Definitions of Specific Infections

Defining pneumonia in critically ill infants and children

Joanne M. Langley, MD; John S. Bradley, MD

Objective: To define pneumonia in critically ill children in the
intensive care unit setting for surveillance of infection and for the
design, conduct, and evaluation of clinical trials in the prevention
and therapy of lower respiratory tract infections in this popula-
tion.
Design: Summary of the literature with review and consensus
by experts in the field.
Results: A variety of diagnostic criteria from the medical
literature, professional societies, and governmental health agen-
cies and regulators were identified. Very few of these diagnostic
criteria have been validated for use in children. We propose
definitions for definite, possible, and probable pneumonia that
build on identified definitions in the literature and use combina-
tions of symptoms, signs, and laboratory criteria. Gaps in knowl-
edge were identified.
Conclusions: Although pneumonia is one of the most common
diagnoses in critically ill children, there have been few studies
validating diagnostic criteria. Definitions for definite, probable, and
possible community-acquired pneumonia and nosocomial pneumo-
nia were achieved by consensus of experts based on guidelines from
governmental agencies, professional organizations, and published
literature. Future research should determine the utility of these def-
initions in the critically ill child and adapt them accordingly. (Pediatr
Crit Care Med 2005; 6[Suppl.]:S9 –S13)
KEY WORDS: ventilator-associated pneumonia; infection; inten-
sive care; children

W orldwide, acute respira-
tory tract infection is the
most common cause of
death in children (1). Al-
though childhood mortality rates from
pneumonia have decreased by up to 97%
during the last 50 yrs (2), pneumonia is
still common, occurring in 34 to 40 cases
per 1,000 children in North America and
Europe (3). Both community- and hospi-
tal-acquired pneumonia may cause life-
threatening illness in children, resulting
in the need for management in an inten-
sive care unit (ICU) setting. To determine
the most efficacious treatments for pneu-
monia in critically ill children through
clinical trials, conduct surveillance in
ICU settings, and apply that knowledge in
the practice setting, it is essential that
consistent and meaningful descriptions
of pneumonia be used. We offer some
considerations for defining pneumonia in
From the Clinical Trials Research Centre, IWK
Health Center, and the Department of Pediatrics, Dal-
housie University, Halifax, Canada (JML); and the Chil-
dren’s Hospital and Health Center and the University of
California, San Diego, CA (JSB).
This work was supported by the Mannion Family
Fund—Center for the Critically Ill Child, Division of
Critical Care Medicine at Children’s Hospital Boston,
the PALISI Network, and the ISF.
Copyright © 2005 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000161932.73262.D7
this patient population, review available
diagnostic criteria, and propose defini-
tions. These proposed definitions could
be modified over time as their accuracy is
evaluated through validation in clinical
studies.
Defining Pneumonia: What
Clinical Problem Are We Trying
to Capture?
Lower respiratory tract (LRT) infection
can be considered as infection occurring at
an anatomic level below the vocal cords (4),
which would include the clinical syn-
dromes of bronchitis, bronchiolitis, and
pneumonia and its complications. We re-
strict our discussion to pneumonia. In clin-
ical practice, pneumonia has several de-
scriptions based on clinical presentation,
pathophysiology, and site of infection
within the lung, roughly correlating with
the etiology. We consider these clinical syn-
dromes together under the label pneumo-
nia, which is an infection of the lung.
Considerations in the Diagnosis
and Definition of Pneumonia in
the Critically Ill Child
For decades, a reproducible, accurate
definition of pneumonia has been sought
by physicians who care for adults and
children. Making a diagnosis has been
described as “the process of recognizing
the class or group to which an illness
belongs so that, based on our previous
experience with the class, the subsequent
clinical acts we can afford to carry out
will maximize the patient’s health” (5). A
diagnosis is a hypothesis rather than a
certainty, the purpose of which is to allow
us to make optimal clinical decisions (6).
The obstacles to accurate diagnosis and
definition of pneumonia in the critically
ill child are well known but worth review-
ing briefly here.
The respiratory tract is one continu-
ous system that connects the ear, eusta-
chian tube, pharynx and mouth, sinuses,
nares, and upper and lower respiratory
tracts. The upper respiratory tract is nor-
mally colonized with nonpathogenic or
“commensal” bacterial flora, but physical
and immunologic host defenses generally
ensure that bacteria that gain access to
normally sterile sites (e.g., the LRT) are
cleared. The “gold” or “criterion” stan-
dard for pneumonia is microbiological
identification of a pathogen from a LRT
specimen (4). LRT specimens are difficult
to obtain, may require invasive proce-
dures, and are challenging to obtain in a
manner that samples only the LRT with-
out contamination from colonized sur-
faces of the upper respiratory tract. Be-
cause of the difficulty in sampling the
LRT, most definitions of pneumonia
combine laboratory and clinical criteria.
However, by the time a child presents

Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.) S9

with sepsis, the details of respiratory ill-
ness may be difficult to elicit. Antibiotic
treatment may have already been initi-
ated before the onset of critical illness,
interfering with the ability to make a
microbiological diagnosis. Both viral and
bacterial pneumonia can cause life-
threatening LRT illness in any child. The
immunocompromised child is at higher
risk for severe fungal or parasitic pneu-
monia that requires admission to an ICU.
Microbiological confirmation is ulti-
mately obtained for about half of children
with community-acquired pneumonia
(7).
Pneumonia and bronchiolitis are the
two most common diagnoses in children
presenting to the ICU with respiratory
failure (8). Although bronchiolitis is
characterized by inflammatory obstruc-
tion of small airways, the initial clinical
presentation of tachypnea and wheeze
may progress to respiratory failure and be
difficult to distinguish from bacterial
pneumonia. Up to 50% of children hos-
pitalized for management of bronchiolitis
may have opacities on chest radiograph
(9). The chest radiograph in bronchiolitis
typically reveals hyperinflation and
patchy, shifting areas of diffuse infiltrate
and atelectasis. Wheezing infants with a
confirmed viral infection and atelectasis
that clearly shifts between chest radio-
graphs, however, should be classified as
having bronchiolitis and not pneumonia.
In addition to bronchiolitis, conges-
tive heart failure, acute respiratory dis-
tress syndrome, severe asthma, aspiration
pneumonitis, and in neonates, respira-
tory distress syndrome should be consid-
ered in the differential diagnosis of LRT
illness compatible with pneumonia. A
careful history, use of both radiologic and
microbiological tests, response to thera-
pies, and the evolution of the clinical and
radiologic picture usually allow the clini-
cian to differentiate these illnesses from
infectious pneumonia.
Children with nosocomial pneumonia
present further challenges. Underlying
LRT pathology, mechanical ventilation,
previous antibiotic exposure, and coloni-
zation by multiple-drug–resistant bacte-
ria and fungi all add to the complexities
of diagnosis and impair our ability to
assess the outcomes of our interventions.
Finally, complications of the infection
such as empyema or acute respiratory
distress syndrome associated with an
acute systemic inflammatory response
may alter the presentation of the respira-
tory tract illness.
S10
Components of a Definition of
Pneumonia
The components of the definition of
pneumonia that can be considered are
clinical signs and symptoms (e.g., cough,
retractions, wheezing and other signs of
respiratory distress, respiratory rate, fe-
ver, cyanosis, auscultatory findings), re-
sults of diagnostic imaging (e.g., chest
radiograph, computed tomographic
scan), and laboratory tests (microbiolog-
ical testing for specific pathogens
through serology or samples from the
respiratory tract, inflammation markers
such as white blood cell count, and dif-
ferential or acute inflammatory markers
such as C-reactive protein). In evaluating
each of these, it is useful to consider the
methodologic criteria used to evaluate
the accuracy of a diagnostic test. Some of
these criteria include independent, blind
comparison of the test in question with a
reference standard, inclusion in the eval-
uation of a spectrum of patients, and the
reproducibility, sensitivity, and specificity
of the test (10, 11)
Studies examining the sensitivity,
specificity, and likelihood ratios of vari-
ous respiratory signs in the diagnosis of
pneumonia in the nonventilated child
have been reviewed (4, 12). In most stud-
ies, the reference standard has been ra-
diographic evidence. No single finding
can confirm the diagnosis of pneumonia.
The absence of respiratory distress,
tachypnea, crackles, and decreased breath
sounds is up to 100% accurate in exclud-
ing community-acquired pneumonia
(13–16). The presence of crackles has a
likelihood ratio from 2 (13, 14, 17) to 15
(18) and is not present in up to 50% of
cases. Observation of chest retractions
also has variable performance. Cyanosis
is a specific sign for inadequate air ex-
change but occurs late, is uncommon,
and indicates severe hypoxia. Fever is a
nonspecific sign. The absence of fever has
a negative predictive value of up to 97%
for serious bacterial infection for children
⬍17 yrs old when temperature has not
been modified by antipyretics. Tachypnea
may be the best predictor of inadequate
air exchange and is used by the World
Health Organization in their algorithm
for triaging sick children (Integrated
Management of Childhood Illness) (19). A
normal respiratory rate does not exclude
pneumonia. In general, signs that are ob-
served have better reproducibility than
auscultatory findings. No studies were
identified that validated signs and symp-
Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.)
toms of pneumonia in the ventilated
child.
Almost every published definition uses
radiographic findings, “new or changing
infiltrate” as part of a pneumonia defini-
tion (3, 20 –24). Chest radiographs can-
not differentiate between bacterial and
viral causes and can be nonspecific (e.g.,
atelectasis, edema, hemorrhage).
A white blood cell count of ⬎15,000/
mm3 in young febrile children with no
focus of infection has a sensitivity of
ⵑ65% for pneumonia (25). Erythrocyte
sedimentation rate, C-reactive protein,
and other acute-phase reactants are non-
specific inflammatory markers that may
be useful in combination with other signs
of sepsis; however, no specific validation
studies in this setting were identified.
The most helpful laboratory tests for
the diagnosis of pneumonia are those
that identify a respiratory pathogen
rather than providing nonspecific evi-
dence of an inflammatory response. Ex-
