Defining urinary tract infection in the critically ill child

Joanne M. Langley, MD

Objective: To define urinary tract infections in critically ill
children in the intensive care unit setting for the purpose of
surveillance of infection, enrollment of children in sepsis trials,
and for trials of therapy and prevention.
Design: Summary of the literature with review and consensus
by experts in the field.
Results: A variety of definitions, only some of which have been
validated for use in children, were identified. The Centers for Disease
Control criteria for the definition of nosocomial infection have been
used to establish surveillance data for inter-institutional comparison.
Validated definitions for the febrile child were identified. Using the
known characteristics of symptoms, signs, and laboratory criteria for
urinary tract infections, definitions for definite, possible, and proba-
ble urinary tract infection were derived.
Conclusions: Definitions for definite, probable, and possible
urinary tract infection were achieved by consensus that can be
used for surveillance and enrolment in sepsis trials. Future re-
search should determine the utility of these definitions in the
critically ill child and adapt them accordingly. (Pediatr Crit Care
Med 2005; 6[Suppl.]:S25–S29)
KEY WORDS: urinary tract infection; critically ill children; inten-
sive care unit; sepsis trials

U rinary tract infections (UTIs)
are common in childhood,
occurring in about 5% of fe-
brile infants and 2% of febrile
children of ⬍5 yrs of age (1, 2). In pedi-
atric intensive care units, nosocomial
UTIs comprise 13% of all nosocomial in-
fections, with a median incidence of 4.3
episodes per 1000 catheter days (3). Re-
view of the literature indicates that sec-
ondary bacteremia, or urosepsis, is un-
usual, except in young febrile infants and
catheterized critically ill children in
whom it occurs in up to 3% (Table 1).
Fungal infections of the urinary tract are
increasing in frequency (4), likely due to
use of invasive devices that impair phys-
ical host defenses and use of antimicro-
bial agents that eliminate commensal
flora. Fungal UTIs seem to be associated
with morbidity and mortality, particu-
larly in very-low-birthweight premature
infants (5).
In intensive care units, urinary tract
catheterization is the most important
From the Clinical Trials Research Centre, the IWK
Health Centre and Departments of Pediatrics, and
Community Health and Epidemiology, Dalhousie Uni-
versity, Halifax, Nova Scotia, Canada.
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.0000161934.79270.66
risk factor for UTI. The risk of infection
with a single catheterization in adults is
1–2% (6). In an open urinary drainage
system, bacteruria occurs in 1–2 days;
with a closed drainage system, one half of
patients will be bacteriuric within 10 days
to 2 wks; most will be bacteriuric by the
end of 30 days (7). In catheterized adult
intensive care unit patients, the isolation
of ⬎103 colony-forming units (cfu)/mL is
highly predictive of infection and will in-
crease to ⬎105 cfu/mL in the absence of
antibiotic therapy (8). In addition to the
morbidity associated with UTIs in the
critically ill child, it is important to prop-
erly identify and manage UTIs and uro-
sepsis in children to optimize antibiotic
use and reduce a reservoir of pathogens,
which may spread to others.
Considerations in the Diagnosis
and Definition of UTI in
Critically Ill Children
In attempting to define UTI, it is
worthwhile to consider some of the char-
acteristics of infection of the urinary tract
that assist or interfere with our ability to
distinguish true infection from coloniza-
tion or contamination. The term UTI is
used as a general term for a number of
clinical illnesses that could be localized
between the kidney to the urethra. Al-
though urine is normally sterile, the uri-
nary tract is contiguous with nonsterile
mucosal and cutaneous surfaces colo-
nized with commensal, nonpathogenic
flora. Bacteria that reach the urethra or
bladder are usually flushed out by voiding
and countered by other urinary tract de-
fense mechanisms. The method used to
collect a urine specimen can affect inter-
pretation of the culture results because
small numbers of bacteria may be found
normally in the distal tract, and periure-
thral area colonization can contaminate
the sample. For example, a commonly
accepted standard in microbiology labo-
ratories is to only report species and an-
timicrobial susceptibility results on urine
cultures with fewer than two or three
organisms in significant numbers. Urine
may be obtained from a “bagged” urine,
fresh voided midstream, in-out catheter-
ization, indwelling catheter, or a percu-
taneous suprapubic bladder-tap aspira-
tion. Because bagged urines may be
contaminated by skin flora, they are not
recommended for UTI diagnosis. Criti-
cally ill children are unlikely to be able to
provide voided midstream urine. In the
intensive care unit population, then,
most samples will be obtained by the
three latter methods. Indwelling cathe-
ters are likely to be colonized and may
yield falsely positive urinary tract cul-
tures.
Because bacteruria or funguria may
occur without causing illness, many pub-
lished UTI definitions combine laboratory
with clinical criteria. Critically ill infants
and children and their caregivers will of-
ten be unable to report specific signs or
symptoms referable to the urinary tract,

Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.) S25

Table 1. Frequency of nosocomial urinary tract infections in children in review of the literature

Incidence
Author Percentage Secondary
(Reference No.) Surveillance Period Setting Frequency of NUTI (n) of All NI Bacteremia

NNIS (3) June 1995 to June 2003 75 U.S. PICUs 4.3/1000 catheter days (median) NR NR
Matlow et al. (20) December 1997 to July 1999 PICU 0.95/100 admissions NR NR
Sohn et al. (21) Point prevalence, 1999 29 NICUs 1.2% (10/827) 10.6% NR
Grohskopf et al. (22) Point prevalence, 1999 31 PICUs 1.96% (10/511) 13% NR
Stover et al. (23) 1997 35 PICUs and 33 NICUs 5.4/1000 urinary catheter days NR NR
Langley et al. (24) 1991–1997 Pediatric hospital 0.39/100 discharges 10% 2.3% (no deaths)
0.7/1000 patient days (129)
Orrett et al. (25) 1992–1996 University hospital, 5.1/100 admissions (1,360) 42% 0
pediatric beds
Bell et al. (26) August 1986 to January 1990 Pediatric trauma center 1.5/100 admissions (7) 19.4% NR
Davies et al. (27) April 1989 to March 1991 Pediatric hospital 0.8 infections/100 admissions (351) 10.4% 2.9% (no deaths)
Weber et al. (28) January 1990 to December 1991 Pediatric burn facility 13.8/1000 catheter days (19) 17.9% NR
Lohr et al. (29) March 1988 to April 1990 Pediatric hospital 1.42/100 admissions (44) NR 0
Campins et al. (30) May 1990 (2 wks) 113 pediatric hospitals NR (52) 13.1% NR
Ford-Jones et al. (31) 1984–1987 Pediatric hospital 0.36/100 admissions (284) 6% NR
Lohr et al. (32) January 1981 to December 1985 Pediatric hospital 0.36/100 admissions (60) NR 0
Welliver and March 1980 to February 28, 1981 Pediatric hospital 0.36/100 discharges (62) 8.9% NR
McLaughlin (33)
Wenzel et al. (34) September 1972 to August 1975 University hospital, 2.1/100 admissions (74) 24.8% NR
pediatric beds

NUTI, neonatal urinary tract infection; NI, neonatal infection; NNIS, National Nosocomial Infections Surveillance; PICU, pediatric intensive care unit;
NR, not reported; NICU, neonatal intensive care unit.

