Download Time to Detection of Bacterial Cultures in Infants Aged 0 to 90 Days

RESEARCH ARTICLE
Time to Detection of Bacterial Cultures in
Infants Aged 0 to 90 Days
AUTHORS
Rianna C. Evans, MD, Bryan R. Fine, MD, MPH
abstract
Division of Pediatric Hospital Medicine, Department
of Pediatrics, Children’s Hospital of The King’s
Daughters and Eastern Virginia Medical School,
Norfolk, Virginia
OBJECTIVE: To determine the time to detection (TTD) of positive results on
blood, urine, and cerebrospinal fluid (CSF) cultures taken during the evaluation
for serious bacterial infection (SBI) in otherwise healthy infants aged 0 to 90
days.
KEY WORDS
bacterial culture, febrile infants, serious
bacterial infection
ABBREVIATIONS
CSF: cerebrospinal fluid
CONS: coagulase-negative Staphylococcus
ED: emergency department
SBI: serious bacterial infection
TTD: time to detection
UTI: urinary tract infection
www.hospitalpediatrics.org
doi:10.1542/hpeds.2012-0025
Address correspondence to Rianna C.
Evans, MD, Children’s Hospital of The King’s
Daughters, Division of Pediatric Hospital
Medicine, 601 Children’s Lane, Norfolk, VA
23507. E-mail: [email protected]
HOSPITAL PEDIATRICS (ISSN Numbers: Print,
2154 - 1663; Online, 2154 - 1671).
Copyright © 2013 by the American Academy of
Pediatrics
FINANCIAL DISCLOSURE: The authors have
indicated they have no financial relationships
relevant to this article to disclose.
METHODS: This study was a retrospective chart review of infants aged 0 to 90
days with positive blood, urine, or CSF cultures drawn during evaluation for SBI
in the emergency department or inpatient setting. The TTD of positive culture
results, reason for testing, and age of the infant were recorded.
RESULTS: A total of 283 charts were reviewed related to 307 positive culture
results. Of the 101 positive results on blood culture, 38% were true pathogens
with a mean TTD of 13.3 hours; 97% were identified in ≤36 hours. Blood cultures
with TTD ≥36 hours were 7.8 times more likely to be contaminants compared with
those with TTD <36 hours. Of 192 positive results on urine culture, 58% were
true pathogens with a mean TTD of 21 hours; 95% were identified in ≤36
hours. Fifty percent of 14 positive CSF culture results were true pathogens
with a mean TTD of 28.9 hours; 86% were identified in ≤36 hours. When data
for infants ≤28 days of age were analyzed separately, TTD followed the same
patterns for positive blood and urine culture results as seen in all infants aged 0
to 90 days.
CONCLUSIONS: In certain clinical situations, the inpatient observation period
for infants under evaluation for SBI may be decreased to 36 hours.
FUNDING: No external funding.
INTRODUCTION
The management of young infants with fever is evolving with the advent of
improved bacterial culture systems and various protocols that aid in predicting the
risk for serious bacterial infections (SBIs). Febrile infants (temperature ≥38.0°C)
are initially seen in an outpatient setting such as the emergency department (ED)
or physician’s office and may be either managed in an outpatient or inpatient setting while awaiting bacterial culture results.1
Infants with fever or concern for SBI who are admitted to the hospital often
receive empiric antibiotic coverage and are clinically monitored for 48 hours
while awaiting blood, urine, and cerebrospinal fluid (CSF) culture results. This
time period is based on multiple previous studies reporting that nearly all clinically significant organisms will show growth on bacterial culture media within 48
hours2–4; however, many of these studies were performed before the institution of
continuous blood culture–monitoring systems, potentially inflating the reported
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time to detection (TTD). Several more
recent studies have shown that the
TTD of the majority of pathogenic
organisms on blood cultures in children is <24 hours,5–8 but these studies
were performed on infants in the ICU,
nursery, or those >1 month of age,
potentially excluding a large proportion of infants with fever managed by
general pediatricians.
An automated blood culture–monitoring
system has been in place in our hospital system since 1991. Many infants
with fever have urine and CSF cultures drawn as well, which are read
manually once per day in our laboratory. There are limited published data
on the TTD of urine and CSF cultures
of febrile infants and no identifiable
study including the TTD of bacterial
cultures in otherwise healthy infants
aged 0 to 28 days. The current study
was undertaken to determine if bacterial cultures taken in young infants
would show growth of pathogenic
bacteria in <36 hours, with the goal
of potentially discharging otherwise
healthy infants earlier than the standard 48-hour observation period.
