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Community-Acquired Pneumonia in Children
Kenneth McIntosh, M.D.
Community-acquired pneumonia is a common and potentially serious
infection that afflicts children throughout the world; it is fundamentally
different in children and in adults. The annual incidence of
pneumonia in children younger than 5 years of age is 34 to 40 cases
per 1000 in Europe and North America, higher than at any other time
of life, except perhaps in adults older than 75 or 80 years of age.1,2,3,4 In
the developing world, pneumonia is not only more common than it is
in Europe and North America5,6,7; it
is also more severe and is the largest killer of children.8,9
Definitions of pneumonia vary widely. Some require only the presence
of infiltrates on a chest radiograph,2
whereas others require only certain respiratory symptoms or signs.3 The
World Health Organization has defined pneumonia solely on the basis
of clinical findings obtained by visual inspection and timing of
the respiratory rate.10
Definitions are a particular problem in the case of small infants,
since pneumonia and bronchiolitis are both common in this age group,
and the features of these two diseases often overlap. Many studies,
particularly those in the developing world, use the term "acute
lower respiratory tract illness" and make no attempt to
differentiate pneumonia from bronchiolitis.7 For
the purposes of this review, and particularly with respect to
recommendations for treatment, pneumonia will be defined as the
presence of fever, acute respiratory symptoms, or both, plus
evidence of parenchymal infiltrates on chest radiography. Even this
definition overlaps somewhat with that of bronchiolitis and leaves
some room for disagreement among clinicians.
Causes
A very large number of microorganisms can cause childhood
pneumonia (Table 1 and Table 2), and
determining the cause of an individual case may be difficult. The
lung itself is rarely sampled directly, and sputum representing
lower-airway secretions can rarely be obtained from children. In
addition, as is the case in adults, culture of secretions from the
upper respiratory tract is not useful, since the normal flora
includes the bacteria commonly responsible for pneumonia.
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Multiple investigations of pediatric pneumonia during the 1960s and
1970s in North America and Europe emphasized the importance of
infections with respiratory viruses (respiratory syncytial virus,
influenzavirus, parainfluenza viruses, and adenovirus) in preschool
children, Mycoplasma pneumoniae in
school-age children, and Chlamydia
trachomatis in infants between two weeks and four months
of age. Multiple studies have confirmed the capacity of these agents
to cause pneumonia, although their role in individual cases may
sometimes be unclear. More recently, C.
pneumoniae has been found in school-age children with
pneumonia,12,13,14,15
but the strength of arguments for an etiologic role is diluted by
the frequency of asymptomatic infections.16
Similarly, the roles of cytomegalovirus, Ureaplasma urealyticum, Pneumocystis carinii,17
and more recently, rhinoviruses11
as causes of community-acquired pneumonia in otherwise healthy
infants and children remain controversial, in view of the absence of
confirmatory studies or, in some instances, the high frequency of
prolonged carriage or asymptomatic infection — features that make it
difficult to demonstrate a causal role.
The role of bacteria as a cause of severe pneumonia is best documented
in lung-puncture studies, which have been conducted largely in the
developing world.18,19,20,21,22,23,24,25,26
These have confirmed the importance of Streptococcus pneumoniae, Staphylococcus aureus,
and Haemophilus influenzae,
including nontypable strains, as causes of severe pneumonia. In some
studies, S. pyogenes and
gram-negative enteric bacteria also appear.22,23
Other series that have focused on severe or complicated disease,
particularly cases involving parapneumonic effusions, have also
demonstrated the importance of bacteria as causes of pneumonia.27
The precise role of bacteria, particularly in less severe disease,
remains controversial. There have been efforts over the past decade
to define this role more clearly, largely through the measurement of
bacterial antigens, nucleic acid (by means of the polymerase-chain-reaction
assay), antibodies, or immune complexes in blood or urine.11,28,29,30,31,32,33,34,35,36,37
The value of these tests is, however, questionable. Antigen tests
lack specificity,38
and evidence of the sensitivity and specificity of bacterial
antibody tests in children is either absent (in the case of
nontypable H. influenzae and Moraxella catarrhalis) or
severely limited (S. pneumoniae).26
One point is clear: the more tests that are done, the more potential
causes emerge. Two contrasting studies illustrate this point. In one
large, early series, no serologic tests were performed, and mycoplasma
or viruses were identified by culture of respiratory secretions.3 In
only 24 percent of cases was a potential cause identified, and only
0.3 percent involved combined infections. In contrast, a recent case
series included antibody tests for S.
pneumoniae and H. influenzae,
as well as sensitive solid-phase immunoassays for respiratory
viruses and a polymerase-chain-reaction assay for rhinoviruses.11 A
potential cause was identified in 85 percent of cases, and combined
infections, usually bacterial and viral, were seen in 41 percent.
