Background: Despite development of risk stratification tools decades ago, the best strategy
for evaluation and management of young infants with fever without a clear source remains uncertain.
Objective: To describe the variability in current practice and review recently published evidence in three
key areas: inflammatory markers were used as a tool for risk stratification, impact of viral testing, and
optimal observation time on antibiotics.
Method: Articles were identified using PubMed, Scopus, and Cochrane databases and via experts. Abstracts
were screened and potential articles underwent full review if they focused on febrile infants 0-
90 days with fever without a source and outcomes for key topics.
Results: Thirty-two articles were included. Recent studies show that variability exists for most aspects
of evaluation and management. C reactive protein and procalcitonin (PCT) perform poorly for identification
of serious bacterial infections (SBIs). However, PCT has good diagnostic accuracy for detection
of invasive bacterial infections (IBIs), such as bacteremia and meningitis. When PCT is combined
with urinalysis and clinical appearance in the Step-by-Step method, the sensitivity for detection of IBI
is 92% for infants > 21 days of age. Infants with lab-confirmed viral infection were found to have reduced
risk for SBI. Blood culture yield for true pathogens was the highest in the first 12-36 hours after
Conclusion: Recent studies suggest viral testing and inflammatory markers (specifically PCT) can
help better stratify young febrile infants at risk for IBIs. Infants who are deemed low risk may benefit
from shorter observation times and tailored or discontinued antibiotic therapy.