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Worldwide, community-acquired pneumonia is a leading cause of
infectious morbidity and mortality in children.1Studies
that employ blood culture, serology, and polymerase chain reaction,
as well as those that use pneumococcal conjugate vaccines as a probe
to determine the proportion of disease due to Streptococcus
pneumoniae, suggest that pneumococcus is the major pathogen
in community-acquired pneumonia in children, frequently in the presence
of concurrent viral respiratory infection. Several observations
such as the presence of patchy perihilar infiltrates
on x-ray suggests that most cases of bacterial pneumonia result
from aspiration of nasopharyngeal organisms and provide the rationale
that respiratory tract flora, nontypeable Haemophilus influenzae,
Streptococcus pyogenes, Moraxella catahhralis, Staphylococcus aureus, and S pneumoniae are
the major bacterial pathogens in pediatric pneumonia.
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Community-acquired pneumonia is most common in infants and toddlers.
In children ages 6 months to 5 years, the incidence is 40/1000
patients/year with declining frequency with increasing
age.2 Further analysis of the incidence of pneumonia
in children < 5 years of age identifies a peak incidence of 52.3/1000
children/year at 2 to 5 years of age with slightly lower
incidence rates in children < 24 months.3 Mortality due
to community-acquired pneumonia is low—0.1/1000
patients/year in children aged < 15 years. Males are
affected almost twice as commonly as females.4 Socioeconomic
status and ethnicity affect pneumococcal pneumonia rates, with a
greater risk of pneumonia in US children aged < 5 years of Asian,
African American, or Hispanic ethnicity compared with those of Caucasian
ethnicity.3 Seasonal variations show a greater
frequency in the winter and spring months,2,6,7 and
during peaks of respiratory syncytial virus (RSV), influenza A,
and, in older children, Mycoplasma pneumoniae.2 Mortality
due to community-acquired pneumonia, as reported from Finland, is
low—0.1/1000 patients/year in children
aged < 15 years. Gender differences are also observed, with males
having a rate nearly double that of females (47.4 vs 23.6/1000
patients/year in Finland).4 Differences
in incidence are also reported by socioeconomic status and ethnicity.
Rates of pneumococcal pneumonia are higher in native Alaskan children
than in nonnatives.5A greater risk of pneumonia
in US children aged < 5 years of Asian, African American, or
Hispanic ethnicity compared with those of Caucasian ethnicity has
also been observed.3 The incidence of community-acquired
pneumonia also varies by season; studies in the United States2,6 and
Israel7 report greater frequency in the winter
and spring months. Annual peaks of respiratory syncytial virus (RSV),
influenza A, and, in older children, Mycoplasma pneumoniae,
infection also are associated with higher pneumonia incidences.2Hospitalization
for all cause community-acquired pneumonia is greatest in children
less than 2 years of age and represents about 10% of all
pneumonia cases in that age group.8
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Lower respiratory tract infections (RTIs) are both more frequent
and associated with a greater mortality in developing countries.
The incidence among children ages 0 to 5 years from 10 developing
countries is estimated to range from 0.2 to 8.1 new episodes/100 child-weeks
at risk.9 Mortality from pneumonia has become uncommon
in developed countries,4,10,11 yet remains a major
cause of death in developing countries.12 In 1990,
respiratory infections were the third most common cause of death
worldwide; 90 percent of deaths occurred in developing countries.12 Nearly
70% of deaths are in children less than 4 years old.
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Microbiological Etiology
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Community-Acquired
Pneumonia
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A large spectrum of pathogens have the capacity to cause community-acquired
pneumonia in children (Table 240-1). In 20% to 60% of
cases, no pathogen is isolated.13,14 Viruses such
as respiratory syncytial virus, influenza virus, parainfluenza viruses,
and adenovirus are often recovered from the upper or lower respiratory
tract, especially in younger children but this does not preclude the
presence of a bacterial etiology as well. Blood culture is frequently
negative, and sputum or tracheal secretions are rarely obtained
in the peak age ranges for pediatric pneumonia. In ambulatory children
in both the United States (n = 168)15 and
Finland (n = 201),16 viral
pathogens were recovered from 28% to 37% of patients
< age 4 and less frequently from children ages 5 to 9 (10–21%)
or 9 to 16 (0–4%).
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++
Studies of vaccine efficacy have provided important insights
into the role of bacterial pathogens in the etiology of pediatric
pneumonia. Following universal immunization of infants with the
7-valent pneumococcal conjugate vaccine (PCV), a decline of 40% in ambulatory
pneumonia and 50% in hospitalization for pneumonia in children
less than 2 years old was reported.8 Zhou reported
a decline of 40% in ambulatory pneumonia, and 50% in
hospitalization for pneumonia in all children less than two years
of age. The implied role of Streptococcus pneumoniae as
the etiology in these proportions of cases exceeded expectations.
