PAEDIATRIC RESPIRATORY REVIEWS (2006) 7, 145–151

REVIEW

Antibiotics in childhood pneumonia

Katherine A. Hale* and David Isaacsy

Departments of Allergy, Immunology and Infectious Diseases, The Children’s Hospital at Westmead,
Locked Bag 4001, Westmead NSW 2145, Australia

KEYWORDS Summary Pneumonia is one of the most common global childhood illnesses. The
Pneumonia; diagnosis relies on a combination of clinical judgement and radiological and laboratory
Child; investigations. Streptococcus pneumoniae remains the most important cause of childhood
Cntibiotics; community-acquired pneumonia. In addition, viruses (including respiratory syncytial virus)
Streptococcus and atypical bacteria (Mycoplasma and Chlamydia) are likely pathogens in younger and
pneumoniae; older children in developed countries. In the minority of cases only, the actual organism is
Cneumococcal isolated to guide treatment. Antibiotics effective against the expected bacterial pathogens
resistance; should be instituted where necessary. The route and duration of antibiotic therapy, the
Cneumococcal vaccine role of emerging pathogens and the impact of pneumococcal resistance and conjugate
pneumococcal vaccines are also discussed.
ß 2006 Elsevier Ltd. All rights reserved.

INTRODUCTION DEFINITION AND DIAGNOSIS

Pneumonia remains an important cause of childhood
morbidity and mortality worldwide. The annual incidence
of pneumonia in North American and European children
under 5 years of age is approximately 36 per 1000.1,2 Ten
times this rate is seen in developing countries, where
pneumonia is responsible for over 2 million child deaths
annually.3 Pneumonia places an enormous burden on
health services and remains an important global public
health concern. Age, nutritional status and co-morbid
disease have a major impact on microbiological aetiology
and outcome of pneumonia. Increasing antibiotic resis-
tance among common pathogens, the introduction of
new vaccines and medications and changes in medical
practice are altering the epidemiology of pneumonia.
Knowledge of local disease patterns is critical to appro-
priate treatment.
* Corresponding author. Tel.: +61 298453274;
Fax: +61 298453291.
E-mail addresses: katherh2@chw.edu.au (K.A. Hale),
davidi@chw.edu.au (D. Isaacs).
y
Tel.: +61 298453418; Fax: +61 298453421.
1526-0542/$ – see front matter ß 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.prrv.2006.03.011
Pneumonia can be community acquired (CAP) or hospital
acquired (nosocomial). The following discussion relates to
CAP unless otherwise stated. Despite its importance, the
definition and diagnosis of pneumonia remains contentious.
Definitions can be purely clinical4 or may include chest
radiograph (CXR) criteria. There is an overlap between
bronchiolitis and pneumonia, especially in young children.1,5
The diagnosis may be defined in terms of clinical, radiological
or microbiological grounds or a combination thereof.
Clinical
The clinical manifestations can be diverse but classically
include fever, cough and tachypnoea. These symptoms are
often preceded by upper respiratory symptoms such as
rhinorrhoea and low-grade fever.
In young children, it can be difficult to differentiate a
bacterial from a viral aetiology young children as there are
no definitive features. The presence of expiratory grunting,
nasal flaring, fever of over 38.5 8C and auscultation findings
of crackles in a child are suggestive of bacterial pneumonia,
although they are by no means sensitive or specific indi-
146
cators. Wheezing is typically heard in viral or Mycoplasma
infections and not in bacterial pneumonia.
The World Health Organisation algorithm uses tachyp-
noea as a key indicator of pneumonia for areas where there
are no radiological facilities (4). It has a sensitivity of 74% and
specificity of 67% for radiologically diagnosed pneumonia in
children who have been symptomatic for over 3 days.6 The
clinician must remain aware of rarer presentations of pneu-
monia such as chest or abdominal pain as a result of diaph-
ragmatic irritation, fever without focus, or systemic sepsis.
Radiological
CXRs are widely used to evaluate children with fever and
respiratory symptoms, and they are generally thought
useful to confirm the presence and location of a pulmonary
infiltrate. However, which clinical signs indicate the need for
a CXR? One study has suggested that a CXR did not alter
outcome in children with pneumonia in the ambulatory
setting.7 The British Thoracic Society has concluded that ‘it
is advisable to consider a chest X-ray in a child <5 years
with a fever of >39 8C of unknown origin unless classical
features of bronchiolitis are present’.8
There is much disagreement over what specific radiolo-
gical changes constitute pneumonia and whether any changes
are more likely to represent a bacterial, viral or atypical
aetiology. Most, however, would conclude that alveolar
(or ‘lobar’) infiltrates with air space opacification, with or
without air bronchograms, are an insensitive but reasonably
