[Skip to Navigation]
Sign In
January 2002

Ampicillin Use in Infant Fever: A Systematic Review

Author Affiliations

From the Divisions of General Academic Pediatrics (Dr Brown) and Infectious Disease (Dr Burns), Department of Pediatrics, and Department of Epidemiology, School of Public Health and Community Medicine (Dr Cummings), University of Washington School of Medicine, Seattle.

Arch Pediatr Adolesc Med. 2002;156(1):27-32. doi:10.1001/archpedi.156.1.27

Objectives  To estimate the prevalence of perinatal Listeria monocytogenes and enterococcal infections in outpatient febrile infants and to evaluate the need to treat with ampicillin.

Data Sources  Online bibliographies were searched for articles related to serious bacterial infection and fever in infants. Reference lists from selected and review articles were also examined.

Study Selection  Studies that reported rates and types of bacterial infection in febrile outpatients younger than 3 months were included. Those performed outside North America, lacking results by age, or those that evaluated selected patient populations were excluded.

Data Extraction  Two authors independently reviewed the selected articles for inclusion and abstracted the data.

Data Synthesis  Fourteen studies, evaluating 5247 febrile outpatients, were included. The prevalences of L monocytogenes and enterococcal infections were 7.3 (binomial exact 95% confidence interval [CI], 3.5-13.3), 1.9 (95% CI, 0.6-4.4), and 5.6 (95% CI, 0.7-2.1) per 1000 febrile infants in the first, second, and third months of life, respectively. To cover 1 infant with serious bacterial infection caused by L monocytogenes and enterococcal infections, the numbers of febrile infants who would need ampicillin were estimated as 138 (95% CI, 76-288) in the first month, 527 (95% CI, 226-1621) in the second month, and 178 (95% CI, 50-1469) in the third month. Enterococcal infections occurred in all ages studied; there were no Listeria infections after 30 days of age.

Conclusion  The empirical use of ampicillin to cover febrile infants for L monocytogenes and enterococcal infections is most justifiable in the first month of life.

THE MANAGEMENT of febrile infants varies by age. A third-generation cephalosporin is most commonly used as a single agent in older infants for both possible sepsis and meningitis, when empirical treatment is indicated.1 In neonates, most treatment recommendations include ampicillin in empirical coverage to cover Listeria monocytogenes or enterococcal infections. There is limited evidence to determine the optimal age at which ampicillin therapy is no longer needed as a part of empirical antibiotic regimens. Recently, it has been suggested that ampicillin may be excluded from the empirical regimen for infants younger than 60 days.2 Our study was undertaken to determine the incidence of bacteremia and/or bacterial meningitis (B/BM) and serious bacterial infection (SBI) caused by organisms that are best treated with ampicillin in febrile infants younger than 3 months of age presenting to emergency departments and outpatient clinics.

Ampicillin is commonly used in 2 regimens: for the empirical treatment of (1) neonatal sepsis (ampicillin plus an aminoglycoside) and (2) neonatal meningitis (ampicillin plus a third-generation cephalosporin). Its inclusion is generally suggested to improve coverage for L monocytogenes, and there is the additional potential benefit of coverage for infections caused by enterococcus. Neither of these organisms is susceptible to the cephalosporins. Either ampicillin plus an aminoglycoside or a third-generation cephalosporin alone provides excellent empirical coverage against the most common neonatal pathogens, group B streptococcus and Escherichia coli.3

Although enterococcal infections are generally believed to be acquired after birth, L monocytogenes is thought to be perinatally acquired. Thus, it is commonly assumed that an infant's risk of listeriosis diminishes with increased postnatal age. In 8 population-based studies4-11 with adequate data for analysis, 340 (95%) of 357 confirmed cases of L monocytogenes occurred in the first 30 days of life.4-11 However, it does not necessarily follow that febrile outpatient infants are more likely to have L monocytogenes if they present in the first month vs subsequent months, since their fever changes their risk of bacterial disease compared with the general population. Other perinatally acquired infections, such as group B streptococcus and E coli, may also decrease over time; thus, the proportion of febrile infants with L monocytogenes could theoretically be constant during the first few months of life.

We conducted a systematic literature review to estimate the prevalence of L monocytogenes and enterococcal infections among febrile infants in the first, second, and third months of life. We used this information to estimate the number of febrile infants who would need empirical ampicillin therapy to provide prompt, appropriate antibiotic coverage for 1 infant infected with these bacteria.


Bacteremia and/or bacterial meningitis was defined as all bacterial infections identified in either blood or cerebrospinal fluid (CSF). Serious bacterial infection was defined as all bacterial infections with an identified bacterial source, including urinary tract, skin, and bone infections but excluding pneumonia.

