radiography
might miss the diagnosis in some cases and might not
distinguish an abscess from an underlying congenital
thoracic abnormality or consolidation alone.

Ultrasonography
Ultrasonography is the primary imaging modality used to
evaluate the pleural space (figure 3). This modality is more
sensitive than is chest radiography for detecting small
pleural effusions, can estimate the size of the effusion,
show any fibrinous septations, and can differentiate
pleural effusions from consolidated lung85 and peripheral
lung abscess from empyema.86,87 Ultrasonography is also
useful for guiding the insertion of pleural catheters.88 Early
lung features (air and liquid, deep, and fixed, or not very
dynamic bronchograms) seen on ultra­sonography might
predict the development of complications in children
with CAP,89 and ultrasonography has been proposed as a
point-of-care technique.90 Doppler ultrasound can detect
necrotic changes early (before apparent or more standard Figure 1: Chest radiograph of large right-sided pleural effusion complicating
community-acquired pneumonia
techniques such as CT) and can be used to assess response
to treatment.91
A B
CT
In most children with CCAP, chest CT does not provide
any additional clinically useful information compared
with that gained from ultrasonography,49 and does not
predict outcomes,92 nor alter management.93 Chest CT
should be reserved for when there is diagnostic doubt (eg,
suspicion of malignancy), a complex clinical situation in
which a chest CT could potentially guide intervention
(figure 4; appendix pp 1–2), or when clinical improvement See Online for appendix
does not follow appropriate treatment.94 One guideline
Figure 2: Chest radiographs of lung abscess and necrotising pneumonia
for the management of CCAP found that the use of (A) Lung abscess. A single, thick walled, irregular cavity containing an air-fluid
lung ultrasonography instead of chest CT reduced costs level can be seen (arrow). (B) Necrotising pneumonia. A completely opacified
without changing outcomes.95 Surgeons usually require left hemithorax with multiple necrotic areas can be seen (arrow).
that patients have chest CT scans for operative planning.
If chest CT is deemed necessary, intravenous contrast of C-reactive protein might be useful in indicating an
should be given to better define the pleura. Differentiating underlying bacterial cause for CCAP,97 this measure is
necrotising pneumonia from a lung abscess is typically not completely sensitive or specific in guiding treatment.
done on the basis of observing a rapid transition from a The data on serum procalcitonin in distinguishing
thin walled, fluid-filled com­ partment to cavitation in between bacterial pneumonia and viral pneumonia are
necrotising pneumonia versus observing a thick walled conflicting, but, overall, procalcitonin is unlikely to be
compartment with the presence of fluid with or without useful in making this differentiation.98
air in abscess (figures 2, 4).96 This distinction is important Pneumonia with or without complications is uncom­
because the underlying causes and treatment can differ. monly associated with bacteraemia.12,33,99 Only 65 (2·5%)
of 2568 patients hospitalised with CAP in six children’s
Laboratory testing hospitals in the USA who had a blood culture done had a
Acute phase reactants, such as white blood cell count, positive blood culture.100 Previous empirical antibiotic
C-reactive protein, and erythrocyte sedimentation rate, treatment might have been responsible for this result.101
are often unreliable in distinguishing bacterial from viral ­In a retrospective study5 from Jerusalem (144 children
pneumonia in individuals, but serial measurements can with CCAP), previous antibiotic use reduced the propor­
be helpful in monitoring response to treatment. The tion of positive cultures from 63% to 22%. In another
clinical context is crucial. Although a raised concentration retrospective study102 from North America (369 children

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 Review
A B
Figure 3: Ultrasound findings in different stages of pleural effusion
(A) Simple pleural effusion with uniform echodensity (arrow). (B) Complex loculated effusion with debris (arrow).
Courtesy of Tom Semple, Royal Brompton Hospital, London, UK.
A B
Figure 4: Chest CT in complicated community-acquired pneumonia
(A) Lung abscess. A large cavity containing an air-fluid level can be seen. (B) Necrotising pneumonia with cavitation.
with empyema), previous antibiotic use reduced the
proportion of positive cultures from 67% to 30%.