pectorated sputum can usually not be
produced in children ⬍7 yrs old and is
likely to be contaminated with normal
oral and respiratory flora. Nasopharyn-
geal swabs in the presence of pharyngitis
for bacterial culture or rapid diagnosis
may identify group A streptococcal infec-
tion of the throat but would not be diag-
nostic of LRT infection due to this patho-
gen. Limited data on upper respiratory
tract (throat, nasopharynx) polymerase
chain reaction tests for respiratory vi-
ruses (respiratory syncytial virus, influ-
enza A and B, parainfluenza 1, 2, 3, ade-
novirus) and some bacteria have a
specificity and sensitivity of ⬎95% as per-
formed in some centers. Blood cultures
are not sensitive but are specific in asso-
ciation with radiographic evidence of
pneumonia. Serologic diagnosis gener-
ally requires two blood samples at least
10 days to 2 wks apart, but an elevated
immunoglobulin M antibody for some
pathogens may be reported in a timely
manner. The reader is referred to com-
prehensive reviews for guidance about
specific microbiological diagnosis of re-
spiratory pathogens (3).
Specimens from the LRT are most
likely to be obtained in the critically ill
child with respiratory failure who re-
quires mechanical ventilation. Several
methods to avoid contamination of spec-
imens by the upper respiratory tract have
been developed, including bronchoscopi-
cally obtained protected specimen brush
(PSB), bronchoscopic bronchoalveolar
lavage (BAL) and tracheal aspirate, and
nonbronchoscopic (i.e., “blind”) bron-
chial suction, blind mini-BAL, and
blind PSB. Ventilator-associated pneu-
monia is infection acquired after ⱖ48 hrs
of mechanical ventilation. The diagnostic
accuracy of various procedures used to es-
tablish a diagnosis of ventilator-associated
pneumonia has recently been reviewed for
adult patients (26, 27). The most sensitive
and specific procedures to diagnose venti-
lator-associated pneumonia are not as well
defined for neonates, infants, and children
(28, 29). Although protected specimen
brush samples and bronchoalveolar lavage
have been compared in adults and have
greater specificity (with greater risk) in
achieving a microbiological diagnosis, lim-
ited data exist for children. More recent
limited data are available for blind, nonbro-
nchoscopic bronchoalveolar lavage testing
in children (30). Particularly for ventilated
patients, a clinical impression of pneumo-
nia (29, 31) or radiologic changes alone are
poorly predictive of ventilator-associated
pneumonia (26, 32). Composite scores,
such as the Clinical Pulmonary Infection
Score (32), that combine clinical findings,
laboratory values, and chest radiographic
results, have been developed for use in
adult populations with ventilator-associ-
ated pneumonia. The development and val-
idation of composite scores in children will
be hampered by the lack of a gold or refer-
ence standard in most pediatric patients
against which to compare the predictive
score.
Proposed Definitions
Surveillance. The Centers for Disease
Control and Prevention developed defini-
tions for nosocomial infections several
decades ago for use in the National Nos-
ocomial Infections Surveillance System
(20), and these have been used by others
around the world to benchmark individ-
ual hospitals against published rates.
Data that include the target popula-
tions of critically ill newborns (neonatal
ICUs) and children (pediatric ICUs) are
reported regularly (33). We propose that
this definition continue to be used for the
surveillance of nosocomial pneumonia
using the denominator of 1000 ventilator
days for ventilated children and (33) pa-
tient days or number of discharges for
those who are not ventilated. To evaluate
these definitions in children, it would be
useful to systematically collect data for
which items in the diagnostic criteria are
contributing to the diagnosis.
The population-based incidence of
community-acquired pneumonia is not
an outcome tracked in most public sur-
veillance programs and, thus, is derived
from secondary data sources from hospi-
talizations, ambulatory care visits, or the
few community cohort studies. Should a
standard definition for surveillance of
community-acquired pneumonia be
needed, we propose that “probable” com-
munity-acquired pneumonia be defined as:
new onset of symptoms suggestive of LRT
illness (i.e., at least one of tachypnea, re-
tractions, cough, hypoxia) and fever
(⬎38°C) and a new radiographic opacity in
a child without preexisting pulmonary dis-
ease or two or more serial chest radio-
graphs with a new or progressive radio-
graphic opacity. Definite community-
acquired pneumonia would be defined as
that which meets criteria for probable com-
munity-acquired pneumonia and also has
microbiological confirmation (Table 4).
For Enrollment in Sepsis Trials, Diag-
nosis, and Therapy. Definitions for use in
research studies and for clinical care can be
more demanding than surveillance defini-
tions and may accordingly have more rig-
orous expectations for microbiological con-
firmation. The higher specificity of these
definitions, compared, for example, with
those for surveillance purposes, may come
at the cost of lower sensitivity. It is consid-
ered important to classify children cor-
rectly as having pneumonia when evaluat-
ing the efficacy of interventions for
critically ill children with pneumonia. Def-
initions for community-acquired and nos-
ocomial pneumonia, based on draft guide-
lines for industry from the U.S. Food and
Drug Administration (22, 23), are provided
in Tables 2 and 3. The diagnosis may be
considered definite if microbiologically
confirmed. The diagnosis is considered
probable in the case of a clinically compat-
ible illness with a positive Gram stain or
similar indirect evidence of a pathogen. The
diagnosis should be categorized as possible