Two bibliographic databases, MEDLINE and the Cochrane Controlled Trials Register, were searched in December 2000 for the following terms: (1) serious bacterial infection.tw (tw indicates textword) or *bacterial infection (* indicates explode of a medical subject heading) or *sepsis or *bacteremia and (2) *fever or fever.tw or febrile.tw and (3) limited to "newborn" or "infant." In addition, references from included studies and recent review articles were reviewed. Studies were included if they evaluated febrile infants younger than 3 months in any outpatient setting (emergency department, clinic, or physician's office) for the presence of bacterial infection. All authors' definitions of fever were accepted. At least 75% of study infants needed to have blood and CSF cultures performed to be analyzed for B/BM, and, in addition, 75% needed to have urine cultures performed to be analyzed for SBI. The studies had to report the prevalence of L monocytogenes or enterococcal infection according to patient age in either 4-week or 1-month intervals. Studies were excluded if they evaluated only a subset of febrile infants (eg, low-risk infants). If there were multiple studies from the same institution with overlapping enrollment periods, then the studies were selected to include the largest independent population of infants.

One of us (J.C.B.) evaluated study titles and abstracts and retrieved the full text of all studies that might include infants younger than 3 months. All studies that contained data on bacterial infections in infants up to 3 months of age were then blinded to author and journal for review by the second author (J.L.B.). Both authors independently determined which studies met inclusion and exclusion criteria. Disagreements were resolved by discussion, and consensus was achieved in the selection of articles for analysis. Attempts were made to contact study authors when small amounts of additional information would allow their studies to be included. Data were then independently abstracted by both reviewers.

Estimates were made for 3 categories of age in 1-month blocks. Prevalences between groups were compared using the Fisher exact test. Within each age group, we estimated the prevalence of Listeria and enterococcal infections by dividing the total number of these infections by the total number studied. We calculated exact 95% binomial confidence intervals. These may be thought of as intervals for fixed-effects estimates, which assume that the underlying prevalence of Listeria and enterococcal infections was the same in all studies.

We also used bias-corrected bootstrap methods to generate 95% confidence intervals.12,13 First, we sampled within each study to account for within-study variation. Second, we sampled the studies themselves to account for between-study variation. These may be thought of as intervals for random-effects estimates, which allow for the possibility that the true prevalence of Listeria and enterococcal infections differed across studies. Analyses were done using Stata statistical software.14

Finally, we estimated how many febrile children must receive empirical therapy with ampicillin to provide prompt empirical treatment for 1 child with Listeria and enterococcal infections. This was simply the inverse of the prevalence estimates and may be thought of as the number needed to cover (NNC).


An estimated 4000 references were reviewed, including 2761 references from the initial MEDLINE search, all references from the identified studies of febrile infants younger than 3 months, and all references from recent review articles.2,15-31

Ninety-two studies2,32-4041-5051-6061-7071-8081-9091-100101-110111-122 were found to have a potentially relevant population. Attempts were made to contact 7 study authors33,43,50,57,71,110,118 to obtain additional data, with 5 responses; 2 of these authors33,50 provided additional information.

Ultimately, 14 studies met criteria for inclusion (Table 1).32-45 Nine studies were prospective, and 5 were retrospective. The definition of fever ranged from a rectal temperature of 38.0°C or higher measured either at home or at the treating institution to 38.2°C or higher measured at the institution. Patients were evaluated in the emergency department in 8 studies, in either the emergency department or a hospital clinic in 2 studies, and in a hospital outpatient area in 4 studies. Age groupings varied between studies by up to 4 days. Body fluid culture rates varied by study and source between 90% and 100%, with 11 studies reporting that 100% of patients had blood, urine, and CSF cultures performed. One study, included in the analysis of B/BM, reported that all infants younger than 2 months had blood cultures performed and most had CSF cultures performed.45

Table 1. 
Listeria monocytogenes and Enterococcal Infections in Included Studies*
Listeria monocytogenes and Enterococcal Infections in Included Studies*

In total, there were 5 infections caused by L monocytogenes and 12 infections caused by enterococci among 5247 infants studied (data regarding urine cultures were missing in 3 studies). No L monocytogenes or enterococcal infections were reported in sources other than blood, urine, and CSF, and there were no L monocytogenes cultures positive in urine specimens. The oldest infant with a L monocytogenes infection was 30 days of age and had both bacteremia and bacterial meningitis. This infant was included in the second month category because the child was in the 29- to 56-day-old infant group reported by Baker et al.33 Enterococcal infections were found in all 3 body fluids and all age groups.

The prevalence of L monocytogenes and enterococcal infections and the number of children who would need empirical treatment with ampicillin to cover for one of these infections are presented by age in Table 2. The prevalences of B/BM were similar in the first and third months of life and lower in the second month of life (P = .02 for comparison between the 3 months).

Table 2. 
Prevalence of Listeria monocytogenes and Enterococcal Infection by Age and Source of Infection*
Prevalence of Listeria monocytogenes and Enterococcal Infection by Age and Source of Infection*

The incidence of perinatal listeriosis is reported to be decreasing.2 We did not find evidence of this in our review of febrile infants. When the 3 most recent studies32,33,41 were evaluated separately, the rates of Listeria infection were similar, with 2 Listeria infections reported in 1048 infants younger than 60 days. Based on 2 of these studies32,41 that evaluated infants younger than 1 month, the NNCs to empirically treat Listeria or enterococcal infections were 313 and 126 for B/BM and SBI, respectively.