METHODS
Study Population and Design
This study was a retrospective chart
review of positive results on blood,
urine, and CSF cultures drawn in the
ED or inpatient setting during the
evaluation for SBI in previously healthy
infants aged 0 to 90 days. Culture data
were obtained by using the PathNet
Microbiology Database (North Kansas
City, MO) within the Cerner electronic
medical record system. Inclusion and
exclusion criteria are listed in Table
1. All blood, urine, and CSF cultures
drawn in the specified population were
identified, and charts from all infants
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TABLE 1 Inclusion and Exclusion Criteria
Inclusion Criteria
Exclusion Criteria
Age 0–90 d at time culture was drawn
Report of blood, urine, and CSF culture
present in microbiology database between
October 1, 2007, and February 28, 2011
Cultures drawn in ED or inpatient setting
Blood cultures taken from central line
Urine cultures obtained while Foley
catheter in place
CSF cultures taken from a ventricular shunt
Urine cultures taken after urologic
surgery (ie, ureterostomy)
Any bacterial cultures taken while in the
NICU, PICU, or transitional care unit
Significant underlying medical or surgical
conditions
Repeat bacterial cultures taken from the
same patient during the same
hospitalization
with positive culture results were
manually reviewed by the authors.
The time period for charts selected for
review was from October 2007 (earliest available data in the database)
through February 2011.
incubation and reading (BD, Franklin
Lakes, NJ). The bottles are scanned
every 10 minutes, and if flagged as
positive, the sample is removed from
the bottle and Gram stained. The
specimen is then plated and read daily
for further identification of the organism
and susceptibilities.
Cultures were deemed “true pathogens” if the patient was treated for that
particular infection as determined by
the attending physician. Cultures were
deemed “contaminant” if the patient
was not treated for infection with
that organism. Data gathered from
chart review included the cultured
organism, TTD (in hours), infant’s age
(in days) at the time the culture was
drawn, chief complaint on presentation, and true pathogen versus contaminant in culture specimen based
on clinical course.
The institutional review board at
Eastern Virginia Medical School reviewed and approved this study.
Laboratory Protocols
The standard procedure in our institution is to obtain a 3- to 5-mL blood
specimen for culture, with a minimum
of 1 mL. Specimens are inoculated into BACTEC Peds Plus/F culture vials and placed on the BACTEC
9000 Fluorescent Series instrument for
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The minimum fluid collection requirement for urine and CSF culture is 0.5 mL.
Urine and CSF samples are immediately
plated and placed in an incubator. They
are then removed and read manually
once daily for growth.
Statistical Analysis
The data were analyzed by using
SAS version 9.2 (SAS Institute, Cary,
NC) and SPSS version 19 (SPSS Inc,
Chicago, IL) software. The average
TTD for blood, urine, and CSF samples
were determined by using data from
all positive samples. To determine the
relationship between average TTD and
percent contaminant, linear regression
analysis was performed. To examine the
relationship between outcome (treatment or no treatment) and TTD (≥36
hours or <36 hours), Pearson χ2 tests
were performed. If significant (P < .05),
this analysis was followed by odds ratio
analysis to further quantify the relationship’s significance. Similarly, χ2 analyses
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were conducted to determine the relationship between TTD (≥36 hours or <36
hours) and age of patient (≥28 days or
<28 days).
RESULTS
A total of 283 charts were reviewed
related to 307 positive culture results.
The mean TTD of the isolated organisms for each culture type is outlined
in Table 2.