Obtained pleural fluid should undergo cytological
(cell count and cell differential), biochemical, and
microbiological analysis, including Gram staining, acid-
fast bacilli staining, culture with antibiotic sensitivity
testing of any bacterial pathogens present, PCR for
common pathogens, and testing for M tuberculosis by use
of Xpert Ultra and liquid mycobacterial culture. Bacterial
yield is invariably higher in pleural fluid cultures than in
blood cultures in empyema.5,20,22
Molecular diagnostic tests, which are based on the
amplification of DNA and the detection of specific genes,
have been a major advance in the diagnosis of respiratory
infections.103 PCR tests on samples of blood and pleural
fluid are more sensitive than is culture in identifying
pathogens, especially in the context of preceding antibiotic
treatment.17,20,22,104–106 Doing PCR on blood samples is usually
less specific and less sensitive than doing PCR on
pleural fluid.107 PCR also offers the advantage of pro­viding
results and serotyping within a few hours.108
The inability to distinguish colonising organisms
from pathogenic organisms is a key limitation for the use
of some specimens, such as induced sputum, naso­
pharyngeal samples, and oropharyngeal samples.109,110
However, these specimens might be useful in the detec­
tion of organisms that are almost invariably pathogenic
790 www.thelancet.com Vol 396 September 12, 2020
(eg, respiratory syncytial virus and influenza virus).30
The specificity and sensitivity of all these methods are
unknown. Most experience with induced sputum in
childhood pneumonia is in the context of tuberculosis, a
context in which this technique has been shown to be an
effective diagnostic test, especially if two specimens are
taken.111 The sputum induction test is not a useful
diagnostic test in childhood CAP.112
Flexible bronchoscopy with bronchoalveolar lavage is
recommended by the Paediatric Infectious Diseases
Society and the Infectious Disease Society of America for
patients with CCAP without a microbiological diagnosis
on initial testing, or for those who are not responding to
treatment.113 However, pathogenic yield is very small in a
child with intact immunity,114 and this technique is not
available in many centres, especially in low-income and
middle-income countries.
The rapid urine antigen assay is a sensitive but non-
specific method for detecting invasive pneumococcal
disease.115 This assay is not useful for diagnosing pneu­
monia in children because this method cannot distinguish
between pneumococcal colonisation and pneumococcal
disease.116 However, unlike with urine, detection of the
pneumococcal antigen in pleural fluid from children has a
high positive predictive value for pneumococcal empy­
ema.117 By use of a commercially available kit based around
an immunochromatographic test, the sensitivity of this
method is reportedly high in children with pneumococcal
empyema (77% in one study and 88% in another), as is the
specificity (71% and 94%).118,119 Tests for M tuberculosis
should be done if the patient has a lymphocytic effusion or
risk factors for tuberculosis, or lives in an area with a high
incidence of tuberculosis.116
Percutaneous, image-guided aspiration and drainage
of a lung abscess are sometimes used diagnostically.
An organism can usually be identified on the culture
of aspirated material despite antecedent antibiotic
therapy.120 However, culturing lung aspirates is not a
routine clinical test. Leakage from an abscess to the
pleural space can occur during and after drainage, but
the risk of bronchopleural fistulae appears to be less
when aspirating lung abscesses than when aspirating
necrotising pneumonias.121
Management
There is no general consensus on the optimal manage­
ment of many aspects of CCAP. Recommendations are
largely based on expert opinion and not on high-quality,
randomised controlled trials. Children should be referred
to a centre with expertise in the management of CCAP.
We report on the role of specific interventions in CCAP in
the appendix (pp 3–5).
Antibiotics
Antimicrobials are essential in the treatment of CCAP,
either alone or in combination with interventional
procedures. The evolution of parapneumonic effusion is

largely dependent on the time between the onset of
disease and the start of therapy; indeed, the early
initiation of appropriate antibiotics might, in some
cases, prevent the development of effusion and restrict
the progression to empyema.122 Antibiotic treatment
alone is usually suf­ficient in children with small
parapneumonic effusions, no mediastinal shift, and no
respiratory compromise.123,124 Antibiotics are also effective
at treating children with necrotising pneumonia, even
when severe cavitation is present.5,52 A prolonged course
of antibiotics is effective in most children with lung
abscesses.120
The choice of antibiotic should be based on international
and local guidelines,113,125 and take into consideration local
patterns of antibiotic resistance and whether the child has
any underlying comorbidities. Initial therapy must be
effective against S pneumoniae (the commonest cause of
CCAP) and S aureus, guided by local bacteriological
knowledge. High-dose penicillin or ampicillin, amoxi­
cillin–clavulanic acid, or a second-generation or third-
generation cephalosporin (eg, cefuroxime, cefotaxime, or
ceftriaxone) are often used intravenously. Penicillin,
ampicillin, and ceftriaxone are generally insufficient for
coverage of S aureus, and should not be used in settings
where this microorganism is prevalent. A multicentre,
randomised trial showed that ceftaroline produced
similar clinical response rates to ceftriaxone plus
vancomycin in children with CCAP.126 In areas where
there is a high prevalence of meticillin-resistant S aureus,
vancomycin should be used as an additional first-line
agent until culture results are available. However, one
study in adults suggested that patients receiving a
combination therapy of vancomycin or daptomycin with
an antistaphylococcal β-lactam for bacteraemia caused by
meticillin-resistant S aureus were at an increased risk of
acute kidney injury compared with those who received
standard therapy alone (intravenous vancomycin or
daptomycin) and the trial was terminated.127 Although this
study comprised adults, these results warn of the possible
complications of combination therapy in children. For
children who are allergic to penicillin, clindamycin is an
alternative; however, as with all antibiotic choices,
knowledge of local patterns of bacterial resistance, and
whether any history of allergy (ie, reported allergic
reactions) is real, should be considered. When
M pneumoniae infection is docu­mented, treatment should
also include a macrolide. Macrolides should never be
used as the sole antibiotic in complicated pneumonia.