In a recent study, Sadow et al2 reevaluated the use of empirical ampicillin for suspected invasive bacterial infections in infants 60 days or younger.2 They concluded that ampicillin was not a crucial component of empirical antibiotic therapy, since Listeria is of diminishing importance as a pathogen in this age group and enterococcal infections are generally confined to the urinary tract. They proposed changing empirical antibiotic coverage in this age range to gentamicin and a third-generation cephalosporin, with the addition of ampicillin for those patients with positive findings on initial CSF examination.

Our results, in contrast, support current practice. We believe the use of ampicillin to cover for Listeria and enterococcal infections is still justified in the first month of life. In this age range, 1 in every 439 outpatient infants with fever will have a L monocytogenes infection, which causes high morbidity and mortality, potentially benefiting from expedient therapy with ampicillin. In addition, 1 in every 585 and 345 febrile infants will be appropriately treated for enterococcal B/BM and SBI, respectively. We believe it is reasonable to empirically treat a large number of infants, all of whom we would hospitalize in any event, in an effort to promptly treat those few who have Listeria and enterococcal infections.

Studies included in this review had 1-month age definitions that ranged from 28 to 30 days. Since there was 1 infant 30 days of age with L monocytogenes bacteremia and meningitis, it seems reasonable to choose 30 days of age as a cutoff for empirical ampicillin use.

Between 31 and 60 days of age, we believe the NNCs for B/BM (1544) and SBI (527) may be too large to merit adding ampicillin to empirical therapy for all infants, when empirical therapy is indicated. In this age group, the empirical use of ampicillin in addition to a third-generation cephalosporin would primarily improve coverage of enterococcal infections, most of which would involve the urinary tract. We agree with the recommendation of Sadow et al to add ampicillin if CSF findings are suggestive of meningitis and their alternate proposal to add ampicillin if urine gram stain identifies gram-positive cocci or a gram stain is unavailable but urinalysis is highly suggestive of infection. In addition, we would advocate that ampicillin be considered for any infant who appears very ill or septic, to empirically treat for the rare, but nevertheless possible, Listeria or enterococcal bacteremia.

Surprisingly, the prevalence of reported L monocytogenes and enterococcal infections was greater among infants in their third month of life compared with those in the second month. This may reflect increased rates of enterococcal urinary tract infections in the third month compared with the second month of life. It could also be a result of referral bias, if well-appearing febrile infants in the second month of life are more likely to be referred to the emergency department than are similar infants in the third month of life. Given the small number of studies involving infants in the third month of life, confidence intervals surrounding these estimates were large, although the differences in prevalence rates were statistically significant. Although the numbers needed to treat were similar in the first and third months of life, only enterococcal infections would have been undertreated if ampicillin had not been given empirically in the third month of life. We suggest that empirical ampicillin treatment for infants in the third month of life be determined using the same criteria applied to the infants in the second month of life.

Many authors advocate withholding any antibiotics for low-risk infants after the first month of life. Our study was not intended to determine when empirical treatment is warranted, but rather when ampicillin should be added to an empirical regimen. Institutions where only a subset of febrile infants receive empirical antibiotic treatment will likely have higher rates of bacterial infection in the treated group, likely including an increased proportion of Listeria and enterococcal infections. The NNCs might be lower in this subset.

This review has a number of limitations. The potential benefit of empirical ampicillin use could be overestimated if ampicillin is less than 100% efficacious in treating or ameliorating the course of Listeria and enterococcal infections. The potential benefit could be underestimated if there were Listeria and enterococcal infections that did not result in positive cultures or if other serious bacterial illnesses, such as pneumonia, cellulitis, or osteomyelitis, were caused by these infections. In addition, 5 of the 14 studies had culture rates less than 100%, so they may have underreported the prevalence of bacterial infection. We were unable to evaluate specific characteristics of the infants with positive Listeria or enterococcal cultures, because this information was typically not available.

During the analysis, we were concerned that studies without positive cultures would be more likely to have adequate information for inclusion than would studies with cultures positive for Listeria and enterococcal infections. However, no articles were excluded that identified patients in 1-month blocks and did not specify the ages of the infants with positive cultures. One included study43 could not be analyzed for SBI because it mentioned 2 enterococcal urinary tract infections that could not be categorized by age. On the other hand, 4 studies57,71,110,118 were excluded because they did not break down infants into 1-month age groups, and none of these studies had infants with cultures positive for Listeria and enterococcal infections.

Our findings generally support the current practice at our institution, which includes empirical use of ampicillin for febrile infants in the first 4 weeks of life. Empirical ampicillin in this age range is particularly important in institutions such as ours that routinely use this drug in combination with an aminoglycoside, since it will additionally provide improved coverage for group B streptococcus. Infants in the second and third months of life with suspected pyelonephritis also frequently receive treatment with ampicillin in addition to either gentamicin or a third-generation cephalosporin, pending culture results. Our findings in this review may encourage us to consider ampicillin for the occasional febrile infant in the second and third months of life with gram-positive cocci on CSF gram stain or a septic appearance.