It is not clear what these multiple microbial associations mean.
For example, in spite of the demonstration of possible pneumococcal involvement
(with the use of serologic methods) in 39 percent of hospitalized
children with respiratory syncytial virus infection,39
experience dictates that antibiotics are rarely indicated in the
treatment of such children.40
Although by damaging the respiratory tract, a respiratory virus or M. pneumoniae might facilitate the
aspiration of bacteria into the lungs or the escape of bacterial components
into the lymph or bloodstream, triggering the production of antibody
or immune complexes, this mechanism does not mean that these
bacteria are the cause of pneumonia, nor does it mean, on a more
practical level, that they need to be treated with antibiotics. In
fact, the apparent 35 percent reduction in the incidence of disease
associated with the use of the recently licensed pneumococcal
conjugate vaccine may provide the clearest estimate of the role of S. pneumoniae in causing childhood
pneumonia in Europe and the United States.41,42
In the developing world, bacteria, particularly S. pneumoniae, H. influenzae,
and S. aureus, play a critical
part in causing life-threatening pneumonia, usually with lobar consolidation.
Bacteria are also the chief cause of severe or complicated pneumonias
in children in Europe and North America, although widespread immunization
has nearly eliminated pneumonia due to H.
influenzae type b in the United States. In the future, immunization
may reduce the frequency of pneumonia due to S. pneumoniae. Certain respiratory
viruses, C. trachomatis, and M. pneumoniae are also important
causes of disease in preschool and school-age children. Emerging
evidence indicates that C. pneumoniae
infection may be the cause of a substantial fraction of cases of
pneumonia among school-age children and adolescents.12
Diagnosis
Establishing a microbiologic diagnosis, despite its limitations,
may be important in children with severe or complicated pneumonia or
in those with unusual but treatable causes. A guide to preferred diagnostic
procedures is presented in Table 3. As a
practical matter, however, the cause of pneumonia can usually be
surmised on the basis of clinical and epidemiologic data, findings
on chest radiography, and a few laboratory tests such as a complete
blood count, erythrocyte sedimentation rate, and levels of C-reactive
protein. Although it is difficult to determine the accuracy of
such nonmicrobiologic diagnostic approaches because of the lack of
an etiologic gold standard, there have been many attempts to
correlate them with microbiologic causes. The results of these
attempts have been confusing.
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For example, although the differentiation between typical (i.e., bacterial)
pneumonia and atypical (i.e., viral or mycoplasmal) pneumonia may be
clinically useful in the case of adolescents and adults, these
syndromes are not well defined in infants and preschool children. In
four large series in which investigators looked carefully at the
cause of pediatric pneumonia in relation to clinical or
epidemiologic findings, the signs and symptoms were surprisingly
uniform throughout the etiologic spectrum.34,35,36,43
In one study, pneumonias related to bacterial infection and those
related to viral infection differed only with respect to the
incidence of conjunctivitis (27 percent, as compared with 8 percent)
and otitis media (42 percent, as compared with 22 percent).35
In two other studies, wheezing was found more frequently in patients
with viral pneumonia than in those with bacterial pneumonia (43
percent vs. 16 percent34
and 56 percent vs. 16 percent43),
but the features that we usually associate with viral respiratory
tract infection, such as rhinorrhea, illness in family members, and
myalgia, were not.34,43
When chest radiographs are subjected to blinded readings, they
also cannot be used to differentiate between viral and bacterial disease.
Several studies flatly state that there are no radiologic features
that can be used to differentiate between these two major etiologic
classes.44,45
Another study concludes that radiographic findings have less
discriminatory value than does measurement of C-reactive protein,
erythrocyte sedimentation rate, or the white-cell count and the
differential count.46
In contrast, using data from a large Finnish series, Korppi and his
colleagues47
concluded, as would many radiologists,48
that an alveolar (equivalent to a "lobar") infiltrate is
an insensitive but reasonably specific indication of bacterial
infection. And in cases at either extreme (from typical
bronchiolitis with scattered infiltrates to dense lobar pneumonia
with a large pleural effusion), the level of diagnostic certainty
provided by radiologic findings is quite high.48,49
In addition, there are helpful series that describe the range and
frequency of radiographic findings in patients with mycoplasmal,50
viral,51
chlamydial,52
and pneumococcal53
pneumonia.