Ensuring that there is cover against S pneumoniae and
S aureus is important, given the high prevalence of mixed
infec­tions and increasing incidence of macrolide
resistance.128 Coverage of anaer­ obic organisms with
metronidazole should be added for patients with lung
abscesses when aspiration is suspected. Children with
CCAP caused by M tuberculosis should be treated
according to standard guidelines.129 Antibiotics should be
adjusted when the causative pathogen and the pathogen’s
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antibiotic sensitivity become known. If culture results are
negative, any change in prescribed antibiotics depends on
the response of clinical, laboratory, and imaging variables
to the current antibiotic. However, the clinical response in
CCAP is slow, and patience is required before changing
treatment.
The duration of intravenous antibiotic therapy to
prescribe is controversial, and oral antibiotic therapy
should be started as soon as possible.130–132 A course of
2–3 weeks of intravenous antibiotic therapy is usually
sufficient, often with a transition to oral therapy when
fever has abated for at least 24–48 h, there is no respira­
tory distress or evidence of uncontrolled sepsis, the child
is tolerating enteral feeds and has an improved mood
and playfulness, and when inflammatory markers are
reducing.133
There was no difference in treatment failure rates
between children with empyema who were given either
oral or intravenous antibiotics and then discharged
home, but intravenous antibiotics were associated with
more adverse events, which were mostly related to
complications with central lines.134,135
Similar antibiotic coverage is used for most patients
with necrotising pneumonia.136 The effect of the anti­
biotics on persistent fever and severe clinical morbidity,
which are probably driven by the necrotising process
rather than the persistence of infection, is unknown; in
fact, direct cultures of the necrotic material are commonly
negative.121 More pro­longed therapy might be necessary
for lung abscesses, which are typically slow to resolve.
Corticosteroids
The mechanisms of action and the anti-inflammatory
effects of corticosteroids in paediatric respiratory dis­
eases have been reviewed.137 The rationale for the use
of corticosteroids in pneumonia is to treat exuberant
inflammatory responses.138 A Cochrane review including
17 randomised controlled trials (RCTs), of which four
were done with children and had a total of 310 patients,
found that corticosteroid therapy reduced mortality and
morbidity in adults with severe CAP, and morbidity, but
not mortality, in adults and children with non-severe
CAP. In adults, corticosteroid treatment was associated
with more adverse events than treatment with placebo,
especially hyperglycaemia.139
To our knowledge, only one study has evaluated the
effect of systemic corticosteroids in children with CCAP.140
Compared with placebo, dexamethasone resulted in a
shorter median time to recovery, but only in patients with
simple pleural effusion; fewer patients receiving dexa­
methasone needed pleural drainage than patients who
received placebo (9 [30%] of 30 vs 12 [40%] of 30; risk
ratio 0·8, 95% CI 0·4–1·4). At present, systemic cor­
ticosteroids cannot be recommended for patients with
CCAP and more studies are necessary. One systematic
review of corticosteroid therapy in tuberculosis pleurisy
suggested that treatment with corticosteroids decreased
 Review
the time to resolution and the risk of complications, such
as pleural thickening or adhesions, but increased the risk
of adverse events, compared with an antituberculosis
drug regimen.141
Interventional procedures and surgery
Pleural drainage, preferably guided by ultrasonography,
should be done in symptomatic effusions (eg, in patients
with respiratory distress) and in those containing
loculations, unless very small.71,122 Small drains (pigtails)
might be associated with shorter drainage times, fewer
days with fever, and reduced lengths of hospitalisation
than are larger drains.142,143 Compared with drain
insertion, pleural taps can be technically challenging in
children, requiring sedation and resulting in higher re-
intervention rates.144 Rapid drainage of large volumes of
pleural fluid might also lead to re-expansion of
pulmonary oedema.145 Effective analgesia should be
provided until the drain is removed.