Accepted for publication July 12, 2001.

We thank Robert Davis, MD, MPH, and Fred Rivara, MD, MPH, for their encouragement and thoughtful critique of the manuscript and Gini Scott for her administrative assistance.

Corresponding author and reprints: Julie C. Brown, MD, Children's Hospital and Regional Medical Center, 4800 Sand Point Way NE, PO Box 5371/CH-04, Seattle, WA 98105-0371 (e-mail: jbrow1@chmc.org).

Editor's Note: What This Study Adds

Febrile infants are at risk for serious bacterial infection. Ampicillin is often used in empirical treatment primarily to cover L monocytogenes and enterococcal infections. This systematic review provides evidence to support the common practice of empirical ampicillin treatment for febrile infants younger than 1 month and additionally recommends ampicillin for a selected subset of febrile infants in the second and third months of life.

Baraff  LJBass  JWFleisher  GR  et al.  Practice guideline for the management of infants and children 0 to 36 months of age with fever without source.  Ann Emerg Med. 1993;221198- 1210Google ScholarCrossref
Sadow  KBDerr  RTeach  SJ Bacterial infections in infants 60 days and younger: epidemiology, resistance, and implications for treatment.  Arch Pediatr Adolesc Med. 1999;153611- 614Google ScholarCrossref
Odio  CM Cefotaxime for treatment of neonatal sepsis and meningitis.  Diagn Microbiol Infect Dis. 1995;22111- 117Google ScholarCrossref
McLauchlin  J Human listeriosis in Britain, 1967-85, a summary of 722 cases, I: listeriosis during pregnancy and in the newborn.  Epidemiol Infect. 1990;104181- 189Google ScholarCrossref
McLauchlin  J Human listeriosis in Britain, 1967-85, a summary of 722 cases, II: listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence.  Epidemiol Infect. 1990;104191- 201Google ScholarCrossref
Gellin  BGBroome  CV Listeriosis.  JAMA. 1989;2611313- 1320Google ScholarCrossref
Mascola  LSorvillo  FNeal  JIwakoshi  KWeaver  R Surveillance of listeriosis in Los Angeles County, 1985-1986: a first year's report.  Arch Intern Med. 1989;1491569- 1572Google ScholarCrossref
Jones  EMMcCulloch  SYReeves  DSMacGowan  AP A 10 year survey of the epidemiology and clinical aspects of listeriosis in a provincial English city.  J Infect. 1994;2991- 103Google ScholarCrossref
Albritton  WLWiggins  GLFeeley  JC Neonatal listeriosis: distribution of serotypes in relation to age at onset of disease.  J Pediatr. 1976;88481- 483Google ScholarCrossref
Bowmer  EJMcKiel  JACockcroft  WHSchmitt  NRappay  DE Listeria monocytogenes infections in Canada.  Can Med Assoc J. 1973;109125- 129Google Scholar
Varughese  PCarter  A Human listeriosis surveillance in Canada—1987.  Can Dis Wkly Rep. 1988;14151- 155Google Scholar
Efron  BTibishirani  RJ An Introduction to the Bootstrap.  New York, NY Chapman & Hall1993;
Lunneborg  CE Data Analysis by Resampling: Concepts and Applications.  Pacific Grove, Calif Duxbury2000;
Stata Corp, Stata Statistical Software: Release 7.0.  College Station, Tex Stata Corp2001;
Baker  MD Evaluation and management of infants with fever.  Pediatr Clin North Am. 1999;461061- 1072Google ScholarCrossref
Baraff  LJOslund  SASchriger  DLStephen  ML Probability of bacterial infections in febrile infants less than three months of age: a meta-analysis.  Pediatr Infect Dis J. 1992;11257- 264Google ScholarCrossref
Baskin  MN The prevalence of serious bacterial infections by age in febrile infants during the first 3 months of life.  Pediatr Ann. 1993;22462- 466Google ScholarCrossref
Bonadio  WA The history and physical assessments of the febrile infant.  Pediatr Clin North Am. 1998;4565- 77Google ScholarCrossref
Bonadio  WA Evaluation and management of serious bacterial infections in the febrile young infant.  Pediatr Infect Dis J. 1990;9905- 912Google ScholarCrossref
Gehlbach  SH Fever in children younger than three months of age: a pooled analysis.  J Fam Pract. 1988;27305- 312Google Scholar
Jaskiewicz  JAMcCarthy  CA Evaluation and management of the febrile infant 60 days of age or younger.  Pediatr Ann. 1993;22477- 480Google ScholarCrossref
Klassen  TPRowe  PC Selecting diagnostic tests to identify febrile infants less than 3 months of age as being at low risk for serious bacterial infection: a scientific overview.  J Pediatr. 1992;121671- 676Google ScholarCrossref