such as frequency, dysuria, incontinence,
abdominal, suprapubic, or back pain.
Changes in urine color or smell may be
noted by caregivers but are not specific
for infection. Definitions of UTI in the
intensive care unit setting therefore must
rely heavily on laboratory criteria.
Finally, rapid microbiological diag-
nostic techniques for identification and
quantification of urinary pathogens are
not routine in clinical diagnostic labora-
tories, so definitive diagnosis of UTI gen-
erally takes ⱖ24 hrs.
Definition of UTI in Critically Ill
Infants and Children
Laboratory tools for the definition of
UTIs consist of tests to determine the
presence and quantity of pyuria, of bac-
terial nitrite, and culture of urine to de-
termine species and quantity of the in-
fecting organism or organisms. Urine
specimens should be collected in sterile,
leak-proof containers and transported to
the laboratory within 2 hrs, or refriger-
ated at 4°C for a maximum of 24 hrs,
before processing (9).
Pyuria is a manifestation of inflamma-
tion, but it is not specific to infection.
Neutropenic children or newborns may
not be able to manifest pyuria. The leu-
kocyte esterase test is 76%– 85% sensitive
in the detection of esterases that have
been released from disrupted leukocytes.
White blood cells may be visualized by
examining centrifuged or uncentrifuged
urine that is either stained or viewed with
a hemocytometer.
The number of urinary white blood
cells that is considered abnormal varies
in the literature. Cutoffs used in the lit-
erature include any pyuria, ⬎5 leuko-
cytes (wbc)/high-power field (hpf), ⱖ10
wbc/hpf in unstained urinary sediment,
ⱖ10 wbc/mm3, and ⱖ100/mm3 (10).
The urinary nitrite test detects ni-
trates that have been produced by reduc-
tion of dietary nitrates by urinary bacte-
ria. Most Gram-negative organisms and
some staphylococci are capable of reduc-
ing nitrates. Fungi and many Gram-
positive organisms do not reduce ni-
trates. Nitrates must be exposed to
nitrate-reducing organisms for ⱖ4 hrs
before reduction can take place.
Studies done in the 1950s in fresh-
voided urine specimens of adult women
first established the concept that a colony
count of a single species of bacteria at
ⱖ105/mL was correlated with UTIs (11).
Since that time, it has become clear that
clinically significant or symptomatic in-
fections may occur with smaller colony
counts.
The most systematic validation of bac-
terial quantity in the pediatric population
was done by Hoberman et al. (1), who
evaluated ⬎2,000 children presenting to
an emergency department. They found
that the combination of a single pathogen
with colony counts of ⱖ50,000 cfu/mL
and a urine leukocyte count of 10/mm3
(uncentrifuged urine examined with he-
mocytometer) from specimens of cathe-
terized urine were most characteristic of
infection. The majority (93%) of children
with a single organism had ⱖ50,000 cfu/
mL, and 84% had counts of ⱖ100,000
cfu/mL. A meta-analysis of the literature
published from 1966 to 2001 on urine
screening tests for determining the risk
of UTIs in children (10) identified 48 ar-
ticles that compared the index test with
urine culture. The authors created 30
groups of individual or combined tests
and evaluated these with different cutoffs.
They narrowed eligible combinations
down to nine groups of tests that were
included in the construction of nine cor-
responding bivariate receiver-operating
characteristic curves. Pyuria ⱖ10/hpf (or
␮L) and any bacteruria per high-power
field had the best diagnostic performance.
This work is perhaps most relevant to the
construction of definitions for UTI in the
critically ill child who is potentially eligible
for enrolment in sepsis trials before the
diagnosis of UTI is able to be confirmed. A
comprehensive technical report on UTI in
febrile infants and young children com-
pleted for the American Academy of Pedi-
atrics reviews the accuracy of individual

S26 Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.)