Table 1. Centers for Disease Control and Prevention definitions of nosocomial pneumonia

1. Infants of ⱕ12 months of age

A. Without a chest radiograph must have at least two of the following signs or symptoms (apnea, tachypnea, bradycardia, wheezing, rhonchi, or
cough) AND any of the following (a–f)
a. increased production of respiratory secretions
b. new onset of purulent sputum or change in character of sputum
c. organism isolated from blood culture or diagnostic single-antibody titer (immunoglobulin [Ig]M) or four-fold increase in paired sera (IgG) for
pathogen
d. isolation of pathogen from specimen obtained by transtracheal aspirate, bronchial brushing, or biopsy
e. isolation of virus or detection of viral antigen in respiratory secretions
f. histopathologic evidence of pneumonia
B. With a chest radiograph must have a new or progressive infiltrate, cavitation, consolidation, or pleural effusion AND any of the features listed
above in A (a–f)
2. Children of ⬎12 months of age
A. Without a chest radiograph, the patient must have rales (crackles) or dullness to percussion on physical examination of the chest AND any of
the following (a–c)
a. new onset of purulent sputum or change in character of sputum
b. organism isolated from blood culture
c. isolation of pathogen from a lower respiratory tract specimen obtained by transtracheal aspirate, bronchial brushing, or biopsy
B. With a chest radiograph, the patient must have a new or progressive infiltrate, cavitation, consolidation, or pleural effusion AND any of the
following (a–g)
a. increased production of respiratory secretions
b. new onset of purulent sputum or change in character of sputum
c. organism isolated from blood or diagnostic single-antibody titer (IgM) or four-fold increase in paired serum samples (IgG) for pathogen
d. isolation of pathogen from specimen obtained by transtracheal aspirate, bronchial brushing, or biopsy
e. isolation of virus or detection of viral antigen in respiratory secretions
f. histopathologic evidence of pneumonia

Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.) S11

Table 2. Diagnosis of community-acquired pneumonia in the immunocompetent child

Community-acquired pneumonia is an acute, symptomatic infection of the pulmonary parenchyma in a child who has not been hospitalized in a
healthcare facility for ⱕ14 days before the onset of symptoms. The diagnosis requires two clinical findings, plus fever and tachypnea, and
laboratory and radiographic confirmation.
Clinical findings (at least two of the following)
Cough
New onset of lower respiratory tract secretions, change in character of secretions, or increase in the quantity of secretions or suctioning
requirements
Auscultatory findings of pneumonia or consolidation (rales, bronchial breath sounds, egophony, decreased breath sounds)
Dyspnea (or appearance of being “air hungry”)
Hypoxemia (PO2 ⬍60 mm Hg in room air)
Vital signs (fever, tachypnea)
Fever (defined by age group, for oral, rectal, and axillary): 3–24 mos old, ⱖ38.3°C; ⬎2 years of age, ⬎38°C
Tachypnea (defined by age group)
Laboratory
WBC ⬎15,000 and ⬎10% bands, or WBC ⬍4000
Radiographic
Within 48 hrs before institution of therapy, the chest radiograph should show the presence of a new infiltrate(s) consistent with infection
(interstitial, bronchial, alveolar), consolidation, cavitation, abscess or pneumatocele. The state of hydration of the patient at the time of the initial
radiograph should be taken into consideration. Repeat films after hydration or diuresis are acceptable, provided they are taken within 48 hrs.