specific indication of bacterial infection.1,9 Pleural effusions
may be associated with bacterial infections (particularly
Streptococcus pneumoniae and Staphylococcus aureus), altho-
ugh rarely with mycoplasmal or viral infections. Viral disease
manifests with a typically bilateral, symmetrical process of
increased peribronchial opacities, hyperinflation from diffuse
small-airway narrowing and subsegmental atelectasis.10
The classical radiographic features of Chlamydia pneu-
moniae, of Mycoplasma pneumoniae, of ‘round’ pneumonias
(most likely pneumococcal) and of tuberculosis (TB) have
been described.11–13 However, there may be no changes
early in disease and there is often intra- and inter-observer
variability in interpretation of the CXR.9
Microbiological
All children admitted to hospital with pneumonia should
have a blood culture. Although the yield is less than 10%, a
positive culture will influence management. A diagnostic
(and therapeutic) pleural aspiration is indicated if a sig-
nificant pleural effusion is present. A nasopharyngeal aspi-
rate for respiratory syncytial virus (RSV) and other
respiratory viruses may be useful in infants and younger
children, to decide whether the child needs antibiotics.
In the majority, a definitive microbiological diagnosis is
not made despite the presence of signs and symptoms
suggestive of pneumonia. When an organism is identified,
K. A. HALE AND D. ISAACS
it is usually by a positive culture of blood, pleural fluid
or lung biopsy, antigen detection or serology.14 A
specific bacterial diagnosis is more likely in severe or
complicated disease in which pleural fluid is sampled and
cultured or blood cultures are positive. The prior admin-
istration of antibiotics may, however, hamper microbio-
logical yield.
Well designed, prospective European and US epidemio-
logical studies documenting aetiology based on serology,
culture, nucleic acid amplification tests and immunofluor-
escence revealed the causative pathogen in approximately
three-quarters of cases.15–18 Streptococcus pneumoniae is
the agent in 27–44% cases of CAP in children. There is a
predominance of viral pneumonia in those under 2 years of
age, and a subsequent decline with age.15,17 Overall, respira-
tory viruses account for 20–45% of all infections.15–17
Mycoplasma pneumoniae and C. pneumoniae have been
classically associated with disease in older, school-aged
children,15,17 although a study from Michelow et al.16
showed the mean age of Mycoplasma and Chlamydia infec-
tion was 5 years and 35 months respectively.16
Staphylococcus aureus, Moraxella catarrhalis and group A
streptococci, Streptococcus milleri and Haemophilus spp.
were uncommonly identified.16 Haemophilus influenzae
type b has virtually disappeared from immunised popula-
tions.5 Mixed infections were present in 9–30% of patients,
most commonly Streptococcus pneumoniae in association
with a respiratory virus, Mycoplasma or Chlamydia.15,17,18
Hospitalised patients had more documented Streptococcus
pneumoniae, viral and mixed infection.16,18
Most viral and bacterial infections are seasonal, and the
epidemiology can be important in analysing data and
deciding on treatment. Both M. pneumoniae and Bordetella
pertussis cause epidemics every 3–4 years, so short-term
studies may under- or overemphasise their importance
depending on whether or not an epidemic is included in the
study. Antibiotic treatment for these organisms is more
important during their season.
Improvements in diagnostic techniques such as the
polymerase chain reaction (PCR) continue. In recent times,
PCR tests for Streptococcus pneumoniae, M. pneumoniae, B.
pertussis and Chlamydia spp. have been developed,
although they are not currently widely available outside
referral centres.19 A rapid immunochromatogenic urinary
antigen detection kit (Binax NOW; Portland, Maine) for
pneumococcus has been developed. There have been
promising results in adults with pneumonia, but the test
seems unlikely to be useful in childhood pneumonia
because high carriage rates make the significance of a
positive test uncertain.20,21
Mycobacterium tuberculosis can cause pneumonia either
by bronchial compression due to hilar lymphadenopathy
in primary TB, or by causing tuberculous bronchopneumo-
nia in disseminated TB or in post-primary TB.13 TB should
always be considered in the differential diagnosis of pneu-
monia in developing countries. In industrialised countries,
ANTIBIOTICS IN CHILDHOOD PNEUMONIA
TB should be considered where there are suggestive clinical
features (e.g. recurrent or persistent collapse of one lobe),
radiological features (hilar lymphadenopathy, calcification and
cavitation) or epidemiological features (ethnicity, exposure).
Neonatal pneumonia may be part of early onset sepsis
due to group B Streptococcus or Listeria monocytogenes
infection.5 Cytomegalovirus and Gram-negative enteric
bacilli can also cause pneumonia in this age group. Atypical
organisms such as Chlamydia trachomatis and B. pertussis are
possible pathogens in newborns and young infants, in