Nonmicrobiologic laboratory tests have also been widely used in
an attempt to differentiate bacterial from nonbacterial pneumonia. However,
they are not much better than chest radiographs. Several analyses
show that the C-reactive protein level and the absolute neutrophil
count are the most helpful,46,54,55,56,57,58
although the dividing lines are not sharp. Cutoff levels of 40 mg of
C-reactive protein per liter,56
60 mg per liter,57
and 100 mg per liter46
have been used to identify bacterial infection, each with somewhat
different results. In these comparisons, children with pneumococcal
pneumonia were more easily identified than those with other
bacterial causes, and the findings in patients with mycoplasmal
pneumonia were similar to those in patients with viral infections.46,54
Treatment
Perhaps because of the many controversies that surround the etiologic
process of community-acquired pneumonia in children, there have been
few attempts to devise treatment guidelines in Europe or North
America. In contrast, official recommendations regarding the
treatment of pneumonia in adults have been published in Britain,
Canada, and the United States.59,60,61
An ad hoc group of Canadian experts has published guidelines,62
and numerous recommendations address subgroups of patients with
pneumonia, which are usually classified according to the cause.63,64,65
In contrast, given the enormous problem of undifferentiated pneumonia
in the developing world, the World Health Organization issued its
own treatment guidelines in the early 1980s.10
These guidelines, however, are designed for areas where pneumonia
is a major killer, bacterial pneumonia is probably more common, access
to drugs is limited, and the available diagnostic tools are few.66
Treatment decisions should be based on diagnostic algorithms that
begin with the age of the child, then consider clinical and
epidemiologic factors, and finally take into account the results of chest
radiography. The Canadian consensus statement,62
which is primarily based on age, serves as an excellent introduction
to a discussion of management and treatment.
The most likely causes of pneumonia according to age are given
in Table 4.
Pneumonia during the first three weeks after birth is uncommon, but
when it does occur it is often related to perinatally associated
infections. Between three weeks and three months of age, two of the
most important causes of pneumonia are macrolide-sensitive organisms:
C. trachomatis is also one of the
most common, and Bordetella
pertussis is an infrequent cause of pneumonia, although when
it does occur the disease may be very severe.68,69,70
These pneumonias usually have an interstitial pattern of
infiltrates, with cough as a prominent feature. In children who are
older than five years of age, two other macrolide-sensitive
organisms, M. pneumoniae
and C. pneumoniae, cause
pneumonia that, on chest radiograph, is often not distinguishable
from bacterial pneumonia but that is characterized by cough, a
low-grade fever, and sometimes wheezing. In many surveys, M. pneumoniae is the most common identified
cause of pneumonia among children who are 5 to 15 years of age.
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Despite their limitations, clinical and epidemiologic findings may
be useful. The presence of symptoms and signs of sepsis, even in the
absence of severe respiratory symptoms, suggests bacterial
infection. Localized chest pain (unlike the retrosternal pain of
tracheitis, which tends to occur in viral or mycoplasma infections)
usually signifies pleural irritation, and pleural irritation in an
otherwise healthy child is rarely found in any type of pneumonia
other than bacterial. A child with pneumonia who is wheezing is
likely to have a viral, M. pneumoniae,
or C. pneumoniae
infection.34,43
In most series, conjunctivitis has not been found to be
characteristic of any type of pneumonia except in the case of
infants less than three months of age; in this age group, C. trachomatis infection is included in
the differential diagnosis.71
The presence of otitis media or diarrhea cannot be used to help make
the diagnosis.
Epidemiologic factors are important considerations for the
identification of geographically restricted or exposure-related
pneumonias (Table 1 and Table 2). In
temperate climates, seasonality is a major determinant. Respiratory
syncytial virus infection and influenza are uncommon outside their
winter–spring epidemics. Although M.
pneumoniae epidemics are less predictable, cases do occur
in community-wide clusters during the winter.3,72
There is ample evidence that a chest radiograph is useful to confirm
the diagnosis of pneumonia. Several studies have demonstrated the
lack of both sensitivity73
and specificity74,75
of the findings on history taking and physical examination. The
signs and symptoms that have a high degree of sensitivity (e.g.,
fever and tachypnea) lack specificity, and those with a high degree
of specificity (e.g., rales and pleuritic pain) lack sensitivity.