Current guidelines do not recommend measuring the
concentrations of lactate dehydrogenase or glucose in
the pleural fluid.71,113,125,146 However, biochemical variables
of pleural fluid have prognostic value: a low pH,
low concentrations of glucose, and high concentrations
of lactate dehydrogenase were predictors of a more
prolonged and complex course of disease in children
with CCAP.147–149
The rationale behind instilling a fibrinolytic agent into
the pleural cavity is to break down fibrin strands to
improve drainage and re-establish pleural circulation.
Several retrospective and observational studies have
shown that intrapleural fibrinolytics (with chest drain)
might result in shorter lengths of hos­pitalisation than
with chest tube drains alone, by both direct comparison
and when intrapleural fibrinolytics are used in patients
who do not respond to drainage.146 The only Cochrane
Figure 5: Adhesions between the visceral and parietal pleura at video-assisted
thoracoscopic surgery
Courtesy of Giovanni Cobellis, Università Politecnica delle Marche, Ancona, Italy.
792 www.thelancet.com Vol 396 September 12, 2020
review on this subject was exclusively about adults.150 In a
double-blind RCT, treatment with intrapleural urokinase
had benefit over treatment with placebo by shortening
hospital stay and reducing the rate of treatment failure
when given in combination with small drains.151 Evidence
for the use of a tissue-type plasminogen activator (eg,
alteplase) in the treatment of empyema in children is
scarce.152 A Canadian multicentre, randomised, placebo-
controlled study153 showed that the addition of DNase to
intrapleural tissue plasminogen activator for children
with pleural empyema had no effect on hospital length
of stay or other outcomes compared with tissue
plasminogen activator with placebo. However, the use of
intrapleural fibrinolytics as a first-line treatment for
paediatric empyema when compared with chest drain
alone needs further scientific validation. Compli­cations
are rarely reported with the use of fibrinolytics in
otherwise uncomplicated empyema, but the risk of
complications is increased in necrotising pneumonia.
Video-assisted thoracoscopic surgery (VATS) debrides
fibrinous material, breaks down loculations (figure 5), and
drains pus from the pleural cavity under direct vision, but
the role of VATS in the primary management of childhood
empyema is controversial. VATS requires specific exper­
tise and is not widely available, especially in low-income
and middle-income countries. In both retrospective and
prospective uncontrolled studies, VATS resulted in an
earlier and more complete resolution of empyema than
did chest tube drainage alone.146 A sys­tematic review of
nine studies of children with empyema showed that VATS
is associated with slightly shorter lengths of hospital stays
and a reduced incidence of re-intervention compared
with chest drain plus fibrinolytics.154 Rare cases of lung
injury, bronchopleural fistula, and even death have been
reported with VATS.155 The use of VATS to treat children
hospitalised with empyema in the USA seems to be
decreasing without an associated worsening of outcomes.156
Thoracotomy, which enables the removal of the
thickened pleural rind and irrigation of the pleural cavity,
is rarely indicated for patients with parapneumonic
effusion and empyema.157 Potential drawbacks include a
large scar, a risk of wound infection, long recovery times,
persistent air leaks, bleeding, and long-term pain. A
mini-thoracotomy involves a similar pro­cedure to that of
a thoracotomy, but done through a smaller incision.
Guidelines from the British Thoracic Society71 and the
American Pediatric Surgical Association146 recommend
that non-operative intervention with fibrinolytics should
be the first-line therapy in complicated parapneumonic
effusion and empyema, because these interventions use
fewer resources than do operative interventions. VATS
should be reserved for patients who do not respond to
non-operative interventions (eg, those who have a
persistent fever, or persistent signs of sepsis or respiratory
distress, or when repeat imaging shows persistent or
increasing intrapleural collections or an organising
phase with peel formation). Raising the threshold for

surgical intervention and using further non-operative
measures can avoid an operation in most children
without increasing in-hospital length of stay.158 We have
suggested a pathway for the evaluation and management
of para­ pneumonic pleural effusion in children with
differing responses to treatment in the appendix (pp 6–7).
