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Rate, Risk Factors, and Outcomes of Nosocomial Primary Bloodstream
Infection in Pediatric Intensive Care Unit Patients
Jeya S. Yogaraj, MPH*; Alexis M. Elward, MD‡; and Victoria J. Fraser, MD*
ABSTRACT. Objective. The objective of this study ABBREVIATIONS. PICU, pediatric intensive care unit; NNIS, Na-
was to determine the rate, risk factors, and outcomes of tional Nosocomial Infections Surveillance; SLCH, St Louis Chil-
nosocomial primary bloodstream infection in pediatric dren’s Hospital; PRISM III, Pediatric Risk of Mortality; aOR, ad-
intensive care unit (PICU) patients. justed odds ratio; CI, confidence interval.
Design. Prospective cohort study.
Settings. This study was performed at St Louis Chil-
B
dren’s Hospital, a 235-bed academic tertiary care center loodstream infections represent a major cause
with a combined 22-bed medical and surgical PICU. of hospital-acquired infections in pediatric in-
Patients. Subjects for this study were patients admit- tensive care unit (PICU) patients.1,2 According
ted to the PICU between September 1, 1999, and May 31, to the 1999 National Nosocomial Infections Surveil-
2000. lance (NNIS) report,2 bloodstream infections (28%)
Interventions. None. are the most frequent nosocomial infection reported
Outcome Measures. Patients were monitored for the in PICUs, followed by ventilator-associated pneumo-
development of nosocomial bloodstream infections from
the day of PICU admission until 48 hours after PICU
nias (21%). PICUs have one of the highest central
discharge. venous catheter-associated bloodstream infection
Results. Of 911 patients, 526 (58%) were male and 674 rates—7.7 infections per 1000 central venous catheter
(74%) were white. Congenital heart disease (29%), lung days—with only burn units and neonatal intensive
disease (25%), and genetic syndrome (18%) were com- care units surpassing these rates of bloodstream in-
mon. There were 65 episodes of primary bloodstream fection.5 Coagulase-negative staphylococci (38%) are
infection in 57 patients; 5 were polymicrobial and 7 pa- the most common pathogen, although Gram-nega-
tients had multiple bloodstream infections. Coagulase- tive rods are isolated in 25% of PICU patients with
negative Staphylococcus was the leading cause of blood- bloodstream infections.2
stream infection (n ⴝ 28), followed by Enterobacter
cloacae (n ⴝ 8). The rate of bloodstream infection was
The majority of literature concerning bloodstream
13.8 per 1000 central venous catheter days. In multiple infection is generated from studies of critically ill
logistic regression analysis, patients with bloodstream adult patients. In adults, independent risk factors for
infection were more likely to have multiple central ve- developing bloodstream infections include pro-
nous catheters (adjusted odds ratio [aOR]: 5.7; 95% con- longed hospitalization, severity of illness at admis-
fidence interval [CI]: 2.9 –10.9), arterial catheters (aOR: sion, comorbidities, exposure to invasive procedures,
5.5; 95% CI: 1.8 –16.3), invasive procedures performed in inappropriate antimicrobial therapy, immunosup-
the PICU (aOR: 4.0; 95%CI: 2.0 –7.8), and be transported pressive therapy, use of steroids, parenteral nutri-
out of the PICU (aOR: 3.4; 95% CI: 1.8 – 6.7) to the radiol- tion, and histamine type-2 receptor blockers.1,7–11
ogy or operating room suites. Severity of illness as mea-
sured by admission Pediatric Risk of Mortality score,
Critically ill adult patients with bloodstream infec-
underlying illnesses, and medications were not associ- tions have a longer hospital length-of-stay, higher
ated with increased risk of nosocomial bloodstream in- treatment costs, and greater risks for mortality.3 In a
fection. cohort of critically ill adult surgical patients, the ex-
Conclusions This study identified a high rate of cess hospital length-of-stay resulting from blood-
bloodstream infection among St Louis Children’s Hospi- stream infection is 24 days.3 The mean attributable
tal PICU patients. Risk factors for bloodstream infection cost of bloodstream infection is $40 000 per survivor,
were related more to process of care than to severity of and the attributable mortality rate is 35%.3 Unfortu-
illness. Additional research is needed to develop inter- nately, the substantial amount of literature on the
ventions to reduce nosocomial bloodstream infections in
children. Pediatrics 2002;110:481– 485; pediatric intensive
epidemiology of nosocomial infections in adults can-
care unit, nosocomial, bloodstream infection. not be directly extrapolated to children because of
the significant differences between adults and chil-
dren which include age, underlying medical condi-
tions, process of care, and type and distribution of