A total of 2092 blood cultures were
drawn in the selected population, of
which 115 were positive (5.5%); 14
positive culture results met exclusion
criteria. Of the remaining 101 positive blood culture results, 38 (38%)
were deemed to be true pathogens
with a mean TTD of 13.3 hours. The
63 (62%) blood cultures deemed contaminant specimens had a mean TTD
of 24.9 hours. Of the blood cultures
treated as true pathogens, 97% were
identified in ≤36 hours (Fig 1). Linear
regression demonstrated a significant
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If CONS were excluded, the R2 would
increase to 0.8328 (Fig 3). However, with
inclusion of all pathogens, a relationship
was still demonstrated, with those positive urine culture results with a mean
TTD ≥36 hours being 4.005 times more
likely to be treated as a contaminant
compared with samples with a mean
TTD <36 hours.
relationship between average TTD
and percent contaminant with an R2 of
0.7876 (Fig 2). Blood cultures with TTD
≥36 hours were 7.827 times more likely
to be treated as a contaminant compared with blood samples identified in
<36 hours (P = .028).
There was a total of 2283 urine cultures
drawn in the selected population; 232
had positive results (10.2%). Forty positive culture results met exclusion criteria. Of the remaining 192 positive results
on urine culture, 111 (58%) true pathogens had a mean TTD of 21 hours versus
26.7 hours for the 81 (42%) contaminant
urine cultures. Of the urine cultures
treated as true pathogens, 95% were
identified in ≤36 hours (Fig 1). Linear
regression demonstrated a weak correlation between mean TTD and percent
contaminant for positive urine samples,
mainly due to the inclusion of coagulasenegative Staphylococcus (CONS), which
is commonly considered a urine contaminant and has a relatively rapid TTD.
A total of 1159 CSF cultures were drawn
in the selected population, of which 14
had positive (1.2%) results, and no exclusions were necessary. Of the 14 positive
culture results, 7 (50%) were true pathogens with a mean TTD of 28.9 hours, and
7 (50%) were contaminant specimens
with a mean TTD of 57.7 hours. Of the
CSF cultures treated as true pathogens,
86% were identified in ≤36 hours (Fig 1).
Due to small sample size, linear regression could not be performed for CSF
cultures.
Analysis of data for infants aged ≤28
days was limited due to small sample
TABLE 2 Mean TTD in Hours of Isolated Species for All Subjects
Organism
Blood(n)
Urine(n)
CSF(n)
Pathogen
Contaminant
Pathogen
Contaminant
Pathogen
Contaminant
Total
α-Hemolytic streptococci
Bacillus sp
Candida albicans
Citrobacter sp
CONS
Clostridium subterminale
Escherichia coli
Enterobacter sp
13.3 (38)
0
0
0
16.1 (1)
27.2 (1)
0
15.8 (14)
12.3 (2)
24.9 (63)
20.8 (12)
12.3 (5)
0
0
28 (35)
0
10.6 (1)
0
21.3 (111)
0
0
0
22 (2)
0
0
20.4 (84)
27.5 (4)
26.7 (81)
31.8 (6)
0
44 (1)
0
18.5 (8)
0
18.7 (15)
21.5 (2)
28.9 (7)
24 (1)
0
0
0
0
0
19 (1)
0
57.7 (7)
0
0
0
0
52.3 (4)
119 (1)
0
0
Enterococcus sp
Streptococcus agalactiae
K pneumoniae
Lactobacillus sp
Methicillin-resistant Staphylococcus aureus
Methicillin-sensitive S aureus
Micrococcus sp
Mixed respiratory flora
Moraxella sp
Nutritionally variant Streptococcus
S pneumoniae
Streptococcus salivarius
12.3 (2)
7.5 (7)
12.2 (4)
0
0
17.4 (1)
0
0
0
0
12.3 (4)
11.1 (1)
14.2 (1)
0
0
0
0
0
59.8 (1)
11.9 (2)
90.4 (1)
16.6 (1)
0
10.7 (1)
31.6 (5)
23.3 (4)
21.4 (11)
0
0
0
0
0
0
0
0
0
29.7 (15)
28.3 (8)
0
44 (2)
35 (2)
31.9 (11)
0
0
0
0
0
0
65 (1)
25 (2)
0
0
0
0
0
0
0
0
22 (2)
0
36 (1)
0
0
0
0
40 (1)
0
0
0
0
0
0
Three contaminant specimens with growth of multiple bacteria were excluded from the table.
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FIGURE 1 TTD of true pathogen bacterial cultures.
size. Forty percent of true pathogens
in blood cultures occurred in infants
aged ≤28 days (n = 16), and all produced positive results in <36 hours.