In children with necrotising pneumonia, chest drains
are used only if the child also has a large empyema and
should be removed early because of the high risk of
bronchopleural fistula.41,159 Intrapleural fibrinolytics should
be avoided because the breakdown of fibrin might result
in air leaks from peripheral necrotic areas of the lung.121
In a UK survey of 239 children with parapneumonic
effusion, the only factor predictive of a non-response to
fibrinolytic therapy and the need for surgery was the
suspicion of necrotising pneumonia on initial imaging.160
In a retrospective review of 101 children undergoing VATS
for empyema, necro­tising pneumonia was significantly
associated with complications, such as pneumatoceles,
bronchopleural fistula, and prolonged air leaks.161 In
69 children with necrotising pneumonia and concom­
itant pleural effusion, VATS was the most frequent
surgical approach used (12 children [17%]); however,
patients receiving chest drainage alone had similar
outcomes to those managed surgically.41
Image-guided drainage of the cavitation through a
pigtail catheter in combination with systemic anti­
microbial therapy can be used for the treatment of
lung abscesses resistant to antibiotics.162 Thoracoscopic
drainage might be done concurrently with the treatment
of empyema.163 However, the risk of bronchopleural
fistula should be considered. Particularly severe bron­
chopleural fistulas resistant to conservative treatment
might require endobronchial fistula sealing with an
autologous blood patch or a fibrin glue patch, insertion
of a muscle flap into the thoracic cavity, or the attachment
of a Heimlich valve to the drain.164 Pneu­matoceles usually
regress over weeks to months when the infection is
treated, but might require segmental or lobar resection if
they become tense (exceeding more than 50% of the
involved lobe), infected, or rupture into the pleural
cavity.165 However, most giant cysts resolve spontaneously
without the need for surgical interven­ tion.52 Major
surgery should be limited to those few patients with
CCAP who are unresponsive to medical treatment and
interventional procedures.
Supportive therapy
Oxygen and chest physiotherapy
WHO recommends supplemental oxygen in children
with pneumonia who have an oxygen saturation less
than 90%,166 although the British Thoracic Society recom­
mends the higher threshold of 92%.125 However, the
definition of hypoxia depends on altitude. There is
insufficient evidence to show superiority for any methods
of oxygen delivery.167 Oxygen therapy with a high-flow
nasal cannula or continuous positive airway pressure are
www.thelancet.com Vol 396 September 12, 2020 793
Review
used with an increasing frequency in children with
acute respiratory distress, often to avoid the need for
intubation and mechanical ventilation,168 but caution
should be used in general wards.169 An RCT (the COAST
trial) comparing oxygen high-flow nasal cannula and
low-flow oxygen delivery is currently being done in five
hospitals in east Africa.170 There is no evidence to support
the use of chest physiotherapy in children with CAP.171
Fluid and electrolyte replacement
Hyponatraemia (sodium serum concentration <135 mEq/L)
is common among children admitted to hospital with
acute respiratory infections.172 In a retrospective analysis of
medical records, hyponatraemia was found in 104 (33%) of
312 children hospitalised for pneumonia and was associated
with the disease severity.173 The underlying mecha­nisms
causing hyponatraemia are incompletely under­ stood.
In children with CAP, inappropriate antidiuretic hor­
mone secretion occurs only in more severe cases.174
In children requiring maintenance fluid replacement,
isotonic intravenous fluid was associated with a lower risk
of hyponatraemia compared with hypotonic fluid (76 [17%]
of 449 children vs 176 [34%] of 521 children; risk ratio 0·48,
95% CI 0·38–0·60).175 Isotonic fluids should therefore be
used if hydration needs to be maintained in children with
CCAP.
Nutrition
A single retrospective chart review found that a third of
56 children lost at least 5% of their bodyweight during
hospitalisation for parapneumonic effusion, and a fourth
had not regained their previous weight-for-length Z score
measurements 1 month after discharge.176 Hypoalbu­
minaemia was common (35/67) in children hospitalised
with CCAP.177 Nutritional status should therefore be
monitored during and after hospitalisation for children
with CCAP. Hypo­albuminaemia usually improves as the
child recovers and is able to eat normally; there are no
studies showing benefits for nutritional supplementation
in this setting.
Prognosis
Almost all previously healthy children with CCAP
recover completely, and chest radiographs and CT scans
nor­malise or improve markedly by 6–9 months after
discharge (appendix p 8).5,41,50,178 However, delayed life-
threatening tension pneumatoceles can develop in
children discharged home with residual cavitary lesions
following necrotising pneumonia.179 We recommend
that all children with CCAP have regular follow-up
reviews. Those with residual cavitary lesions should also
have a repeat chest radiograph 2–4 weeks after discharge
to ensure that these residual lesions have resolved.