Lieu  TABaskin  MNSchwartz  JSFleisher  GR Clinical and cost-effectiveness of outpatient strategies for management of febrile infants.  Pediatrics. 1992;891135- 1144Google Scholar
Lynn  RRWiebe  RA Initial approach to the infant younger than 2 months of age who presents with fever.  Semin Pediatr Infect Dis. 1995;6212- 217Google ScholarCrossref
Neto  GMoyer  VAed Fever in the young infant.  Evidence Based Pediatrics and Child Health London, England BMJ Books2000;178- 188Google Scholar
Nozicka  CA Evaluation of the febrile infant younger than 3 months of age with no source of infection.  Am J Emerg Med. 1995;13215- 218Google ScholarCrossref
Powell  KR Evaluation and management of febrile infants younger than 60 days of age.  Pediatr Infect Dis J. 1990;9153- 157Google ScholarCrossref
Sectish  TC Management of the febrile infant.  Pediatr Ann. 1996;25608- 613Google ScholarCrossref
Singer  JIVest  JPrints  A Occult bacteremia and septicemia in the febrile child younger than two years.  Emerg Med Clin North Am. 1995;13381- 416Google Scholar
Slater  MKrug  SE Evaluation of the infant with fever without source: an evidence based approach.  Emerg Med Clin North Am. 1999;1797- 126Google ScholarCrossref
Young  PC The management of febrile infants by primary-care pediatricians in Utah: comparison with published practice guidelines.  Pediatrics. 1995;95623- 627Google Scholar
Baker  MDBell  LM Unpredictability of serious bacterial illness in febrile infants from birth to 1 month of age.  Arch Pediatr Adolesc Med. 1999;153508- 511Google Scholar
Baker  MDBell  LMAvner  JR The efficacy of routine outpatient management without antibiotics of fever in selected infants.  Pediatrics. 1999;103627- 631Google ScholarCrossref
Baker  MDBell  LMAvner  JR Outpatient management without antibiotics of fever in selected infants.  N Engl J Med. 1993;3291437- 1441Google ScholarCrossref
Bonadio  WASmith  DSSabnis  S The clinical characteristics and infectious outcomes of febrile infants aged 8 to 12 weeks.  Clin Pediatr (Phila). 1994;3395- 99Google ScholarCrossref
Bonadio  WAHagen  ERucka  J  et al.  Efficacy of a protocol to distinguish risk of serious bacterial infection in the outpatient evaluation of febrile young infants.  Clin Pediatr (Phila). 1993;32401- 404Google ScholarCrossref
Bonadio  WAWebster  HWolfe  AGorecki  D Correlating infectious outcome with clinical parameters of 1130 consecutive febrile infants aged zero to eight weeks.  Pediatr Emerg Care. 1993;984- 86Google ScholarCrossref
Broner  CWPolk  SASherman  JM Febrile infants less than eight weeks old: predictors of infection.  Clin Pediatr (Phila). 1990;29438- 443Google ScholarCrossref
Caspe  WBChamudes  OLouie  B The evaluation and treatment of the febrile infant.  Pediatr Infect Dis. 1983;2131- 135Google ScholarCrossref
Ferrera  PCBartfield  JMSnyder  HS Neonatal fever: utility of the Rochester criteria in determining low risk for serious bacterial infections.  Am J Emerg Med. 1997;15299- 302Google ScholarCrossref
Kadish  HALoveridge  BTobey  JBolte  RGCorneli  HM Applying outpatient protocols in febrile infants 1-28 days of age: can the threshold be lowered?  Clin Pediatr (Phila). 2000;3981- 88Google ScholarCrossref
King Jr  JCBerman  EDWright  PF Evaluation of fever in infants less than 8 weeks old.  South Med J. 1987;80948- 952Google ScholarCrossref
Krober  MSBass  JWPowell  JMSmith  FRSeto  DS Bacterial and viral pathogens causing fever in infants less than 3 months old.  AJDC. 1985;139889- 892Google Scholar
Roberts  KBBorzy  MS Fever in the first eight weeks of life.  Johns Hopkins Med J. 1977;1419- 13Google Scholar
Wasserman  GMWhite  CB Evaluation of the necessity for hospitalization of the febrile infant less than three months of age.  Pediatr Infect Dis J. 1990;9163- 169Google ScholarCrossref
Anbar  RDRichardson–de Corral  VO'Malley  PJ Difficulties in universal application of criteria identifying infants at low risk for serious bacterial infection.  J Pediatr. 1986;109483- 485Google ScholarCrossref
Antonow  JAHansen  KMcKinstry  CAByington  CL Sepsis evaluations in hospitalized infants with bronchiolitis.  Pediatr Infect Dis J. 1998;17231- 236Google ScholarCrossref
Baskin  MNO'Rourke  EJFleisher  GR Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone.  J Pediatr. 1992;12022- 27Google ScholarCrossref
