 |
|
Risk of Serious Bacterial Infection in Children With Fever Without a Source in the Post–Haemophilus influenzae Era When Antibiotics Are Reserved for Culture-Proven Bacteremia
Subhankar Bandyopadhyay, MD;
Jo Bergholte, MS;
Charles D. Blackwell, MD;
Jason R. Friedlander, MD;
Halim Hennes, MD, MS
Arch Pediatr Adolesc Med. 2002;156:512-517.
ABSTRACT
| |
Objective To determine the rate of serious bacterial infection in children aged
2 to 36 months with fever without a source in the post–Haemophilus influenzae era, when antibiotic therapy is reserved until
blood culture results turn positive.
Design and Setting Retrospective review of emergency department, urgent care center, and
hospital medical records from an urban children's hospital.
Participants Eligible participants were identified from hospital medical record and
microbiology laboratory databases. Immunocompetent individuals aged 2 to 36
months with fever without a source were eligible for enrollment. Exclusion
criteria were temperature less than 39.0°C, identifiable focus of infection,
current or recent antibiotic use, and hospital admission.
Interventions and Outcome Measures Enrolled participants were assigned to group 1 (blood culture obtained)
or group 2 (no blood culture) and did not receive empiric antibiotic treatment
in the emergency department, in the urgent care center, or for home use. Demographic
and outcome data were collected on all enrolled patients.
Results During the study, 9241 febrile children were identified; 2641 (29%)
met the enrollment criteria. Blood cultures (group 1) were performed on 1202
patients (46%), and 37 (3%) had culture-proven occult bacteremia (95% confidence
interval, 2.2%-4.2%). Streptococcus pneumoniae was
the most prevalent organism (84%). The mean ± SD time for reporting
a positive blood culture finding was 17.5 ± 8.5 hours. Two patients
(0.08%; 95% confidence interval, 0.009%-0.27%) developed serious bacterial
infection, and both recovered completely.
Conclusion Reserving antibiotic therapy for culture-proven occult bacteremia was
not associated with increased risk of developing serious bacterial infection
compared with previously published data.
INTRODUCTION
FEVER IS A COMMON pediatric complaint and accounts for approximately
20% of all pediatric emergency department (ED) visits.1
Children aged 2 to 36 months with fever without a source (FWS) are at risk
of developing occult bacteremia (OB) and may subsequently develop serious
bacterial infection (SBI).2-6
The evaluation and treatment of these children remains a challenge to physicians.
Previous recommendations suggest empiric treatment to prevent SBI in children
at risk for OB.7-8 Bacterial meningitis,
sepsis, and death are the outcomes that frequently drive empiric antibiotic
treatment in children with suspected OB. However, based on the results of
earlier studies,9-12
these outcomes are rare events, with an overall combined rate of 0.1% for
bacterial meningitis and sepsis in children with FWS. Since the introduction
in 1993 of practice guidelines by Baraff et al,7-8
widespread Haemophilus influenzae type b immunizations
and continuous blood culture monitoring systems have been implemented.13 Although recent meta-analyses14-15
have demonstrated a trend toward reduced risk of SBI with empiric antibiotic
treatment, statistical significance was not reached despite the large sample
sizes. Therefore, the utility of empiric antibiotic treatment may be less
than previously believed.
The objective of our study is to determine the rate of SBI in children
aged 2 to 36 months with FWS in the post–H influenzae era, when antibiotic therapy is reserved for culture-proven bacteremia.
PATIENTS AND METHODS
STUDY DESIGN AND SETTING
A retrospective review was performed of the medical records of febrile
patients aged 2 to 36 months who were evaluated in the ED or urgent care center
(UCC) of Children's Hospital of Wisconsin, an urban tertiary care children's
hospital. The study was approved by the institutional human rights review
board of Children's Hospital of Wisconsin.
STUDY POPULATION
Patients aged 2 to 36 months, evaluated between January 1, 1995, and
July 31, 2000, in the ED or UCC with fever (International
Classification of Diseases, Ninth Revision, code 780.6) as one of the
discharge diagnoses were identified from the hospital medical record database.
Our usual coding practice is to assign a fever code along with other diagnoses
where applicable if the patient presented with a complaint of fever. Thus,
we could identify most patients eligible to have blood samples taken because
of FWS in the ED and UCC from the hospital database alone. The eligibility
of patients' enrollment in the study was determined by reviewing the entire
ED and UCC visit records identified from the hospital medical record database
by the investigators. To ensure the enrollment of all patients from whom a
blood sample was drawn in the ED or UCC, we also reviewed the hospital microbiology
laboratory database. Immunocompetent children with a documented ED or UCC
rectal temperature of 39.0°C or greater were eligible for enrollment.
