Current Evidence on the Evaluation and Management of Fever Without a Source in Infants Aged 0-90 Days: A Review

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 incubation. 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. Keywords: C reactive protein, fever, infant, neonate, procalcitonin, serious bacterial infection.