From the Division of Infectious Diseases, Departments of *Internal Medi-
cine and ‡Pediatrics, Washington University School of Medicine, St Louis,
pathogens.2,4,5
Missouri. Most PICUs care for a heterogeneous population
Received for publication Dec 17, 2001; accepted Apr 3, 2002. of children of varying age, diagnosis, and underlying
Reprint requests to (V.J.F.) Infectious Diseases Division, Washington Uni- illness, ranging from infants with congenital anom-
versity School of Medicine, Campus Box 8051, 660 S Euclid Ave, St Louis,
MO 63110. E-mail: vfraser@im.wustl.edu
alies to adolescents with multiple traumas. Conse-
PEDIATRICS (ISSN 0031 4005). Copyright © 2002 by the American Acad- quently, even patients admitted to the same PICU
emy of Pediatrics. may differ substantially in their risk for nosocomial
Patients RESULTS
Since September 1999, there has been an ongoing prospective A total of 911 patients were admitted to the PICU
cohort study of nosocomial infections in the PICU. Participants for between September 1, 1999, and May 31, 2000. Pa-
this study were patients admitted to the PICU between September tient demographics are reported in Table 1. There
1, 1999, and May 31, 2000, excluding patients who were older than
18 years of age, died within 24 hours of admission, or were was a white predominance (74%). Slightly over half
neonatal intensive care unit patients on extracorporeal membrane of the patients were male (58%). Approximately half
oxygenation occupying PICU bed space. Approval was obtained of the patient population was under 3 years of age.
from the Washington University School of Medicine Institutional Congenital heart disease (29%), lung disease (25%),
Review Board; a waiver of informed consent was requested and
granted. and genetic syndrome (18%) were common. Less
than 5% of the patient population were admitted
Data Collection because of immunodeficiency, diabetes, renal dis-
All eligible study patients were monitored for the development ease, multiple trauma, or burn. Fifty percent of the
of nosocomial infections from the day of PICU admission until 48 patients had an arterial catheter, and 12% had mul-
hours after PICU discharge. Data on demographics, underlying tiple central venous catheters. Seventy percent were
medical conditions, surgeries and procedures performed, use of mechanically ventilated, and 30% had 1 or more
antibiotics, steroids, stomach acid suppressants and immunosup-
pressants, hospital length of stay, PICU length of stay, PICU transfusions during their stay in the PICU.
discharge disposition, central venous catheter days, and ventilator Fifty-seven children developed 65 episodes of pri-
days were collected from the medical records and daily flow mary bloodstream infections during their PICU stay.
sheets by 1 of the investigators (A.M.E.). The variable “procedures Five episodes of bloodstream infection were polymi-
performed in the PICU” was a composite variable, describing the crobial, and 7 patients had multiple bloodstream in-
location in which procedures such as intubation, arterial and
central venous catheter placement, mediastinal exploration, and fections. The rate of bloodstream infection in this
initiation of extracorporeal membrane oxygenation occurred. Ad- population was 13.8 per 1000 central venous catheter
mission severity of illness was calculated using the Pediatric Risk days. The most common causative microorganisms
of Mortality (PRISM III) score, which is a weighted score, esti- are reported in Table 2. Gram-positive bacteria were
mated using 17 physiologic parameters from the first 24 hours of
PICU admission.12 Information on potential risk factors was col- responsible for most of these infections (55%). Coag-
lected on both cases and noncases throughout the duration of ulase negative Staphylococcus (n ⫽ 28) was the lead-
PICU stay. Antibiotic-coated central venous catheters are not used ing cause of bloodstream infection, followed by En-
in this PICU. Patients with ⬎1 central venous catheter placed were terobacter cloacae (n ⫽ 8). Candida species were
defined as having “multiple central venous catheters.” “Transport
out of the PICU” was defined as the physical movement of the
responsible for all 5 episodes of fungemia. There
patient out of the intensive care unit to the radiology department, were insufficient numbers of cases caused by any 1
operating room, or cardiac catheterization laboratory; specific des- organism to determine relationships between organ-
tinations were not evaluated separately in the multivariate anal- ism type and patient characteristics.
ysis. There were no clusters of infection or outbreaks during the The mean time to bloodstream infection was 11.7
study period.
days, median 10 days (range: 2–33 days).