Exclusion criteria included (1) ED or UCC temperature less than 39.0°C;
(2) identifiable source of infection (otitis media, sinusitis, pneumonia,
urinary tract infection, meningitis, osteomyelitis, septic arthritis, cellulitis,
bronchiolitis, croup, gingivostomatitis, varicella, roseola, and fifth disease);
(3) current or recent use of antibiotics within 1 week preceding the ED or
UCC visit, antibiotic therapy in the ED or UCC, or prescription for use at
home; and (4) hospital admission. Patients with viral upper respiratory tract
infections and gastroenteritis were not excluded from our study.
STUDY PROTOCOL AND OUTCOME MEASUREMENTS
During the study, an ED clinical practice guideline for patients aged
2 to 24 months with FWS was in place that recommended obtaining a catheterized
urine specimen for urinalysis and culture in boys up to 6 to 12 months of
age and girls up to 12 to 24 months of age with a temperature of 39.0°C
or greater. Chest radiography was recommended only for patients with respiratory
tract symptoms, and complete blood cell count was not a routine test. Recommendation
for blood culture included all patients with a temperature of 41.0°C or
greater and, at the physician's discretion, for patients with a temperature
of 39.0°C to 40.9°C. Use of antibiotics was recommended only for patients
with an apparent bacterial focus of infection, suspected SBI requiring hospital
admission, or culture-proven bacteremia. Antibiotics were not recommended
for patients with FWS alone. Patients who were discharged from the hospital
received a printed comprehensive home care teaching sheet for febrile children
and were advised to return to the ED if they continued to have a temperature
of 39.0°C or greater, developed other symptoms, or appeared ill. A designated
callback nurse provided telephone follow-up within 24 to 48 hours of an ED
visit. Routine follow-up advice included continuation of antipyretic therapy
if the patient was still febrile or return to the ED if he or she appeared
irritable, lethargic, or had decreased intake/output or difficulty breathing.
Enrolled patients were classified according to Figure 1. Patients with an ED temperature of 39.0°C or greater
were assigned to either group 1 (blood culture obtained) or group 2 (no blood
culture). Blood cultures were performed using sterile techniques and were
inoculated into pediatric blood culture bottles (Bactec Peds Plus; Becton,
Dickinson and Co, Franklin Lakes, NJ). A single bottle containing an enriched
soybean-casein digest broth was inoculated with 0.5 to 1.0 mL of blood. Blood
culture bottles were immediately taken to the laboratory and loaded into a
continuous blood culture monitoring system, Bactec 9240 (Becton, Dickinson
and Co), which monitored the production of carbon dioxide every 10 minutes
through a fluorescent sensor. Bottles identified as positive were immediately
removed from the instrument for gram staining and were subcultured for bacterial
identification. The ED was notified immediately of all positive culture findings
and of the gram stain results by the laboratory technicians who are on duty
24 hours a day. A designated callback nurse on each shift was responsible
for informing the ED attending physician of and contacting the families or
the primary physician with positive blood culture results. The standard follow-up
advice for a patient with positive blood culture results was a return ED visit.
However, some primary care physicians elected a follow-up visit in their offices
instead.
|
|
|
|
Classification of study participants. T indicates temperature; FWS,
fever without a source; ED/UCC, emergency department or urgent care center;
and Cx, culture.
|
|
|
Demographic characteristics, associated symptoms, duration and height
of fever at home, ED or UCC temperature, blood culture results, disposition,
ED or UCC revisits, final diagnosis, and the development of SBI were abstracted
from the medical records. Additional data for patients with positive blood
culture results included time to positive culture findings, date and time
of follow-up visit, discharge diagnosis, disposition, and results of repeated
blood culture. Serious bacterial infection was defined as meningitis, septic
shock, or death due to an infectious cause within 2 weeks of the initial ED
visit. Children's Hospital of Wisconsin accounts for 93% of all pediatric
hospital admissions, including all critical care admissions, in the region
(Children's Hospital of Wisconsin, unpublished institutional data, 2000).
One of the faculty is a member of the county death review board, so it is
unlikely that a case of SBI as defined would be missed.