Chest radiographs that show consolidative lobar infiltrates,
particularly if either a large pleural effusion or any parenchymal
necrosis is present, are indicative of a bacterial cause. When the
white-cell count, differential count, and C-reactive protein level
are very abnormal, they also have predictive value with respect to
bacterial pneumonia and can corroborate a diagnosis that is based on
clinical and historical information.
These considerations, in conjunction with the knowledge of
prevailing antimicrobial-susceptibility patterns, can be used to
determine the necessity for and the nature of empirical drug
treatment (Table 5). In
infants who are 3 weeks to 3 months of age and in those who are 5 to
15 years of age, a macrolide antibiotic is the most reasonable first
choice,69
unless the child appears to have sepsis or the chest radiograph
shows lobar infiltrates (with or without effusion). The choice of
macrolide can be based on availability, cost, tolerability, and
convenience, since in comparative trials they have similar efficacy.15,76 A
second- or third-generation cephalosporin should be used for
children with sepsis, except for infants, who should receive both
ampicillin and gentamicin, as well as a third-generation
cephalosporin in severe cases. Although staphylococcal pneumonia is
now quite rare in Europe and North America,77
it is still a possibility in some instances, and in these
circumstances, oxacillin or, in areas where methicillin-resistant
strains of S. aureus have appeared,78
vancomycin should then be added to the regimen. If the condition of
school-age children does not improve with the use of cephalosporin
or if the findings on the chest radiograph or the clinical findings
are ambiguous, a macrolide should be added, since patients who have
either a M. pneumoniae or C. trachomatis infection can
present with radiographic and clinical findings similar to those
associated with an infection caused by pyogenic bacteria.
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Treatment of pneumonia due to S. pneumoniae
has been the subject of several studies,79,80,81
as well as of consensus guidelines issued by the American Academy of
Pediatrics.64
The emergence of strains of S.
pneumoniae that are not susceptible to penicillin has had
less of an effect on the treatment of pneumonia than on the
treatment of meningitis, and satisfactory rates of recovery can be
achieved with the use of high doses of many -lactam
antibiotics.80
For most nonsusceptible strains, a second-generation cephalosporin (cefuroxime)
or a third-generation cephalosporin (cefotaxime or ceftriaxone) is
somewhat more effective than either ampicillin or penicillin,
although a high dose of amoxicillin (80 to 100 mg per kilogram of
body weight per day) is the preferred treatment for pneumonia in
outpatients. The addition of a beta-lactamase inhibitor conveys no
advantage, since the mechanism of resistance in this organism does
not involve this enzyme. Vancomycin is rarely needed to treat
pneumococcal pneumonia, even severe cases.
Use of the recently licensed pneumococcal conjugate vaccine appears
likely to prevent the majority of cases of pneumococcal pneumonia in
the United States,41
but the high cost of this vaccine will preclude its use in the parts
of the world where pneumococcal pneumonia is most common and severe.
Moreover, there is already some evidence in vaccinated persons that
pneumococcal serotypes not represented in the vaccine are replacing
the serotypes covered by the vaccine and are causing otitis media.82
The World Health Organization's approach to the treatment of
pneumonia, despite its success,83
may well aggravate the problem of antibiotic resistance in communities
that have the highest rates of death from pneumonia. The development
of an affordable pneumococcal vaccine for infants and children
should be a high priority, as should efforts to reduce the risk
factors that lead to a high incidence of severe pneumonia, such as
malnutrition, crowding, and air pollution.
Conclusions
Perhaps because of its etiologic complexity, pneumonia in children
has been relatively refractory to efforts to reduce its incidence and
severity and improve the prognosis. The use of treatment algorithms
in the developing world has led to lower mortality rates,82
but the future of this approach, given the rate of development of
antimicrobial resistance, is uncertain. The wider use of new
pneumococcal conjugate vaccines over the next few years may
represent an important advance in countries that can afford it, but
the public health effects of universal immunization, particularly
over the long run, are not clear. There is still room for
improvements in the diagnosis of pneumonia and in the elucidation of
its cause in individual cases. Finally, regional consensus
guidelines for management and antimicrobial treatment should be
developed, refined over time, and used by practitioners in their
offices and in hospitals.
Supported in
part by a grant from the Bruce and Joline McCaw Fund.
Source Information
From the Division of Infectious Diseases, Children's Hospital, Boston.
Address reprint requests to Dr. McIntosh at Enders 609, Children's
Hospital, 300 Longwood Ave., Boston, MA 02115, or at [log in to unmask].
References
Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.