Definitions Univariate analysis of differences in characteristics
Centers for Disease Control and Prevention (CDC) definitions
of patients with and without bloodstream infections
were used to diagnose nosocomial primary bloodstream infec- is summarized in Table 1. Only factors occurring in
tions.13 Primary bloodstream infection cases were diagnosed with ⬎10% of patients are reported in this table. Age,
bacteria or fungi in their blood, which were not present or incu- gender, and ethnicity were not significantly different
bating before hospital admission and without evidence of other between patients with and without bloodstream in-
localized infections. Microorganisms causing bloodstream infec-
tion were isolated using routine blood cultures and their antibiotic fections. Severity of illness at admission (PRISM III
susceptibility profiles were obtained from laboratory reports. Co- score) was higher in patients with bloodstream in-
agulase-negative Staphylococcus species was reported as a cause of fections. A higher proportion of patients with blood-
TABLE 2. Causative Pathogens of Bloodstream Infections TABLE 3. Logistic Regression Analysis: Independent Risk
Factors for Bloodstream Infection
Microorganisms Bloodstream Infections
N ⫽ 65 (%) Risk Factors aOR P Value
(95% CI)
Gram-positive bacteria
Coagulase-negative Staphylococcus 28 (43.0) Multiple venous catheters 5.7 (2.9–10.9) .001
Staphylococcus aureus 3 (4.6) Arterial catheter 5.5 (1.8–16.3) .002
Enterococcus spp 3 (4.6) Procedures performed in PICU 4.0 (2.0–7.8) .001
Gram-negative bacteria Transport out of PICU 3.4 (1.8–6.7) .001
Enterobacter cloacae 8 (12.3)
Pseudomonas aeruginosa 6 (9.2) The Hosmer and Lemeshow test significance was 0.39, and the ⫺2
Klebsiella pneumoniae 4 (6.1) log likelihood was 279.4
Serratia marcescens 4 (6.1)
Escherichia coli 1 (1.5)
Acinetobacter spp 1 (1.5) of bloodstream infection, as there were fewer pa-
Fungus tients with femoral and nontunneled subclavian cen-
Candida spp 5 (7.6)
tral venous catheters, and often these sites were used
to place subsequent central venous catheters.
Logistic regression analysis was used to identify
stream infection received transplants, immunosup- independent risk factors for bloodstream infections
pressive agents, histamine type-2 receptor blockers, (Table 3). Patients who had multiple central venous
total parenteral nutrition, antimicrobial agents, and catheters (adjusted odds ratio [aOR]: 5.7; 95% confi-
steroids. Patients with underlying medical condi- dence interval [CI]: 2.9 –10.9) and arterial catheters
tions, invasive devices, and those who underwent (aOR: 5.5; 95% CI: 1.8 –16.3) were nearly 6 times more
surgeries had an increased risk for developing blood- likely to develop bloodstream infections than pa-
stream infections in the univariate analysis. tients who were not exposed to these factors. Patients
Most central venous catheters were placed in the who had invasive procedures performed in the PICU
internal jugular vein. It was not possible to assess the (aOR: 4.0; 95% CI: 2.0 –7.8) or those who were trans-
relationship between site of catheterization and risk ported out of the PICU (aOR: 3.4; 95% CI: 1.8 – 6.7)
ARTICLES 483
Downloaded from pediatrics.aappublications.org at Eccles Health Sciences Lib on November 30, 2014
were also at increased risk for acquiring bloodstream specific policies or procedures exist for the manage-
infections. Severity of illness at admission, underly- ment of arterial catheter stopcocks.