Bacteria that were considered pathogenic included Streptococcus pneumoniae, Staphylococcus aureus, group A streptococci, Enterococcus species, Neisseria meningitides,
Salmonella species, Moraxella catarrhalis, Pseudomonas species, H influenzae, Campylobacter organisms,
and Escherichia coli. Bacteria that were considered
contaminants were coagulase-negative Staphylococcus
species,  -hemolytic streptococci, nonpathogenic streptococcus, micrococcus, Clostridium species, Corynebacterium species, other gram-positive rods, and nonpathogenic Neisseria species. Time to positive culture results was measured in
hours.
STATISTICAL ANALYSIS
Continuous variables were compared using the unpaired, 2-tailed t test, and categorical data were compared using the  2 test. The Fisher exact test was used to evaluate small sample size
data. The 95% confidence interval (CI) was calculated when appropriate. The 
statistic was calculated on a random sample of 100 medical records to determine
the agreement rate on inclusion and exclusion criteria between the investigators.
All analyses were performed using statistical software (SPSS v10.05; SPSS
Inc, Chicago, Ill).
RESULTS
During the study, 9241 febrile patients were identified: 2641 (29%)
met the enrollment criteria and 6600 (71%) were excluded (Figure 1). Reasons for exclusion were identifiable focus of infection
(58%), ED or UCC temperature of less than 39.0°C (30%), antibiotic administration
in the ED or UCC or prescription for use at home or within 1 week preceding
the ED or UCC visit (9%), and hospital admission at the time of the initial
ED or UCC visit (3%). The demographic characteristics of enrolled patients
are summarized in Table 1. Blood
cultures (group 1) were obtained more frequently in younger children with
higher mean temperatures and a longer mean duration of fever. Also, a larger
proportion of patients in group 1 underwent urinalysis/culture and chest radiography
(Table 1).
|
|
|
|
Table 1. Demographic Characteristics of 2641 Patients With a Temperature
of 39.0°C or Greater*
|
|
|
Thirty-seven patients (3%) in group 1 (n = 1202) had culture-proven
OB (95% CI, 2.2%-4.2%). A higher rate of OB was observed in patients aged
13 to 24 months (4.0%) compared with those aged 2 to 6 months (1.8%). Most
pathogens (84%) were S pneumoniae (Table 2). Of the 37 patients with OB, 30 (81%) returned to the ED
after notification from our callback nurse, and 28 of these (93%) had another
blood culture performed. Seven (25%) of these 28 patients had persistent S pneumoniae bacteremia on the repeated blood culture.
Sixteen patients with OB (53%) were febrile at the time of the follow-up visit
and did not have an identifiable focus of bacterial infection. Seven patients
with OB had follow-up by their primary physician. No further microbiology
laboratory data were available for these patients, and no adverse outcome
or hospital admissions were documented on medical record review.
|
|
|
|
Table 2. Distribution of Pathogens in 37 Patients With Culture-Proven
Occult Bacteremia
|
|
|
Thirty-nine patients (3.2%; 95% CI, 2.3%-4.4%) had a contaminated blood
culture; 32 (82%) were coagulase-negative staphylococcus, 5 (13%) were -hemolytic
streptococcus, and 2 (5%) were micrococcus or other gram-positive rods. Twenty-two
patients (56%) returned to the ED on notification; 17 of them (77%) had another
blood culture performed and all were negative.
The hospital admission rate for patients with OB was 32% (n = 12) and
for those with contaminated blood culture it was 26% (n = 10). Reasons for
hospital admission included toxic or ill appearance, dehydration with persistent
vomiting or diarrhea, or respiratory tract symptoms requiring continuous monitoring.
The mean ± SD time to positive culture results for pathogenic
bacteria was 17.5 ± 8.4 hours and for contaminated blood culture was
40.4 ± 37.4 hours (mean difference, 23.0 hours; 95% CI, 8.0-37.2 hours).
The median time from report of positive blood culture result by the microbiology
laboratory to ED follow-up was 3.1 hours (range, 1.0-8.0 hours).