Table 2. Centers for Disease Control and Prevention definitions for nosocomial urinary tract infection (17, 18)

A. Symptomatic urinary tract infection must meet at least one of the following criteria:
1. Patient has at least one of the following signs or symptoms with no other recognized cause: fever (⬎38°C), urgency, frequency, dysuria, or
suprapubic tenderness and patient has a positive urine culture, that is, ⱖ105 microorganisms/cm3 or urine with no more than two species of
microorganisms.
2. Patient has at least two of the following signs or symptoms with no other recognized cause: fever (⬎38°C), urgency, frequency, dysuria, or
suprapubic tenderness and at least one of the following:
a. Dipstick test positive for leukocyte esterase or nitrate
b. Pyuria (urine specimen with ⱖ10 white blood cells/mL or ⱖ WBC/high-power field of unspun urine)
c. Organisms seen on Gram stain of unspun urine
d. Two urine cultures with repeated isolation of the same uropathogen (Gram-negative bacteria or S. saprophyticus with ⱖ102 colonies/mL urine
in nonvoided specimens
e. Urine culture with ⱖ105 colonies/mL urine of single uropathogen in patient being treated with appropriate antimicrobial therapy
f. Physician’s diagnosis
g. Physician institutes appropriate antimicrobial therapy
3. Patient ⱕ12 months of age has one of the following: fever (⬎38°C), hypothermia (⬍37°C), apnea, bradycardia, dysuria, lethargy, or vomiting and
urine culture of ⱖ105 colonies/mL urine with no more than two species of organisms
4. Patient ⱕ12 months of age has one of the following: fever (⬎38°C), hypothermia (⬍37°C), apnea, bradycardia, dysuria, lethargy, or vomiting and
any of the following:
a. Dipstick test positive for leukocyte esterase or nitrate
b. Pyuria
c. Organisms seen on Gram stain of unspun urine
d. Two urine cultures with repeated isolation of same uropathogen with ⬎102 organisms/mL urine in nonvoided specimens
e. Urine culture with ⱖ105 colonies/mL urine of a single uropathogen in patient being treated with appropriate antimicrobial therapy
f. Physician’s diagnosis
g. Physician institutes appropriate antimicrobial therapy.
B. Asymptomatic bacteruria must meet either of the following criteria:
1. An indwelling urinary catheter is present within 7 days before urine is cultured and patient has no fever (⬎38°C), urgency, frequency, dysuria, or
suprapubic tenderness and has urine culture of ⱖ105 organisms/mL urine with no more than two species of organisms
2. No indwelling urinary catheter is present within 7 days before the first of two urine cultures with ⱖ105 organisms/mL urine of the same
organism with no more than two species of organisms, and patient has no fever (⬎38°C), urgency, frequency, dysuria, or suprapubic tenderness.
C. Other infections of the urinary tract (kidney, ureter, urethra, bladder or tissues surround the retroperitoneal or perinephric spaces) must meet one
of the following criteria:
1. Organism isolated from culture of fluid (other than urine) or tissue from affected site
2. An abscess or other evidence of infection seen on direct examination, during surgery, or by histopathologic examination
3. Two of the following: fever (⬎38°C), localized pain, or tenderness at involved site and any of the following:
a. Purulent drainage from affected site
b. Organism isolated from blood culture
c. Radiographic evidence of infection
d. Physician’s diagnosis
e. Physician institutes appropriate antimicrobial therapy
4. Patient ⱕ12 months of age has one of the following: fever (⬎38°C), hypothermia (⬍37°C), apnea, bradycardia, dysuria, lethargy, or vomiting and
urine culture of ⱖ105 colonies/mL urine with no more than two species of organisms.