ing medical conditions, length of stay before infec- Patients who had procedures performed in the
tion, and medications used before infection were not PICU and those who were transported out of PICU
independent risk factors for bloodstream infection in to the radiology or operating room suites were also
the logistic regression analysis. at higher risk for bloodstream infection. Breach of
Univariate analysis of the outcomes of blood- sterile technique during procedures and patient
stream infection revealed that patients with blood- transport may predispose these patients to the risk of
stream infections had longer PICU (24.4 ⫾ 26.5 vs infections. Adhering to strict aseptic techniques, min-
4.1 ⫾ 11.5 days) and hospital (41.2 ⫾ 38.4 vs 13.0 ⫾ imizing the number of staff handling a patient, and
24.9 days) length of stay. The crude mortality rate increasing access to disinfectants and sterile gloves
associated with bloodstream infection was 19.2%. during procedures and patient transport may reduce
bloodstream infections.
There are a few limitations to this study. This
DISCUSSION study was performed at a single academic tertiary
We performed a prospective cohort study to de- care center, so results from this study may not di-
termine the rate, risk factors, and outcomes associ- rectly apply to other institutions with different pa-
ated with bloodstream infection in PICU patients. tient populations and medical practices. Because the
The incidence of bloodstream infection is 13.8/1000 data were obtained over the course of only 9 months
central venous catheter days, which is within the between September and May, seasonal variations in
75th to 90th percentile reported by NNIS.2 The dis- frequency of bloodstream infection and causative mi-
tribution of causative microorganisms for blood- croorganism could not be assessed. Severity of illness
stream is similar to what has been reported in the (PRISM III score) was calculated only at admission,
NNIS data.2 These infections are predominantly and this score probably does not reflect severity of
caused by Gram-positive organisms, mostly coagu- illness at the time of infection, especially as the me-
lase-negative Staphylococcus species. Enterobacter sp dian time to bloodstream infection was 10 days. The
was the most common Gram-negative species re- prospective cohort study design limited our ability to
ported in PICU patients with bloodstream infections. determine the attributable excess mortality and
In multivariate analysis, risk factors related to pro- length of stay resulting from bloodstream infection.
cess of care, specifically multiple central venous cath- A more appropriate study design to determine the
eters, arterial catheters, procedures performed in the attributable morbidity and mortality of bloodstream
PICU, and transport out of the PICU were associated infection is a nested case-control study matching pa-
with bloodstream infection. Underlying medical con- tients on severity of illness at the time of infection,
ditions, severity of illness at admission, and length of which is planned.
PICU or hospital stay were not associated with The risk factors identified in this study are differ-
bloodstream infection in logistic regression analysis. ent from those described for adults and are more
The presence of an arterial catheter or multiple related to the processes of care. This study identified
central venous catheters also increased the risk for several areas where implementation of preventive
developing bloodstream infections. Arterial catheters strategies could reduce a large proportion of noso-
are frequently used in the management of critically comial infections. Additional analysis is needed to
ill patients for continuous blood pressure monitor- estimate the attributable morbidity, mortality, and
ing, and to obtain blood gas measurements. Frequent economic impact of bloodstream infections in the
sampling through stopcocks may lead to increased PICU.
opportunity for introduction of microorganisms into
these catheters. Contamination of central venous
ACKNOWLEDGMENTS
catheters at the time of insertion or when accessing
This work was supported by grants from Zeneca through the
the catheter may lead to subsequent development of Pediatric Infectious Diseases Society (Dr Elward), and in part by
catheter-related infections.14 Measures to reduce Centers for Disease Control and Prevention cooperative agree-
catheter-related bloodstream infection that have ment UR8/CCU715087 (Dr Fraser).
proven effective in adults include adherence to max-
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ARTICLES 485
Downloaded from pediatrics.aappublications.org at Eccles Health Sciences Lib on November 30, 2014
Rate, Risk Factors, and Outcomes of Nosocomial Primary Bloodstream Infection
in Pediatric Intensive Care Unit Patients
Jeya S. Yogaraj, Alexis M. Elward and Victoria J. Fraser
Pediatrics 2002;110;481
DOI: 10.1542/peds.110.3.481
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