Two patients (0.08%; 95% CI, 0.009%-0.27%) developed SBI in our study
population (n = 2641). A 23-month-old boy with gram-negative diplococci in
blood samples had follow-up with his primary physician and was given oral
antibiotic treatment. He received a dose of intramuscular ceftriaxone sodium
on day 2 at the same physician's office for persistent fever and returned
to the ED on day 3 in septic shock. His initial blood culture in the ED was
positive for N meningitides, and his subsequent blood
and cerebrospinal fluid culture results were negative. The second patient
was a 2-month-old girl who had a blood culture positive for S pneumoniae. On her return visit to the ED she was febrile and appeared
ill. A complete sepsis evaluation was performed, she had cerebrospinal fluid
pleocytosis, and both her cerebrospinal fluid and repeated blood cultures
were positive for S pneumoniae. Both patients recovered
completely.
Seventy-seven patients (5%) from group 2 (n = 1439) who did not have
a blood culture performed during the initial visit returned to the ED or UCC
within 1 to 2 days for persistent fever. There was no identifiable focus of
bacterial infection noted in any of these patients. Twenty-six (34%) of these
patients had blood cultures performed at the second visit and all had negative
results. The statistic for agreement on inclusion and exclusion criteria
was 0.9.
COMMENT
In 1993, Baraff et al7-8
published practice guidelines recommending empiric antibiotic treatment for
children at risk for OB. However, there have been no prospective studies to
validate these recommendations, and the treatment of these children remains
controversial.16 In 4 previously published
prospective randomized clinical trials9-12
undertaken before the widespread use of H influenzae
type b vaccines (Table 3), the
combined rate of meningitis and sepsis in children treated with empiric antibiotics
was 0.08% (95% CI, 0.03%-0.17%). The overall rate of SBI in those 4 studies
is calculated according to our study definition of SBI being bacterial meningitis,
sepsis, or death due to an infectious cause. It is computed among patients
who received either parenteral or oral antibiotics during their initial visit
and pending blood culture results. Therefore, the reported rate of SBI was
0.08% (95% CI, 0.03%-0.17%; 6/7485).9-12
Although the total number of patients who developed SBI was 8, 2 were from
the no treatment group.12
|
|
|
|
Table 3. Historical Data: Prospective Randomized Clinical Trials of
Antibiotic Therapy for Children With Fever Without a Source*
|
|
|
In a meta-analysis, Bulloch and colleagues14
reported that the use of either oral antibiotics or intramuscular ceftriaxone
did trend toward a reduced risk of serious infection; however, neither reached
statistical significance (odds ratio [OR], 0.60; 95% CI, 0.10-3.49; and OR,
0.38; 95% CI, 0.12-1.17, respectively). The authors concluded that 414 patients
should receive empiric antibiotic therapy to prevent 1 SBI. In a similar meta-analysis,
the rate of SBI was compared in individuals with S pneumoniae bacteremia who received parenteral vs oral empiric antibiotic treatment.
There was no difference in the rate of SBI between the 2 groups (OR, 1.48;
95% CI, 0.5-4.3).15 In our study, the SBI rate,
based on 2 of 2641 patients, is 0.08% (95% CI, 0.009%-0.27%) and is comparable
with previously published data.9-12
The Centers for Disease Control and Prevention and American Academy of Pediatrics
recommendations17-18 for judicious
use of antibiotics were followed in our study, with a comparable outcome to
that reported in the previously mentioned trials. Even assuming that empiric
treatment would be 100% effective in preventing SBI compared with our expectant
approach, our findings suggest the need to treat 1250 patients to prevent
an additional case of SBI.
In contrast to previous studies on OB, we excluded children with otitis
media, which may have affected the rate of OB in our study.3, 9-13,19
However, the risk of OB in children with otitis media does not necessarily
increase their risk of developing SBI as defined in our study.20
Furthermore, oral antibiotics prescribed to treat otitis media may be effective
in treating bacteremia as well.4 Because our
objective was to determine the rate of SBI in children with FWS when antibiotic
therapy is reserved until blood culture results are positive, we excluded
this group of patients from our analysis.
In estimating the rate of SBI, 2 of 2641 in our population (0.08%; 95%
CI, 0.009%-0.27%), we strictly defined SBI as bacterial meningitis, sepsis,
or death due to an infectious cause within 2 weeks of illness. We included
children who did not have a blood culture performed in the ED (group 2) in
the denominator when we calculated the rate of SBI. This could lead to underestimation
of the true rate of SBI. However, both of the children with SBI had blood
cultures performed in the ED (group 1), and there were no cases of SBI in
group 2. Therefore, our estimate represents the true SBI rate in our entire
population. As noted previously, Children's Hospital of Wisconsin is the only
freestanding children's hospital in the state and accounts for most of the
pediatric admissions in the region. In addition, all children with fever are
routinely contacted by telephone within 48 hours by the ED follow-up nurse.
