Full Title: Diagnosis and Management of Febrile Infants (0–3 Months)
The febrile infant is a common clinical problem that accounts for a large number of
ambulatory care visits. Young febrile infants (age 0–3 months) often present with nonspecific
symptoms and it is difficult to distinguish between infants with a viral syndrome and those with
early serious bacterial illness. This evidence report is designed to review the literature about the management of the febrile infant and to identify needs for future research.
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- To review the evidence for diagnostic accuracy of screening for serious bacterial illness (SBI) and invasive herpes simplex virus (HSV) infection in febrile infants 3 months or younger.
- To ascertain harms and benefits of various management strategies.
- To compare prevalence of SBI and HSV between different clinical settings.
- To determine how well the presence of viral infection predicts against SBI.
- To review evidence on parental compliance to return for followup assessments (infants less than 6 months).
Data Sources: MEDLINE, CINAHL, Embase, Cochrane Central Register of Controlled Trials,
the Cochrane Database of Systematic Reviews, abstracts, and unpublished materials.
Review Methods: Two independent reviewers screened the literature and extracted data on
population characteristics, index/diagnostic test characteristics. Diagnostic test accuracy studies
were assessed using Quality Assessment of Diagnostic Accuracy Studies.
Results: Eighty-four original studies were included. The combined clinical and laboratory
criteria (Rochester, Philadelphia, Boston, and Milwaukee) demonstrated similar overall accuracy
(sensitivity: 84.4 percent to 100.0 percent; specificity: 26.6 percent to 69.0 percent; negative
predictive value: 93.7 percent to 100.0 percent; and positive predictive value: 3.3 percent to 48.6
percent) for identifying infants with SBI. The criteria based on history of recent immunization or
rapid influenza test demonstrated higher sensitivity but lower specificity compared with criteria
based on age, gender, and the degree of fever. The overall accuracy of C-reactive protein was
greater than that for absolute neutrophil count and absolute band counts , white blood cell, and
For correctly identifying infants with and without SBI (or bacteremia), the Boston,
Philadelphia, and Milwaukee criteria/protocol showed better overall accuracy when applied to
older infants versus neonates. The Rochester criteria were more accurate in neonates than in
- Evidence on HSV was scarce.
- Most of the criteria/protocols demonstrated high negative predictive values and low positive predictive values for correctly predicting the absence or presence of SBI.
- In studies reporting outcomes of delayed treatment for infants with SBI initially classified as low risk, all infants recovered uneventfully. The reported adverse events following immediate antibiotic therapy were limited to drug related rash and infiltration of intravenous line.
- There was a higher prevalence of SBI in infants without viral infection or clinical bronchiolitis compared to infants with viral infection or bronchiolitis.
- The prevalence of SBI tended to be higher in the emergency departments versus primary care setting offices.
- The parental compliance to followup for return visits/reassessment of infants after initial
examination across four studies ranged from 77.4 percent to 99.8 percent. There was no evidence
to determine the influence of parental factors and clinical settings on the degree of parental
Conclusions: Overall, the focus of the literature has been on ruling out SBI. Harms associated
with testing or management strategies have been less well studied. Combined criteria showed
fairly high sensitivity and (therefore) reliability in not missing possible cases of SBI. Attempts to
identify high-risk groups specifically, described in a minority of reports, were not as successful.
There is very little literature on factors associated with compliance to followup care, although
that information could be crucial to improving management strategies in the low-risk group.
Future studies should focus on identifying the risks associated with testing and management
strategies and factors that predict compliance.
Diagnosis and Management of Febrile Infants (0–3 Months)
Evidence-based Practice Center: University of Ottawa EPC
Current as of March 2012
Diagnosis and Management of Febrile Infants, Structured Abstract. March 2012. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/tp/febrinftp.htm