Twenty-seven percent of true pathogens in urine cultures occurred in
children aged ≤28 days (n = 30) with
1 sample detected at >36 hours. There
were 2 true positive results in CSF
samples in infants ≤28 days of age,
both detected in <36 hours. When
looking at the relationship between
TTD (≥36 hours or <36 hours) and
age of patient (≥28 days or <28 days),
there were no significant relationships
found; all P values were >.05. This finding
demonstrates that age of the infant (in
days) likely has no relationship to TTD.
DISCUSSION
Multiple studies of infants <90 days of
age have shown that the incidence of
FIGURE 2 Mean TTD for blood cultures according to percent contaminants for predominant
organism types. aKlebsiella pneumoniae and S pneumoniae with similar data points. b“Other”
includes all other samples with numbers too small for individual data point inclusion.
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SBI is great enough to warrant evaluation for the source of fever or illness. Current recommendations for
the evaluation and management of
the febrile infant involve risk stratification based on the age of the infant
and findings on laboratory testing; it is
recommended that infants in high-risk
categories be monitored on empirical
antibiotics in the inpatient setting while
awaiting bacterial culture results.1
Previous studies have evaluated the
TTD of bacterial cultures in the newborn population, as well as in infants
aged 28 to 90 days2–8; however, there
are many infants evaluated for SBI who
do not fall into these categories, and
culture methods have changed since
these studies were published. These
data suggest that, in the appropriate
clinical and social circumstances, the
physician may discontinue antibiotic
therapy at 36 hours if bacterial cultures continue to have negative results
during evaluation for SBI in otherwise
healthy infants.
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In practice, the extent of the laboratory evaluation and choice to administer antibiotics varies, and children
are frequently managed based on
provider preference and clinical judgment of the degree of illness.9,10 With
existing variation in practice, many
otherwise healthy infants with fever
are admitted to the hospital based
on provider experience and practice,
not necessarily with strict adherence
to published guidelines. Although the
risk and consequences of SBI in young
infants cannot be overlooked, those infants who are admitted to the hospital
and who are determined to be low risk
have, at most, an SBI rate of 1% to 3%.11
When weighing the risk of SBI in young
infants with fever, the downsides of
hospitalization must be considered.
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of bacterial growth on culture in our
microbiology laboratory. As in many
laboratory systems, urine and CSF
cultures are read once daily, thereby
potentially lengthening the reported
TTD. If urine and CSF cultures were
read twice daily, there would likely be
a shorter reported TTD for pathogenic
bacteria.
FIGURE 3 Mean TTD for urine according to percent contaminants for predominant
organism types. CONS were excluded (see text). a“Other” includes all other samples with
numbers too small for individual data point inclusion.
Within the Children’s Hospital Association network, an ED evaluation and a 48-hour hospital stay
in an otherwise healthy infant with
fever generally incurred a charge of
approximately $8000 in 2010.12 An
inpatient admission also exposes the
infant to iatrogenic complications
such as health care–associated infections, intravenous infiltration, and
antibiotic adverse effects as well as
causing significant parental emotional
and financial stress. Two studies have
described the iatrogenic complication
rate involved with the hospitalization
of the young febrile infant to be 20%
to 30%.13,14 These studies describe
complications including intravenous
infiltrations, diarrhea or bone marrow suppression attributed to antibiotic use, acquired infection, and drug
errors. Although the majority of these
complications were self-resolving
or easily treated, any complication
is difficult to face from the child’s or
parent’s perspective and may be less
likely to occur with shorter length of
hospitalization.
Notable to the current study was the
determination of true positive and
contaminant culture results based on
attending physician decision for treatment course. This methodology was
chosen due to subtle clinical and social
circumstances that are present with
each case which cannot reliably be
determined in chart review. We have
therefore included in the true positive
analysis 3 samples with positive blood
culture results with species generally
considered contaminants. A limitation to evaluating the TTD of bacterial
specimens is the method of detection
There were 5% of true positive urine
cultures detected in >36 hours; the
details of each case are outlined in
Table 3 and demonstrate increased
level of suspicion for UTI, treatment
before culture, or physician discretion for treatment. In addition, 2
pathogenic specimens in CSF were
detected at ≥36 hours, which require
discussion. The first case was an illappearing infant with a blood culture result at 11 hours positive for
Streptococcus pneumoniae in which
the CSF demonstrated growth of
the same organism at 36 hours; this
specimen was read initially at 4 hours
and not read again until the 36-hour
mark due to our laboratory’s process
of once-daily reading of cultures.