Although the chance of losing patients to follow-up existed, it would be highly
unlikely for an SBI to occur at any outside facility without involving our
system.
Part of the success of our approach may be attributable to use of a
continuously monitoring blood culture system21
with around-the-clock notification, which allows most of the pathogenic OB
to be detected within 18 hours. This is consistent with the results of another
recently published study.13 Furthermore, we
have an effective callback system in the ED with a dedicated nurse in place
before implementing the clinical practice protocol for febrile children aged
2 to 36 months. As a result, follow-up was achieved within 8 hours of the
time of report of OB in our study population (median, 3.1 hours; quartile
range, 2.4-3.4 hours).
The 3% rate of OB in our study (95% CI, 2.2%-4.2%), and the distribution
of causative organisms, is consistent with recently reported data.13, 19 As in another study13
performed since the introduction of the H influenzae
type b vaccine in the United States, no cases of invasive H influenzae type b infection were reported in our population.
Because blood cultures were not performed universally in patients with
a temperature between 39.0°C and 40.9°C, our estimate of the rate
of OB may be biased. When we compared our practice pattern with the 1993 practice
guidelines, we found that only 46% of our eligible patients had a blood culture
performed in the ED. However, because our study population may be considered,
according to published guidelines, at high risk for OB based on temperature
alone, the anticipated effect of any such bias would be to inflate the apparent
rate of OB. An additional limitation is our reliance on hospital discharge
diagnosis to identify patients with fever. All patients who had blood culture
performed, as listed in the laboratory database, were successfully identified
by discharge diagnosis, suggesting that our diagnosis coding is consistent.
It is possible that some otherwise eligible patients who did not have blood
culture performed may have been missed. This would, however, lead to an underestimate
of the true population at risk (denominator) and again would have the effect
of overestimating the rate of OB.
The rate of contamination in our study (3.2%) is also consistent with
previously published rates.22-23
This rate gains significance as we found that the rates of performing a second
blood culture and rates of hospitalization were similar in patients with a
pathogenic OB and with contaminated growth in blood, resulting in higher health
care costs.24-26
The effect of these false-positive results must be considered as part of the
decision-making process in managing FWS.27-29
Our study provides up-to-date data on the effectiveness of a selective,
expectant approach to patients with FWS. The low risk of SBI is similar to
that reported with empiric antibiotic treatment. We believe that ensuring
adequate follow-up and withholding antibiotic administration until culture
results are known is a safe practice for children with FWS at risk for OB.
Such an approach could decrease unnecessary antibiotic use, believed to be
a contributory factor to the emergence of resistant S pneumoniae in certain communities across the United States.30
It is believed that the widespread use of conjugate pneumococcal vaccine
in the future will likely lead to a rapid and sustained drop in the rate of
OB in children.31 The introduction of the conjugate
pneumococcal vaccine may be the first step toward a new era, when the issue
of empiric antibiotics and OB will finally be resolved.32
| What This Study Adds
Children aged 2 to 36 months with suspected OB are at risk of developing
SBIs. Bacterial meningitis and sepsis, although rare events, are the outcomes
that frequently drive empiric antibiotic treatment in children with suspected
OB. Previous recommendations, based on results of earlier studies, suggest
empiric treatment to prevent SBI in children at risk for OB. The results of
this study suggest that an expectant approach rather than unnecessary empiric
antibiotic treatment is effective without any increase in adverse outcome.
When blood samples taken from children with FWS and suspected OB are analyzed
in a modern, continuously monitored blood culturing system, and those children
can be contacted to return promptly for follow-up, then the rates of bacterial
meningitis, sepsis, and death are not different from those in previously published
literature that used antibiotics empirically.
|
|
AUTHOR INFORMATION
Accepted for publication January 10, 2002.
We thank Marc H. Gorelick, MD, MSCE, and Christine M. Walsh-Kelly, MD,
for their contribution to manuscript preparation and Sue C. Kehl, PhD, for
her assistance with the microbiology laboratory database.
Corresponding author and reprints: Subhankar Bandyopadhyay, MD, Department
of Pediatrics, Medical College of Wisconsin, 9000 W Wisconsin Ave, Mailstop
677, Milwaukee, WI 53226 (e-mail: sbandy{at}mcw.edu).