Baskin  MNO'Rourke  EJFleisher  GR Management of febrile infants (FI) 15 to 28 days of age with intramuscular (IM) ceftriaxone (CTX) and one day of inpatient observation [abstract].  AJDC. 1992;146377Google Scholar
Baskin  MNFleisher  GRO'Rourke  EJ Outpatient management of febrile infants (FI) 28 to 90 days of age with intramuscular ceftriaxone (CTX).  AJDC. 1990;144419- 420Google Scholar
Baker  MDBell  LMAvner  JR The efficacy of non-invasive in-hospital and outpatient management of febrile infants: a four year experience.  AJDC. 1991;145418- 419Google Scholar
Baker  MDAvner  JRBell  LM Failure of infant observation scales in detecting serious illness in febrile, 4- to 8-week-old infants.  Pediatrics. 1990;851040- 1043Google Scholar
Barnett  EDBauchner  HTeele  DWKlein  JO Serious bacterial infections in febrile infants and children selected for lumbar puncture.  Pediatr Infect Dis J. 1994;13950- 953Google ScholarCrossref
Bauchner  HPhilipp  BDashefsky  BKlein  JO Prevalence of bacteriuria in febrile children.  Pediatr Infect Dis J. 1987;6239- 242Google ScholarCrossref
Berger  RMBerger  MYvan Steensel-Moll  HADzoljic-Danilovic  GDerksen-Lubsen  G A predictive model to estimate the risk of serious bacterial infections in febrile infants.  Eur J Pediatr. 1996;155468- 473Google ScholarCrossref
Berkowitz  CDUchiyama  NTully  SB  et al.  Fever in infants less than two months of age: spectrum of disease and predictors of outcome.  Pediatr Emerg Care. 1985;1128- 135Google ScholarCrossref
Bonadio  WAHennes  HSmith  D  et al.  Reliability of observation variables in distinguishing infectious outcome of febrile young infants.  Pediatr Infect Dis J. 1993;12111- 114Google ScholarCrossref
Bonadio  WASmith  DCarmody  J Correlating CBC profile and infectious outcome: a study of febrile infants evaluated for sepsis.  Clin Pediatr (Phila). 1992;31578- 582Google ScholarCrossref
Bonadio  WAMcElroy  KJacoby  PLSmith  D Relationship of fever magnitude to rate of serious bacterial infections in infants aged 4-8 weeks.  Clin Pediatr (Phila). 1991;30478- 480Google ScholarCrossref
Bonadio  WALehrmann  MHennes  H  et al.  Relationship of temperature pattern and serious bacterial infections in infants 4 to 8 weeks old 24 to 48 hours after antibiotic treatment.  Ann Emerg Med. 1991;201006- 1008Google ScholarCrossref
Bonadio  WAHegenbarth  MZachariason  M Correlating reported fever in young infants with subsequent temperature patterns and rate of serious bacterial infections.  Pediatr Infect Dis J. 1990;9158- 160Google ScholarCrossref
Bonadio  WARomine  KGyuro  J Relationship of fever magnitude to rate of serious bacterial infections in neonates.  J Pediatr. 1990;116733- 735Google ScholarCrossref
Bonadio  WA Incidence of serious infections in afebrile neonates with a history of fever.  Pediatr Infect Dis J. 1987;6911- 914Google ScholarCrossref
Bramson  RTMeyer  TLSilbiger  MLBlickman  JGHalpern  E The futility of the chest radiograph in the febrile infant without respiratory symptoms.  Pediatrics. 1993;92524- 526Google Scholar
Brik  RHamissah  RShehada  NBerant  M Evaluation of febrile infants under 3 months of age: is routine lumbar puncture warranted?  Isr J Med Sci. 1997;3393- 97Google Scholar
Brook  IGruenwald  LD Occurrence of bacteremia in febrile children seen in a hospital outpatient department and private practice.  South Med J. 1984;771240- 1242Google ScholarCrossref
Bulis  DCrain  EFGoldman  HBijur  P Is chest x-ray necessary in the evaluation of every febrile infant less than eight weeks of age?  AJDC. 1990;144446- 447Google Scholar
Byington  CLTaggart  EWCarroll  KCHillyard  DR A polymerase chain reaction–based epidemiologic investigation of the incidence of nonpolio enteroviral infections in febrile and afebrile infants 90 days and younger [serial online].  Pediatrics. 1999;103E27Google ScholarCrossref
Chiu  CHLin  TYBullard  MJ Application of criteria identifying febrile outpatient neonates at low risk for bacterial infections.  Pediatr Infect Dis J. 1994;13946- 949Google ScholarCrossref
Chiu  CHLin  TYBullard  MJ Identification of febrile neonates unlikely to have bacterial infections.  Pediatr Infect Dis J. 1997;1659- 63Google ScholarCrossref
Crain  EFShelov  SP Febrile infants: predictors of bacteremia.  J Pediatr. 1982;101686- 689Google ScholarCrossref