addition to pneumococcus and respiratory viruses.5
Emerging pathogens
PCR testing for human metapneumovirus has recently been
developed. The exact contribution of this virus to child-
hood pneumonia remains to be fully elucidated, but recent
studies suggest that about 12% of episodes of lower
respiratory tract infection in infants may be due to this.
In one study, 59% of human metapneumovirus cases were
classified as bronchiolitis and 8% as pneumonia.22
Rates of infection with community-acquired methicillin-
resistant Staphylococcus aureus infections, including pneu-
monia and pleural empyema, are increasing.23,24 These
organisms tend to be less resistant to antimicrobial agents
than are hospital-acquired strains of methicillin-resistant
Staphylococcus aureus (MRSA).23 In addition, many contain
the gene for Panton–Valentine leukocidin, a toxin that has
been associated with clinical features of serious disease
including necrotising pneumonia, abscess and empyema
formation and respiratory failure.23
Influence of pneumococcal vaccine
The introduction of the heptavalent conjugate pneumo-
coccal vaccine has dramatically reduced rates of invasive
pneumococcal disease in the USA and parts of Europe.25
Early reports suggest a significant reduction in pneumonia
predominantly in young children26 and a decrease in
pneumococcal empyemas.24
In the Gambia, a randomised, double-blinded, placebo-
controlled trial showed the nonavalent vaccine was highly
effective against radiological pneumonia but funding to
make the current vaccine readily available to African
children remains an obstacle.27 Studies have shown a
reduction in the number of antibiotic-resistant pneumo-
coccal infections, as expected because the serotypes most
commonly associated with antibiotic resistance are con-
tained in the vaccine. Evidence to support concerns about
disease due to replacement with other pneumococcal
serotypes has not yet materialised,26 although ongoing
surveillance is imperative.
Other laboratory parameters
Investigations often performed in children with pneumonia
in industrialised countries include total white cell count
147
and differential; inflammatory markers such as erythro-
cyte sedimentation rate and C-reactive protein; and
procalcitonin. Although a raised white cell count of over
15% 106/l with a predominance of band forms and an
elevated C-reactive protein level may favour a bacterial
aetiology, the sensitivity and specificity of these tests is
highly variable.28 Some centres do not recommend
routinely measuring them as they usually do not affect
management.
In conclusion, the initial diagnosis of pneumonia is usually
based on clinical suspicion, which may be confirmed with
characteristic radiological and possibly laboratory features.
Not all features are present in any one child, and the
emphasis on individual features may vary with age and
likely aetiology. A good working knowledge of local micro-
biology is essential prior to making any decisions about
antibiotic therapy.
ANTIBIOTIC TREATMENT
Once the above parameters have been considered, a deci-
sion has to be made on whether empirical antibiotics are
indicated, and if so which ones. Antibiotics may be withheld in
the non-toxic child in whom signs and symptoms suggest a
viral aetiology and a CXR is not usually necessary. These
children should be reviewed regularly. Rapid immunofluor-
escence testing for respiratory viruses is useful.
It is usually safe not to give antibiotics in RSV disease,
although approximately 20% of children with suspected
viral pneumonia ultimately receive antibiotics.29 As pre-
viously mentioned, a minority will have mixed infections.
Bacteraemia is rare in RSV infection, although it is more
common if there is underlying congenital heart disease, if
the RSV has been nosocomially acquired or if intensive care
admission is needed.30
In childhood CAP, an agent effective against pneumo-
coccus is required in the first instance. In developing
countries, where cost is a primary consideration, co-
trimoxazole is still recommended as first-line empirical
therapy but there are increasing concerns about resis-
tance.31 Amoxicillin is a reasonable first choice for the
empirical oral therapy of bacterial childhood CAP in
industrialised countries.5 Amoxicillin has the advantage
over penicillin V of administration three times daily and is
better absorbed than ampicillin; it is also well tolerated
with few side-effects.
Options for penicillin-allergic patients include co-trimox-
azole, macrolides (e.g. erythromycin or azithromycin) if
local pneumococcal resistance is low or an early-generation
cephalosporin (e.g. cephalexin) if the penicillin reaction
was not anaphylactic (approximately 10% risk of cross-
reactivity).32 A macrolide should be administered if a
diagnosis of atypical pneumonia is suspected. In the past
10 years, new ‘second-generation, macrolides have
emerged, for example azithromycin and clarithromycin.
Advantages of the newer medications include their broad-
148 K. A. HALE AND D. ISAACS