Unlike in adults, mortality due to CCAP in children is
low (<0·5%).178,180 Retrospective studies have found that
pulmonary function is generally normal after CCAP.181,182
Two prospective studies have shown that pulmonary
 Review
function tests returned to normal within a few months
of discharge in children with empyema, and that time to
normalise was independent of treatment.183,184
Prevention
Preventive interventions that are highly effective for
lower respiratory infections in childhood, and are
especially relevant in low-income and middle-income
countries, include national immunisation schedules,
optimising nutrition, avoiding exposure to tobacco
smoke (during pregnancy and childhood), minimising
exposure to indoor air pollution, and strengthening
strategies to prevent the transmission of HIV to children
and to treat those who are infected. However, there is
variation in the effectiveness of preventive interventions
by country, suggesting that no single intervention will
substantially reduce mortality from lower respiratory
infections everywhere. Individual countries or regions
must consider their specific context to identify strategies
to reduce the burden of lower respiratory infections.185
Aspirin and non-steroidal anti-inflammatory agents
should not be used in the context of acute respiratory
infection unless thought to be really essential.
Conclusions
Empyema, necrotising pneumonia, and lung abscess are
serious complications of pneumonia in children. Early
evidence suggests that routine immunisation with the
PCV13 has significantly reduced the burden of CCAP,
without increasing the prevalence of pneumonia due
to other bacteria or non-vaccine serotypes. However,
continued monitoring is essential. S pneumoniae is
the most common bacterial cause of CCAP, despite
substantial advances in the development of pneumococcal
vaccines and the widespread implemen­tation of these
vaccines; however, most data on bacterial prevalence are
from the period before the PCV13 was implemented.
Early detection of CCAP is crucial, and CCAP should be
suspected in all patients with pneumonia who do not
respond to antibiotics after 48–72 h. All CCAPs necessitate
referral to a tertiary centre. Imaging is important in
the evaluation of children with CCAP. Initial imaging
should include chest radiography and ultrasonography,
but chest CT should be reserved only for selected patients.
Microbiological diagnosis of CCAP remains a challenge,
particularly when bacterial pathogens are causative. Blood
cultures should be obtained before the patient initiates
antibiotic treatment, despite the low diagnostic yield, and
prompt pleural fluid analysis should be done where
available. Molecular diagnostic tests are a major diag­
nostic advance. PCR is more sensitive than culture to
detect pathogens in children with CCAP.
High-dose intravenous antibiotics, guided by local
bacteriological knowledge, are the cornerstone of treat­
ment. Evidence-based guidance on choosing the right
antibiotic is scarce. Many patients need only antibiotic
interventions. If pleural drainage is done especially for
794 www.thelancet.com Vol 396 September 12, 2020
a loculated effusion, most clinicians will prescribe
fibrinolytics, although the benefits of such drugs have
not been conclusively proven. VATS and other surgical
procedures are reserved for carefully selected patients
only. In children with necrotising pneumonia and
concomitant empyema, chest drains should be avoided if
possible and removed early because of the high risk of
bronchopleural fistula; fibrinolytics and surgery should
be avoided if possible. Supportive therapy with oxygen
and nutrition is essential for patients with CCAP.
Despite adequate therapy, children with CCAP are often
unwell for several days. This ill health does not imply
treatment failure. However, children with advanced
disease should be evaluated by a multidisciplinary team.
The prognosis of CCAP is usually excellent, with no
clinical, radiological, or lung function consequences in
almost all children. Mortality is rare and usually limited
to patients with previous underlying disease. Families
should be assured of the favourable long-term outcome.
Contributors
FMdB conceived and wrote the first draft of the manuscript. AB, ABC,
AAC, EK, and HJZ reviewed the manuscript for important intellectual
content. All authors approved the final version of the manuscript.
Declaration of interests
ABC reports grants from the National Health and Medical Research
Council, Australia, and fees to her institution from work relating to
being a member of the Independent Data Monitoring Committee of an
unlicensed vaccine by GlaxoSmithKline, and is an advisory member of
study designs for Merck for an unlicensed molecule for chronic cough,
outside the submitted work. All other authors declare no competing
interests.
Acknowledgments
We thank Ines Carloni for reviewing clinical cases and selecting
references.
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