Black and colleagues have reported a decline of 35% in
pneumonia characterized by an abnormal chest x-ray in children immunized
with 7-valent PCV compared to controls. Klugman and colleagues observed
an approximate 40% decline in hospitalized pneumonia associated
with influenza, respiratory syncytial virus, and human metapneumovirus
pneumonias in South African children immunized with 9-valent PCV compared
to controls, providing further support for an expanded role of S
pneumonia as a pathogen in a large proportion of cases
of pneumonia in children.3,17 Furthermore, experimental
serologic methods provide evidence of pneumococcal infection in
almost 30% of cases of pneumonia across all age groups,
indicating that S pneumoniae plays an etiologic
role in many young children with acutely abnormal chest x-rays and
clinical symptoms or signs of respiratory tract infections that
do not have concurrent bacteremia, empyema, or consolidated lobar
pneumonia.15,16 Furthermore, experimental serologic
methods used to evaluate children with pneumonia provide evidence
for pneumococcal infection in approximately 28% of cases
across all age groups.15,16 These data support
a role for Streptococcus pneumoniae as the etiology
of pneumonia beyond those identified by concurrent bacteremia and beyond
those with empyema or consolidated lobar pneumonia to include as
many as one third of young children with acutely abnormal chest
x-rays and clinical symptoms or signs of respiratory tract infections.
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Additional bacterial pathogens are also important causes of pneumonia
in children. S pyogenes is associated with rapid
onset of large pleural effusions, prolonged fever, and significant
toxicity. H influenzae type b (Hib), prior to the
introduction of Hib conjugate vaccine and in countries where Hib
vaccination has not been incorporated into national immunization
programs, and possibly nontypeable (NTHi) strains, are frequent
causes of pneumonia. A substantial role for NTHi is supported by
results of lung aspirate studies from the Gambia and Papua New Guinea,
where nontypeable strains are recovered from 25% to 53% of
children with Haemophilus pneumonia18 (see eTable 240.1). Most recently, S aureus,
specifically community-acquired methicillin-resistant (CaMRSA) isolates,
have reemerged as an important cause of complicated pneumonia. On
autopsy these cases frequently demonstrate microabscess and hemorrhage.
Cavitation, pleural empyema, pneumatocele, bronchopleural fistula,
and/or pyopneumothorax can complicate staphylococcal pneumonia.
Karen and colleagues reported S aureus as the most
common cause of pleural empyema in children in the decade between
1993 and 2002.19
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The atypical/intracellular pathogens, Mpneumoniae and Chlamydophila (Chlamydia) pneumoniae, are
recognized as important pathogens causing community-acquired pneumonia
in children. Both are difficult to culture; therefore, most studies
rely on nonstandardized serological tests or polymerase chain reaction.20,21 Studies
of children with ambulatory pneumonia identify M pneumoniae infection
in 26.5% to 29.5% of cases and of C pneumoniae in 15.0% to
28.5% of cases. These atypical/intracellular pathogens
are found most commonly in children aged > 5 years; however, they
also occur in younger children as shown by a recent study in which
community-acquired pneumonia in children less than age 5 years was
due to Mycoplasma pneumonia in 15% of
cases, and to Chlamydia pneumoniae in 9% of
cases (see eTable 240.2).22,23 Data
from a recent study did not find the proportion of children infected
with M pneumonia or C pneumoniae to
be age related.
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Hospitalized
Children
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Becausehospitalized children are usually younger,
have more complicated pneumonia, or are more severely ill, the microbiology
in such children differs somewhat from ambulatory patients. The
incidence of respiratory syncytial virus and human metapneumovirus
is higher in young children, and concurrent infection with pneumococcus
appears to be common based on results of studies described earlier.24,25 In
children with complicated bacterial pneumonia with necrosis and/or
empyema, S pneumoniae and both methicillin-sensitive
and methicillin-resistant S aureus are dominant.
Other less common bacterial pathogens recovered from hospitalized
children with pneumonia include group A β-haemolytic
streptococci, H influenzae, and M catarrhalis.Perinatally
acquired Chlamydia trachomatis pneumonia, a once
common etiology of pneumonia in the first 2 months of life, has
been largely eliminated in developed countries through the systematic
screening and treatment of pregnant women. Infection with H influenzae type
b has been virtually eliminated following immunization with Hib
conjugate vaccine in the United States; however, both C trachomatis (in
infants) and H influenzae type b may still be significant
pathogens in developing countries.26,27Mycobacterium
tuberculosis may also present as an acute pneumonia with fever, respiratory
signs, and alveolar infiltrate with or without pleural effusion.