spectrum activity, less frequent dosing regimen compared
with erythromycin and virtually equivalent efficacy; they
do, however, cost more.33,34
Which children require admission to hospital with or
without parenteral treatment? Few randomised trials have
examined this question. Oral antibiotics are usually con-
sidered sufficient in children who are older than 6 months
and not toxic, dehydrated or requiring oxygen, in whom
compliance can be guaranteed. A recent large randomised
trial in developing countries suggested that oral amoxicillin
was equivalent to injectable penicillin for the treatment of
severe pneumonia by World Health Organization defini-
tions (chest indrawing). Treatment failure was predicted by
age (3–11 months), degree of tachypnoea and hypoxia.35
Oral amoxicillin was equivalent to injectable procaine
penicillin in the early treatment of children with radio-
graphically defined pneumonia deemed well enough for
outpatient treatment.36
If parenteral therapy is required and pneumococcus is the
likely pathogen, benzylpenicillin or an aminopenicillin can be
used. Broader-spectrum agents have no additional benefit.37
For the severely unwell, toxic child with or without effusions,
where rarer pathogens are a possibility, therapy should
include a third-generation cephalosporin (e.g. ceftriaxone)
with a macrolide if atypical agents are potential pathogens, or
a penicillinase-resistant beta-lactam (e.g. oxacillin) or vanco-
mycin if Staphylococcus aureus or MRSA infection is likely. A
summary of appropriate therapy is shown in Table 1.
Duration of treatment is another contentious issue
that has not been well examined. If admitted to hospital,
most children can safely receive 1–2 days of antibiotics
intravenously before switching to oral therapy.38 Longer
stays may be attributed to mixed viral/bacterial infec-
tions.39 Consensus opinion suggests a period of time of
oral therapy following intravenous; although the exact
duration has not been well defined, a period of 5–10 days
is usual.
Pneumococcal resistance
Pneumococcal isolates not susceptible to penicillins and
third-generation cephalosporins have been well described
in vitro, and rates between 10% and 40% have been
reported from worldwide surveillance.40 There is significant
geographical variation, with high rates in Spain, France and
parts of south-east Asia and the USA.