Crain  EFGershel  JCGoldman  R Usefulness of predictors of bacteremia in evaluation and management of febrile young infants [abstract].  AJDC. 1987;141377Google Scholar
Crain  EFGershel  JC Which febrile infants younger than two weeks of age are likely to have sepsis? a pilot study.  Pediatr Infect Dis J. 1988;7561- 564Google Scholar
Crain  EFGershel  JC Urinary tract infections in febrile infants younger than 8 weeks of age.  Pediatrics. 1990;86363- 367Google Scholar
Crain  EFBulas  DBijur  PEGoldman  HS Is a chest radiograph necessary in the evaluation of every febrile infant less than 8 weeks of age?  Pediatrics. 1991;88821- 824Google Scholar
Dagan  RPowell  KRHall  CBMenegus  MA Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis.  J Pediatr. 1985;107855- 860Google ScholarCrossref
Dagan  RSofer  SPhillip  MShachak  E Ambulatory care of febrile infants younger than 2 months of age classified as being at low risk for having serious bacterial infections.  J Pediatr. 1988;112355- 360Google ScholarCrossref
Dagan  RHall  CBPowell  KRMenegus  MA Epidemiology and laboratory diagnosis of infection with viral and bacterial pathogens in infants hospitalized for suspected sepsis.  J Pediatr. 1989;115351- 356Google ScholarCrossref
DeAngelis  CJoffe  AWillis  EWilson  M Hospitalization v outpatient treatment of young, febrile infants.  AJDC. 1983;1371150- 1152Google Scholar
Elzoobi  KHoff  CO'Connor  TGoebel  J Febrile infants without obvious fever source [letter] [published correction appears in Pediatr Emerg Care. 1997;13:295].  Pediatr Emerg Care. 1997;1385- 86Google Scholar
Freedman  RMIngram  DLGross  I  et al.  A half century of neonatal sepsis at Yale: 1928 to 1978.  AJDC. 1981;135140- 144Google Scholar
Ginsburg  CMMcCracken Jr  GH Urinary tract infections in young infants.  Pediatrics. 1982;69409- 412Google Scholar
Greene  JWHara  CO'Connor  SAltemeier  WA Management of febrile outpatient neonates.  Clin Pediatr (Phila). 1981;20375- 380Google ScholarCrossref
Hervas  JAAlomar  ASalva  FReina  JBenedi  VJ Neonatal sepsis and meningitis in Mallorca, Spain, 1977-1991.  Clin Infect Dis. 1993;16719- 724Google ScholarCrossref
Heulitt  MJAblow  RCSantos  CCO'Shea  TMHilfer  CL Febrile infants less than 3 months old: value of chest radiography.  Radiology. 1988;167135- 137Google Scholar
Hoberman  AChao  HPKeller  DM  et al.  Prevalence of urinary tract infection in febrile infants.  J Pediatr. 1993;12317- 23Google ScholarCrossref
Jaskiewicz  JAMcCarthy  CARichardson  ACPowell  KR Reevaluation of criteria to identify infants evaluated for possible sepsis (PS) at low risk (LR) for serious bacterial infection [abstract].  AJDC. 1992;146483Google Scholar
Jaskiewicz  JAMcCarthy  CARichardson  AC  et al. for the Febrile Infant Collaborative Study Group, Febrile infants at low risk for serious bacterial infection—an appraisal of the Rochester criteria and implications for management.  Pediatrics. 1994;94390- 396Google Scholar
Kellogg  JAFerrentino  FLGoodstein  MH  et al.  Frequency of low level bacteremia in infants from birth to two months of age.  Pediatr Infect Dis J. 1997;16381- 385Google ScholarCrossref
Klein  JOSchlesinger  PCKarasic  RB Management of the febrile infant three months of age or younger.  Pediatr Infect Dis. 1984;375- 79Google ScholarCrossref
Koenig  JMPatterson  LERench  MAEdwards  MS Role of fibronectin in diagnosing bacterial infection in infancy.  AJDC. 1988;142884- 887Google Scholar
Kum-Nji  PLuedtke  GSLeggiadro  RJ Bacterial blood and cerebrospinal fluid isolates in infants one to three months old [letter].  Pediatr Infect Dis J. 1995;14252- 253Google ScholarCrossref
Kuppermann  NBank  DEWalton  EASenac Jr  MOMcCaslin  I Risks for bacteremia and urinary tract infections in young febrile children with bronchiolitis.  Arch Pediatr Adolesc Med. 1997;1511207- 1214Google ScholarCrossref
Leggiadro  RJDarras  BT Viral and bacterial pathogens of suspected sepsis in young infants.  Pediatr Infect Dis. 1983;2287- 289Google ScholarCrossref
Liebelt  ELQi  KHarvey  K Diagnostic testing for serious bacterial infections in infants aged 90 days or younger with bronchiolitis.  Arch Pediatr Adolesc Med. 1999;153525- 530Google ScholarCrossref
Liu  CHLehan  CSpeer  ME  et al.  Early detection of bacteremia in an outpatient clinic.  Pediatrics. 1985;75827- 831Google Scholar