From the Section of Emergency Medicine, Department of Pediatrics, Medical
College of Wisconsin (Drs Bandyopadhyay, Blackwell, and Hennes and Ms Bergholte),
and the Children's Hospital of Wisconsin (Dr Friedlander), Kenosha.
REFERENCES
| |
1. Fleisher GR, Ludwig S. Textbook of Pediatric Emergency Medicine. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000.
2. Jaffe DM. Occult bacteremia in children. Adv Pediatr Infect Dis. 1994;9:237-260.
PUBMED
3. Kuppermann N, Fleisher GR, Jaffe DM. Predictors of occult pneumococcal bacteremia in young febrile children. Ann Emerg Med. 1998;31:679-687.
FULL TEXT
|
ISI
| PUBMED
4. Baraff LJ, Lee SI. Fever without source: management of children 3 to 36 months of age. Pediatr Infect Dis J. 1992;11:146-151.
ISI
| PUBMED
5. Shapiro ED, Aaron NH, Wald ER, Chiponis D. Risk factors for development of bacterial meningitis among children
with occult bacteremia. J Pediatr. 1986;109:15-19.
FULL TEXT
|
ISI
| PUBMED
6. Joffe M, Avner JR. Follow-up of patients with occult bacteremia in pediatric emergency
departments. Pediatr Emerg Care. 1992;8:258-261.
ISI
| PUBMED
7. Baraff LJ, Oslund S, Prather M. Effect of antibiotic therapy and etiologic microorganism on the risk
of bacterial meningitis in children with occult bacteremia. Pediatrics. 1993;92:140-143.
FREE FULL TEXT
8. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for the management of infants and children 0 to
36 months of age with fever without source: Agency for Health Care Policy
and Research. Ann Emerg Med. 1993;22:1198-1210 [published correction appears in
Ann Emerg Med. 1993;22:1490].
FULL TEXT
9. Bass JW, Steele RW, Wittler RR, et al. Antimicrobial treatment of occult bacteremia: a multicenter cooperative
study. Pediatr Infect Dis J. 1993;12:466-473.
ISI
| PUBMED
10. Jaffe DM, Tanz RR, Davis AT, Henretig F, Fleisher G. Antibiotic administration to treat possible occult bacteremia in febrile
children. N Engl J Med. 1987;317:1175-1180.
ABSTRACT
11. Fleisher GR, Rosenberg N, Vinci R, et al. Intramuscular versus oral antibiotic therapy for the prevention of
meningitis and other bacterial sequelae in young, febrile children at risk
for occult bacteremia. J Pediatr. 1994;124:504-512.
FULL TEXT
|
ISI
| PUBMED
12. Carroll WL, Farrell MK, Singer JI, Jackson MA, Lobel JS, Lewis ED. Treatment of occult bacteremia: a prospective randomized clinical trial. Pediatrics. 1983;72:608-612.
FREE FULL TEXT
13. Alpern ER, Alessandrini EA, Bell LM, Shaw KN, McGowan KL. Occult bacteremia from a pediatric emergency department: current prevalence,
time to detection, and outcome. Pediatrics. 2000;106:505-511.
FREE FULL TEXT
14. Bulloch B, Craig WR, Klassen TP. The use of antibiotics to prevent serious sequelae in children at risk
for occult bacteremia: a meta-analysis. Acad Emerg Med. 1997;4:679-683.
ISI
| PUBMED
15. Rothrock SG, Green SM, Harper MB, Clark MC, McIlmail DP, Bachur R. Parenteral vs oral antibiotics in the prevention of serious bacterial
infections in children with Streptococcus pneumoniae
occult bacteremia: a meta-analysis. Acad Emerg Med. 1998;5:599-606.
ISI
| PUBMED
16. Belfer RA, Gittelman MA, Muniz AE. Management of febrile infants and children by pediatric emergency medicine
and emergency medicine: comparison with practice guidelines. Pediatr Emerg Care. 2001;17:83-87.
FULL TEXT
|
ISI
| PUBMED
17. Jacobs RF. Judicious use of antibiotics for common pediatric respiratory infections. Pediatr Infect Dis J. 2000;19:938-943.
ISI
| PUBMED
18. Preventing emerging infectious diseases: a strategy for the 21st century:
overview of the updated CDC plan. MMWR Recomm Rep. 1998;47(RR-15):1-14.