tests for UTIs (12). They note that if only
cultures yielding ⬎1000 cfu/mL are consid-
ered positive, catheterization cultures have
95% sensitivity and 99% specificity.
It is not clear that diagnostic criteria
for bacterial UTI are generalizable to sus-
pected fungal infections of the urinary
tract. As with identification of bacteria in
urine specimens, the growth of fungus
may be asymptomatic or indicate coloni-
zation of a device, contamination, or true
infection. In our literature review, no
studies validating diagnostic criteria for
fungal UTI in the critically ill child were
found. A definition for fungal UTI is pro-
posed based in part on a previously pub-
lished definition (13).
No literature validating definitions of
UTI in immunosuppressed patients, pa-
tients with genitourinary abnormalities,
or in infants and children with catheter-
associated funguria were identified.
Although validation of bacterial quanti-
fication in catheterized patients has
been done in adults (14), similar studies
were not found in children. Newer tests
of inflammation such as procalcitonin
(15) may be useful in diagnosis of UTI
and should be considered in future
research in the intensive care unit set-
ting.
Definitions for Surveillance
Purposes
Surveillance systems are designed to
monitor the health of populations by
identifying and responding to changes in
reporting trends of specific diseases in
at-risk populations. Because surveillance
is conducted in multiple sites and may
involve personnel who are not clinicians
who diagnose disease, there is an attempt
to balance system attributes such as sim-
plicity and timeliness of reporting with
accuracy of data capture using standard
definitions (16). The Centers for Disease
Control (CDC) definitions for the surveil-
lance of nosocomial infections were de-
signed to capture infections that occur as
a result of health care. They allow com-
parison of rates across hospitals (17–19)
and can be used to look at intra-institu-
tional change over time. The National
Nosocomial Infections System has pub-
lished rates for targeted nosocomial in-
fections in neonatal and pediatric inten-
sive care units for more than a decade (3).
The CDC definitions for nosocomial UTI
are seen in Table 2. That definition catego-
rizes infections into symptomatic UTI,
asymptomatic bacteruria, and other infec-
tions of the urinary tract (kidney, bladder,
urethra, or tissues surrounding the retro-
peritoneal or perinephric spaces). Two of
these categories have separate definitions

Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.) S27

for children according to whether the patient
is greater or less than 12 months of age.
When evaluated for application to the
critically ill child, it is clear that the CDC
definitions for symptomatic UTI will have
limited use in the intensive care setting
because most patients cannot report symp-
tomatology due to age or acuity of illness.
Use of the definitions for asymptomatic UTI
will lead to misclassification of some cases
of bacteruria or funguria as infection, as
will cases that qualify simply because of
physician diagnosis or institution of anti-
microbial therapy. The definition for
asymptomatic UTI will also miss clinically
significant infection with bacterial concen-
trations of ⬍105/mL if two culture results
cannot be obtained, as required by the CDC
definition for colony counts of 102/mL. Pe-
diatricians will also be hesitant to obtain
two urine specimens by urinary catheter-
ization or suprapubic aspiration because
these procedures may be associated with
the risk of trauma and infection.
Despite the aforementioned problems in
application of CDC definitions to critically
ill children, it was the consensus of the
International Sepsis Forum on Sepsis in
Children that the CDC definitions for nos-
ocomial infection should continue to be
used for surveillance purposes. These defi-
nitions have been used for almost two de-
cades, and there is a large body of baseline
data established through the National Nos-
ocomial Infections System. To advance
knowledge about the validity of these defi-
nitions in critically ill children and to de-
termine the contribution of individual
items in the diagnostic criteria to the diag-
nosis, however, it is recommended that
data collection tools capture components of
the criteria used (e.g., physician’s diagno-
sis) rather than just whether nosocomial
UTI occurred. In addition, the data should
be collected using the criteria of isolation of
a single pathogen with colony counts of
ⱖ50,000 cfu/mL and leukocyte count of
10/mm3 (uncentrifuged urine) (1) so that
the effect of this lower threshold on UTI
rates in the critically ill child can be com-
pared with existing definitions.
Special mention should be made of the
difficulty of diagnosing fungal UTI. In con-
trast to bacterial UTI, in which there is
general agreement that colony counts are
correlated with symptomatology and the
likelihood of UTI, there is not clear corre-
lation between quantification of fungal
growth in urine and UTI diagnosis. Fur-
ther, some laboratories do not quantify fun-
gal growth, and others do not speciate the
growth, reporting only the presence of
S28
Table 3. Proposed definitions for definite, probable, and possible urinary tract infection (UTI) in
critically ill children
Definite UTI
1. Symptomatic UTI
One of the following: fever (⬎38°C), urgency, frequency, dysuria, or pain (abdominal,
suprapubic, back) or sepsis not due infection at another site and one of:
a urine culture of ⱖ105 colonies/mL urine with no more than two species of organisms
or
a single pathogen with colony counts of ⱖ50,000 colony-forming units/mL obtained from a
catheterized specimen and a leucocyte count of 10/mm3 (uncentrifuged urine)
2. Asymptomatic UTI
An indwelling urinary catheter is present within 7 days before urine is cultured and patient
has no fever (⬎38°C), (for newborn apnea, bradycardia) urgency, frequency, dysuria, or
suprapubic tenderness and has a urine culture of ⱖ105 organisms/mL urine with no more than
two species of organisms
or
No indwelling urinary catheter is present within 7 days before the first of two urine cultures
with ⱖ105 organisms/mL urine of the same organism with no more than two species of
organisms, and patient has no fever (⬎38°C), urgency, frequency, dysuria, or suprapubic
tenderness (for newborn apnea, bradycardia).
Probable UTI
No indwelling catheter is present and patient has fever (⬎38°C) and pyuria ⱖ10/high-power field
and any bacteria per high-power field of unspun urine OR ⱖ104 organisms/mL in a non-voided
specimen
Possible UTI
Patient has one of fever (⬎38°C), urgency, frequency, dysuria, or pain (abdominal, suprapubic,
back), sepsis (International Sepsis Forum definition) and
Dipstick test positive for leukocyte esterase or nitrate
or
ⱖ10 white blood cells/mL or ⱖ10 white blood cells per high-power field of unspun urine
or
Organisms seen on Gram stain of unspun urine
Table 4. Definition of fungal urinary tract infection in the critically ill newborn or child
Possible
In a catheterized patient, one culture of ⬎105 colony-forming units (cfu)/mL obtained from an
indwelling catheter.
Probable
a. In a noncatheterized patient, growth of ⬎103 cfu/mL in a urine specimen obtained by
urethral catheterization.
b. In a catheterized patient, one culture of ⬎104 cfu/mL obtained from an indwelling catheter
Definite
a. In a noncatheterized patient, growth of ⬎103 cfu/mL in a urine specimen obtained from
suprapubic aspiration or ⬎104 cfu/mL in a specimen obtained by urethral catheterization.
b. In a catheterized patient, one culture of ⬎105 cfu/mL obtained from an indwelling catheter
and one culture of ⬎103 cfu/mL in a catheter specimen,
or
In a catheterized patient, two consecutive cultures of ⬎105 cfu/mL obtained from an indwelling
catheter and one of:
Pyuria or positive leucocyte esterase or growth of fungal species from a sterile site (e.g. blood, CSF,
lung, kidney) or radiographic evidence of invasive mycoses of the kidney (e.g. “fungal balls” in kidney).
yeast. In the absence of sufficient literature sensitive and allow criteria other than
to guide the application of cutoff points and culture because this result is not avail-
to increase the specificity of the definitions, able until about 24 hrs from the time of
we have included colony counts. This is an presentation. Children could be enrolled
important area for future research. when symptoms or laboratory criteria
suggest UTI (i.e., probable or possible)
Definitions for Identifying and then confirmed as UTI if the culture
Infection Early to Enroll results are positive. Urine specimens
Children in Sepsis Trials and must be obtained in an aseptic manner by
for Trials of Diagnosis and clean catch in cooperative patients, in-
Therapy out catheterization, or suprapubic aspira-
tion. Proposed definitions for definite,
A definition of UTI for the purpose of probable, and possible UTI in critically ill
enrolling a child in sepsis trials should be children are provided in Table 3. They
Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.)
should be modified as future research and
clinical experience validates the extent to
which they identify children with clini-
cally significant infection, whether bacte-
rial or fungal (Table 4), of the urinary
tract (20 –34).
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