The second was an 8-day-old infant
of a 35-week twin gestation without
prenatal care presenting with hypothermia. This infant’s CSF culture
had detection of Enterococcus faecium at 65 hours; despite the lack of
TABLE 3 Case Details for Positive Urine Culture Results With TTD >36 Hours
Age, d
TTD, h
Organism
Case Details
44
75
60
55
47
75
10
48
41
38
E faecalis >100 000 CFU
Enterobacter amnigenus
>100 000 CFU
E faecalis 40 000 CFU
K pneumoniae 10 000 CFU
E coli 1000 CFU
81
37
E coli 1000 CFU
UA negative; history of previous UTI
UA negative but not performed until 24 h after
culture taken
UA with 0–2 WBC, few bacteria
UA with 0–2 WBC
10–25 WBC, many bacteria, large LE, and
positive nitrate; first urine culture at another
facility and this sample after antibiotic given
UA with 0 WBC, moderate LE; on antibiotic at
time of culture
CFU, colony-forming unit; LE, leukocyte esterase ; UA, urinalysis; WBC, white blood cell count.
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CSF pleocytosis and long TTD of the
organism, this infant was treated due
to ongoing hypothermia and apnea
with bradycardia. This study is limited
in the small number of CSF samples
available for analysis in the selected
population. Of 1159 CSF cultures performed in the population there were
7 positive samples treated as true
pathogens (0.6%). Our study found
that 86% of true pathogens in CSF
culture were identified in ≤36 hours;
therefore, we suggest using these
data to support discharge before
48 hours in a well-appearing infant
without significant CSF pleocytosis.
Future collaborative studies would be
helpful to gather more data regarding
the TTD of pathogenic bacteria in the
CSF of infants being evaluated for SBI.
We also suggest that physicians
become familiar with the methods
used for bacterial culture sampling
and monitoring in their institutions.
Due to the nature of this retrospective chart review, we were unable to
determine several factors that should
be taken into consideration in determining likelihood of bacterial growth
in culture; these include the bacterial
burden in the infant, amount of culture
fluid obtained, and previous administration of antibiotics. In addition, when
considering discharge of an infant
hospitalized during the evaluation for
SBI, the infant’s medical history and
social circumstances should be investigated and close follow-up arranged.
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CONCLUSIONS
a pediatric emergency department: current
In the wake of improved vaccination
for several serious bacterial pathogens
in young infants and improved bacterial culture technique, the evaluation
and management of SBIs are evolving.
Our study demonstrates that pathogenic bacteria are frequently identified in <36 hours. These data suggest
that, in the right clinical and social
circumstances, the physician may discontinue antibiotic therapy if bacterial
culture results remain negative at 36
hours in infants admitted to the hospital with fever. Future research in the
area of the TTD of CSF cultures would
strengthen this conclusion.
prevalence, time to detection, and outcome.
Pediatrics. 2000;106(3):505–511.
6. McGowan KL, Foster JA, Coffin SE. Outpatient pediatric blood cultures: time to positivity. Pediatrics. 2000;106(2 pt 1):251–255.
7. Kaplan RL, Harper MB, Baskin MN, Macone
AB, Mandl KD. Time to detection of positive
cultures in 28- to 90-day-old febrile infants.
Pediatrics. 2000;106(6). Available at: www.
pediatrics.org/cgi/content/full/106/6/e74.
8. Garcia-Prats JA, Cooper TR, Schneider VF,
Stager CE, Hansen TN. Rapid detection
of microorganisms in blood cultures of
newborn infants utilizing an automated
blood culture system. Pediatrics. 2000;105(3
pt 1):523–527.
9. Pantell RH, Newman TB, Bernzweig J, et al.
Management and outcomes of care of fever
in early infancy. JAMA. 2004;291(10):1203–
ACKNOWLEDGMENT
We thank Erin McGuire Kren, MS, and
Amy Perkins, MS, for their help with
statistical analyses.
1212.
10. Meehan WP 3rd, Fleegler E, Bachur RG.
Adherence to guidelines for managing the
well-appearing febrile infant: assessment
using a case-based, interactive survey.
Pediatr Emerg Care. 2010;26(12):875–880.
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