WBC, white blood cell count.

Sensitivity and specificity vary by center, by investigator, by patient type, by duration of pneumonia, by pathogen, by underlying co-morbidities (eg,
immune compromise) and by instrument. These numbers should only be considered rough estimates for pediatrics.

Table 3. Definition of nosocomial pneumonia

Nosocomial pneumonia is defined as pneumonia developing after ⱖ3 days of hospitalization or occurring ⬍7 days after hospital discharge. Ventilator-
associated pneumonia is defined as occurring ⱖ48 hrs after initiation of mechanical ventilation. Radiographic evidence of pneumonia is
considered a new or progressive infiltrate consistent with infection (interstitial, bronchial, alveolar), consolidation, cavitation, abscess or
pneumatocele.
For a child of ⬍1 yr of age: radiographic evidence of pneumonia, plus worsening gas exchange (oxygenation desaturation episodes, increased oxygen
requirement, or increased ventilation requirement), PLUS at least three of the traits from the clinical and vital signs categories.
Clinical
Cough
Wheezing, rales, or rhonchi
Apnea, tachypnea, nasal flaring with retraction of chest wall or grunting
New onset of lower respiratory tract secretions, change in character of secretions, or increase in the quantity of secretions or suctioning
requirements
Vital signs
Temperature instability
Bradycardia or tachycardia appropriate for age
For a child between 1 and 12 yrs of age: radiographic evidence of pneumonia PLUS at least three criteria below from the clinical, vital signs, and
laboratory categories.
Clinical
Cough
Wheezing, rales, or rhonchi
Apnea, tachypnea, nasal flaring with retraction of chest wall, or grunting
Worsening gas exchange (oxygenation desaturation episodes, increased oxygen requirement, or increased ventilation requirement)
New onset of purulent sputum, or change in character of sputum, or increased respiratory secretions, or increased suctioning requirements
Vital signs
Temperature of ⬎38.4°C or hypothermia (⬍36.5°C) with no other recognized cause
Laboratory
Peripheral WBC ⬎15,000 with ⬎10% bands, or WBC ⬍4000

WBC, white blood cell count.

in the case of a clinically compatible illness
without culture or histologic confirmation.
Children should be evaluated at study entry
for clinical, laboratory, and radiographic
evidence of pneumonia, but confirmation
of the diagnosis may occur some time later.
Much remains to be learned about the
accuracy of clinical signs and symptoms,
laboratory tests, and imaging techniques
in the diagnosis of pneumonia in criti-
cally ill newborns, infants, and children.
The most accurate cutoffs for quantita-
tive measurement of microbiological
growth in LRT specimens obtained by
different sampling techniques should be
defined. The applicability of these general
definitions to subpopulations of children
(e.g., children with cystic fibrosis, chronic
aspiration, immunocompromise, prematu-
rity) should be evaluated so that benefits or
harms of interventions to these specific
groups are not missed. Definitions specific
to these subpopulations, in whom the nat-
ural history and outcome of pneumonia
may vary, may need to be developed.
The advent of molecular diagnoses of
infectious diseases and advances in inva-
sive techniques that sample the LRT
should allow validation of diagnostic in-
formation that is available to the clini-
cian. Accurate diagnostic criteria will al-
low us to design the most efficient
clinical trials and offer the most specific

S12 Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.)

Table 4. Criteria for the confirmation of a diagnosis of “definite” pneumonia
Criteria
Sputum from deep expectoration
Endotracheal aspiration
Bronchoscopy with BAL
Bronchoscopy with PSB
Blind PSB
Positive blood culture for a respiratory tract pathogen
Positive pleural fluid cultures
Isolation of virus or detection of viral antigen in
respiratory secretions
Diagnostic single-antibody titer (immunoglobulin M)
or four-fold increase in paired sera
(immunoglobulin G) for pathogen
Histopathologic evidence of pneumonia
Polymerase chain reaction or other genomic
identification of respiratory pathogen from lower
respiratory tract specimen
BAL, bronchoalveolar lavage; PSB, protected brush specimen.
therapies and interventions to the criti-
cally ill child.
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