Losek  JDKishaba  RGBerens  RJBonadio  WAWells  RG Indications for chest roentgenogram in the febrile young infant.  Pediatr Emerg Care. 1989;5149- 152Google ScholarCrossref
Marcinak  JF Evaluation of children with fever greater than or equal to 104° F in an emergency department.  Pediatr Emerg Care. 1988;492- 96Google ScholarCrossref
Mathur  MShah  HDixit  K  et al.  Bacteriological profile of neonatal septicemia cases (for the year 1990-91).  J Postgrad Med. 1994;4018- 20Google Scholar
McCarthy  PLDolan  TF The serious implications of high fever in infants during their first three months: six years' experience at Yale–New Haven Hospital Emergency Room.  Clin Pediatr (Phila). 1976;15794- 796Google ScholarCrossref
McCarthy  PLJekel  JFStashwick  CA  et al.  Further definition of history and observation variables in assessing febrile children.  Pediatrics. 1981;67687- 693Google Scholar
McCarthy  PLSharpe  MRSpiesel  SZ  et al.  Observation scales to identify serious illness in febrile children.  Pediatrics. 1982;70802- 809Google Scholar
McCarthy  PLLembo  RMBaron  MAFink  HDCicchetti  DV Predictive value of abnormal physical examination findings in ill-appearing and well-appearing febrile children.  Pediatrics. 1985;76167- 171Google Scholar
McCarthy  PLLembo  RMFink  HDBaron  MACicchetti  DV Observation, history, and physical examination in diagnosis of serious illnesses in febrile children less than or equal to 24 months.  J Pediatr. 1987;11026- 30Google ScholarCrossref
McCarthy  CAPowell  KRJaskiewicz  JA  et al.  Outpatient management of selected infants younger than two months of age evaluated for possible sepsis.  Pediatr Infect Dis J. 1990;9385- 389Google ScholarCrossref
McGowan Jr  JEBratton  LKlein  JOFinland  M Bacteremia in febrile children seen in a "walk-in" pediatric clinic.  N Engl J Med. 1973;2881309- 1312Google ScholarCrossref
Metrou  MCrain  EF The complete blood count differential ratio in the assessment of febrile infants with meningitis.  Pediatr Infect Dis J. 1991;10334- 335Google ScholarCrossref
Metrou-Stein  MCrain  EF A second look at criteria for evaluating febrile infants [abstract].  Pediatr Emerg Care. 1990;6230Google Scholar
Ogborn  CJSoulen  JLDeAngelis  C Hospitalization vs outpatient treatment of young febrile infants: 10-year comparison.  Arch Pediatr Adolesc Med. 1995;14994- 97Google ScholarCrossref
O'Shea  JS Assessing the significance of fever in young infants: the diagnostic and prognostic value of cerebrospinal fluid and other clinical and laboratory findings.  Clin Pediatr (Phila). 1978;17854- 856Google ScholarCrossref
Pantell  RHNaber  MLamar  RDias  JK Fever in the first six months of life: risks of underlying serious infection.  Clin Pediatr (Phila). 1980;1977- 82Google ScholarCrossref
Patterson  RJBisset  GSKirks  DRVanness  A Chest radiographs in the evaluation of the febrile infant.  AJR Am J Roentgenol. 1990;155833- 835Google ScholarCrossref
Philip  AGHewitt  JR Early diagnosis of neonatal sepsis.  Pediatrics. 1980;651036- 1041Google Scholar
Philip  AG Detection of neonatal sepsis of late onset.  JAMA. 1982;247489- 492Google ScholarCrossref
Pichichero  METodd  JK Detection of neonatal bacteremia.  J Pediatr. 1979;94958- 960Google ScholarCrossref
Powell  KRMawhorter  SD Outpatient treatment of serious infections in infants and children with ceftriaxone.  J Pediatr. 1987;110898- 901Google ScholarCrossref
Richardson  ARoughman  KWhite  K Use of clinical observation scales to identify serious illness in febrile children [abstract].  AJDC. 1990;144435Google Scholar
Rosenberg  NVranesich  PCohen  S Incidence of serious infection in infants under age two months with fever.  Pediatr Emerg Care. 1985;154- 56Google ScholarCrossref
Schwartz  RHWientzen Jr  RL Occult bacteremia in toxic-appearing, febrile infants: a prospective clinical study in an office setting.  Clin Pediatr (Phila). 1982;21659- 663Google ScholarCrossref
Soman  M Characteristics and management of febrile young children seen in a university family practice.  J Fam Pract. 1985;21117- 122Google Scholar
Tetzlaff  TRAshworth  CNelson  JD Otitis media in children less than 12 weeks of age.  Pediatrics. 1977;59827- 832Google Scholar
Wright  PFThompson  JMcKee Jr  KT  et al.  Patterns of illness in the highly febrile young child: epidemiologic, clinical, and laboratory correlates.  Pediatrics. 1981;67694- 700Google Scholar