Early Discontinuation of Empiric Antibiotics in the Neonatal Intensive Care Unit: A Stewardship Perspective on Culture-negative Neonatal Sepsis

A BSTRACT Culture-negative neonatal sepsis is a major clinical challenge in neonatal intensive care units and occurs substantially more frequently than culture-confirmed sepsis. This narrative review synthesizes current evidence on the early discontinuation of empiric antibiotics in neonates with suspected but unconfirmed sepsis, with particular attention to antimicrobial stewardship programme (ASP) strategies. ASPs can improve antibiotic use by supporting timely reassessment, de-escalation, and discontinuation. In clinically stable infants with negative blood cultures, discontinuation of empiric antibiotics at 36–48 h is supported by current guidance. Biomarkers such as procalcitonin (PCT) and C-reactive protein (CRP), together with decision-support tools such as the neonatal early-onset sepsis calculator for eligible infants, may complement clinical assessment. However, concern about occult infection can make clinicians reluctant to stop treatment. The application of these strategies in low- and middle-income countries may also be constrained by limited diagnostic infrastructure.