19. Lee GM, Harper MB. Risk of bacteremia for febrile young children in the post–Haemophilus influenzae type B era. Arch Pediatr Adolesc Med. 1998;152:624-628.
FREE FULL TEXT
20. Schutzman SA, Petrycki S, Fleisher GR. Bacteremia with otitis media. Pediatrics. 1991;87:48-53.
FREE FULL TEXT
21. Krisher KK, Whyburn DR, Koepnick FE. Comparison of the BacT/Alert pediatric blood culture system, Pedi-BacT,
with conventional culture using the 20-milliliter Becton-Dickinson supplemented
peptone broth tube. J Clin Microbiol. 1993;31:793-797.
FREE FULL TEXT
22. McGown JE, Bratton L, Klein JO, Finland M. Bacteremia in febrile children seen in a "walk-in" pediatric clinic. N Engl J Med. 1973;288:1309-1312.
23. Teele DW, Pelton SI, Grant MJ, et al. Bacteremia in febrile children under 2 years of age: results of cultures
of blood of 600 consecutive febrile children seen in a "walk-in" clinic. J Pediatr. 1975;87:227-230.
FULL TEXT
|
ISI
| PUBMED
24. Thuler LC, Jenicek M, Turgeon JP, Rivard M, Lebel P, Lebel MH. Impact of a false positive blood culture result on the management of
febrile children. Pediatr Infect Dis J. 1997;16:846-851.
FULL TEXT
|
ISI
| PUBMED
25. Weinbaum FI, Lavie S, Danek M, Sixsmith D, Heinrich GF, Mills SS. Doing it right the first time: quality improvement and the contaminant
blood culture. J Clin Microbiol. 1997;35:563-565.
ABSTRACT
26. Kornberg AE, Jain N, Dannenhoffer R. Evaluation of false positive blood cultures: guidelines for early detection
of contaminated cultures in febrile children. Pediatr Emerg Care. 1994;10:20-22.
FULL TEXT
|
ISI
| PUBMED
27. Leiu TA, Schwartz JS, Jaffe DM, Fleisher GR. Strategies for diagnoses and treatment of children at risk for occult
bacteremia: clinical effectiveness and cost-effectiveness. J Pediatr. 1991;118:21-29.
FULL TEXT
|
ISI
| PUBMED
28. Downs SM, McNutt RA, Margolis PA. Management of infants at risk for occult bacteremia: a decision analysis. J Pediatr. 1991;118:11-20.
FULL TEXT
|
ISI
| PUBMED
29. Yamamoto LG, Worthley RG, Melish ME, Seto DS. A revised decision analysis of strategies in the management of febrile
children at risk for occult bacteremia. Am J Emerg Med. 1998;16:193-207.
FULL TEXT
|
ISI
| PUBMED
30. Campbell GD, Silberman R. Drug-resistant Streptococcus pneumoniae. Clin Infect Dis. 1998;26:1188-1195.
ISI
| PUBMED
31. Lee GM, Fleisher GR, Harper MB. Management of febrile children in the age of conjugate pneumococcal
vaccine: a cost-effectiveness analysis. Pediatrics. 2001;108:835-844.
FREE FULL TEXT
32. King JC, Vink PE, Farley JJ, Smilie M, Parks M, Lichenstein R. Safety and immunogenicity of three doses of a five-valent pneumococcal
conjugate vaccine in children younger than two years with and without human
immunodeficiency virus infection. Pediatrics. 1997;99:575-580.
FREE FULL TEXT
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Updated Review of Blood Culture Contamination
Hall and Lyman
Clin. Microbiol. Rev. 2006;19:788-802.
ABSTRACT
| FULL TEXT
Incidence of Occult Bacteremia Among Highly Febrile Young Children in the Era of the Pneumococcal Conjugate Vaccine: A Study From a Children's Hospital Emergency Department and Urgent Care Center
Stoll and Rubin
Arch Pediatr Adolesc Med 2004;158:671-675.
ABSTRACT
| FULL TEXT
Management of Febrile Children in the Conjugate Pneumococcal Vaccine Era
Gabriel et al.
CLIN PEDIATR 2004;43:75-82.
ABSTRACT
Empiric Antibiotics for Suspected Infant Outpatient Bacteremia: Unnecessary?
JWatch Infect. Diseases 2002;2002:3-3.
FULL TEXT
Support for Expectant Management of Highly Febrile Young Children
JWatch General 2002;2002:4-4.
FULL TEXT
|