Table 1 Suggested antibiotic treatment of paediatric community acquired pneumonia

Age Distinguishing CXR Likely Suggested treatment
clinical features features aetiology Oral Intravenous
3 weeks to Afebrile, Interstitial Atypical Erythromycin (40 mg/kg/day Rarely required Erythromycin
3 months dry cough, in 4 divided doses) or (40 mg/kg/day in
not toxic Azithromycin (1 dose of 4 divided doses)
10 mg/kg/day, then
5 mg/kg/day for 4 days)
3 months to Wheeze No alveolar Viral Supportive
5 years consolidation
or effusion
Any age Alveolar S. pneumoniae Amoxicillin Benzylpenicillin (120 mg/kg/day
>3 monthsa consolidation (80–100 mg/kg/day in 4 divided doses) or
in 3 divided doses) Ampicillin (200 mg/kg/day
in 4 divided doses)
Any age Severely Effusion S. aureus Penicillinase resistant
>3 monthsa unwell or beta lactam (e.g. Oxacillin)
toxic child or vancomycin
(if MRSA suspected)
Less common 3rd generation cephalosporin
pathogens (e.g. Cefotaxime 200 mg/kg/d
e.g. Moraxella in 3 divided doses)
catarrhalis,
Haemophilus spp.
>5 yearsb Dry cough, Variable Atypical Erythromycin (40 mg/kg/day Erythromycin (40 mg/kg/day
crackles or in 4 divided doses) or in 4 divided doses) or
wheeze Azithromycin (1 dose Azithromycin 5 mg/kg/day
of 10 mg/kg/day, then in 2 divided doses)
5 mg/kg/day for 4 days)
a
If unable to easily differentiate between pneumococcal and atypical; start treatment for both until diagnosis clearer.
b
Atypical disease may rarely present younger than 5 years.
ANTIBIOTICS IN CHILDHOOD PNEUMONIA
The main mechanism of resistance is via the alteration of
penicillin-binding proteins, which can be overcome by
achieving adequate local drug levels; i.e. it is a decreased
sensitivity rather than an absolute resistance. There is as yet
no evidence of clinical treatment failure of infections out-
side the central nervous system using high-dose penicillin or
third-generation cephalosporins.41 Hence amoxicillin or
penicillin remains the antibiotic of choice in pneumococcal
pneumonia. However, in the rare scenario of high pneu-
mococcal penicillin resistance (mean inhibitory concentra-
tion >2 mg/l), most clinicians would change to a
cephalosporin (if sensitive) or add vancomycin.
Pneumococcal macrolide resistance is mediated via
alteration of the 50S ribosomal binding site, thereby
preventing binding and the subsequent inhibition of bac-
terial protein synthesis. A second mechanism is via the
presence of efflux pumps for the antibiotic. It is often
associated with penicillin non-susceptibility.42 Rates of
usage and resistance of the newer macrolides have sub-
stantially increased over recent times and vary by geo-
graphical region. There are reports of treatment failure of
pneumococcal disease using macrolides alone; thus, this
approach is not recommended.42
NOSOCOMIAL PNEUMONIA
Nosocomial pneumonia is a relatively common infection in
children and can cause significant morbidity. Risk factors
include admission to an intensive care unit, intubation,
burns, surgery and underlying chronic illness. Gram-nega-
tive bacilli, including Pseudomonas aeruginosa, Enterobacter
spp. and Acinetobacter spp., are important causes, as are
Staphylococcus aureus and respiratory viruses such as RSV.43
There is geographical variation in the predominance of
certain organisms and resistance patterns, and again local
knowledge is essential.44,45 Antibiotic therapy should be
directed towards these main pathogens; a suitable agent
might be a broad-spectrum penicillin with beta-lactamase
inhibitor and anti-pseudomonal activity, for example ticar-
cillin/clavulanic acid.44
OVERUSE AND MISUSE OF
ANTIBIOTICS
Narrow-spectrum antibiotics are advocated in the first
instance. Inappropriate use of antibiotics can result in
treatment failure and adverse drug reactions, and contri-
bute to emerging pathogen resistance.46 Consideration of a
drug’s pharmacodynamic and pharmacokinetic properties is
also important. Agents with low maximum plasma or tissue
concentrations and long half-lives may be more likely to
expose bacteria to resistance-selective concentrations. The
strategy of administration is also important; low doses of
beta-lactams and long treatment duration are risk factors
for the carriage of pneumococci non-susceptible to peni-
cillin, whereas short-course, high-dose therapy minimises
149
this risk.47 Convenience and tolerability are also essential
considerations in paediatrics.
PROTOCOLS
There are several published guidelines4,8 directing the
treatment of pneumonia. It is not known whether these
are routinely followed. Locally produced guidelines have led
to better prescribing habits.48 A simple measure such as the
introduction of prescribing cards has been shown to influ-
ence prescribing habits and to be cost-effective.49 It is not
known whether this affects patient stay and outcome,
although a report in adults suggests that it may.50
PRACTICE POINTS

A sensible approach to the child with pneumonia is
based primarily on clinical criteria to judge aetiol-
ogy and severity of disease.

Further investigations may be necessary depend-
ing on the confidence of the diagnosis and the
severity of the disease.

Appropriate antibiotic treatment, for example as
outlined in Table 1, should be instituted if neces-
sary.

The antibiotic spectrum should be as narrow as
possible.

Amoxicillin or penicillin for 5–10 days remains the
treatment of choice of pneumococcal pneumonia.

In most cases, the child will be well enough to be
discharged home with a relatively short duration of
therapy.

Admission to hospital usually necessitates intrave-
nous treatment and/or oxygen therapy and is
necessary for those who are particularly toxic or
have complications.

We await further data on the influence of the
pneumococcal conjugate vaccine on the preva-
lence of this disease.
RESEARCH DIRECTIONS
Many features of diagnosis and treatment of one of
the most common conditions encountered in pae-
diatric practice remain cloaked in uncertainly. Specific
areas needing more research include:

The utility of the chest X-ray.

Oral or intravenous treatment for moderate-to-
severe disease.

The total duration of treatment.
150
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