Tuberculosis should be considered in children who recently immigrated to
the United States, those returning to travel from countries with
endemic tuberculosis, and those who have had contact with recently
diagnosed individuals. Skin testing for tuberculosis should be a
routine part of evaluation of children with pneumonia.
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Clinical Presentation
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Clinical signs and symptoms of bacterial pneumonia overlap with
many aspects of viral pneumonia preventing clear discrimination between
the two. Fever, frequently greater than 102°C ill appearance, and
respiratory and/or abdominal signs are found in the majority
of patients with both RSV pneumonia and pneumococcal pneumonia (see eTable 240.3).28 Tachypnea and rales/crackles
are reported in 40% to 50% of patients.29 Bacteremic
pneumonia is more frequently associated with greater severity of
clinical signs and symptoms such as higher fever.
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Radiological Examination
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Chest x-ray is often used to confirm the presence of pulmonary
infiltrates/consolidation in patients with suspected pneumonia.
In some studies, the presence of infiltrates was part of the definition
of pneumonia.1 Although x-ray will confirm the
presence of pneumonia in most children, data concerning its usefulness in
establishing the microbial etiology is conflicting. Several studies
suggest that the presence of alveolar infiltrates is an insensitive
but reasonably specific indicator of bacterial infection.28,29 In
one Finnish study of hospitalized children with pneumonia (n=254),
71% of those with alveolar infiltrates had bacterial infections.29 More
recent studies (eTable 240.4) find no significant
correlation between the radiological picture and the etiological agent—ie,
it was not possible from the chest x-ray to conclude whether the
child had viral infection, bacterial infection, or mixed infection—but
rather a correlation between age and radiographic findings (see eTable 240.4).30
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++
Results from efficacy studies of 7-valent pneumococcal conjugate
vaccine and Hib conjugate vaccine demonstrate the greatest benefit
in prevention of lobar infiltrates, confirming that most often these
infiltrates represent pneumococcal pneumonia.3 Some findings
on x-ray are useful for the diagnosis of bacterial pneumonia. The
presence of necrotizing pneumonia (pneumatocele, loculated empyema,
and/or necrotic lung tissue) are virtually diagnostic of
pneumococcal or staphylococcal disease. Studies from 1990 through
2000 indicated that S pneumoniae was the more common
etiology in cases with complicated pneumonia but recently the incidence of
disease due to S aureus has increased.19 Although
studies from 1990 through 2000 would have supported Streptococcus
pneumoniae as the more common etiology in cases with complicated
pneumonia, more recently an increase in disease due to Staphylococcus
aureus has been observed.19
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Laboratory Tests
to Discriminate Viral from Bacterial Pneumonia
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Determining the etiology of pneumonia in children is challenging
because bacteremia is uncommon, pleural effusion is present in only a
small percentage of children, antimicrobial therapy has often been
administered prior to collection of fluid, nasopharyngeal cultures are
not necessarily representative of lower respiratory tract secretions,
and the vast majority of children do not produce sputum.31 More
aggressive procedures, such as lung puncture and bronchoalveolar
lavage, may be diagnostic but are generally reserved for hospitalized patients
with significant respiratory distress and therefore only inform
us about a selected population of children with pneumonia.
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Acute-phase reactants such as total and differential white cell
count, erythrocyte sedimentation rate, C-reactive protein, and procalcitonin
have been evaluated for their usefulness in discriminating between
viral and bacterial etiologies.32,33 In general,
these markers of inflammation demonstrate weak correlation with
etiology with poor sensitivity and specificity. Clinically such
testing has a limited role in establishing a diagnosis in children
with pneumonia.
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Serological tests have been evaluated for diagnosis of pneumonia
due to S pneumoniae, M pneumoniae, and C
pneumoniae.34,35 These tests detect specific
immunoglobulin (IgM or IgG) by a number of different techniques against
bacterial antigens specific for each of these pathogens. In general,
many of the tests are moderately specific, have wide variation in
sensitivity, lack reproducibility, and have not been standardized.36-38 In
addition, serological tests provide only retrospective diagnosis
because they require comparison of acute and convalescent serum.
++
Polymerase chain reaction tests have received increasing attention
in the last few years. Potentially DNA from S pneumoniae, M
pneumoniae, and C pneumoniae can be detected
in clinical samples from children with acute pneumonia. Recent studies
support the potential of polymerase chain reaction for detecting
pneumococci in nonbacteremic pneumococcal pneumonia in children.38 However, further
evaluation is necessary to establish their sensitivity, specificity,
and reproducibility, and consensus assays need to be established
before clinical use can be entertained.