Antibiotic stewardship in the context of management of early onset neonatal sepsis-an evolving paradigm shift

Abstract

Early onset neonatal sepsis (EOS) is a rare but potentially life-threatening condition in term and late preterm infants. Clinicians face the challenge of promptly identifying and treating the small subset of neonates with true sepsis, while avoiding unnecessary intervention in the majority who remain unaffected. The clinical overlap between sepsis and normal physiological adaptation in the first 72 hours of life, combined with the limitations of current diagnostic modalities, has historically led to a culture of presumed safety, resulting in the overtreatment of many healthy infants with antibiotics. Such early antibiotic exposure is associated with numerous invasive procedures, disruption of mother-infant bonding, increased healthcare utilisation, and significant costs. Moreover, the global rise of antibiotic resistance, the slow pace of novel antibiotic development, and growing concerns regarding microbiome dysgenesis and its long-term health consequences have catalysed a paradigm shift. Neonatal antibiotic stewardship now stands as a cornerstone of EOS management, seeking to balance the imperative for rapid, effective therapy against the risks of antimicrobial overuse. This review traces the evolution of antibiotic stewardship within neonatal care, highlighting the development and implementation of risk-based guidelines and strategies and decision-support models designed to curtail inappropriate antibiotic use without compromising clinical safety. By synthesising contemporary evidence and practice innovations, we emphasise the necessity for ongoing evaluation and refinement of stewardship approaches to optimise outcomes for neonates at risk of EOS. The journey of neonatal antibiotic stewardship is dynamic and ongoing, demanding sustained collaboration, research, and a commitment to safe, evidence-based clinical practice.

Keywords: Infant; Newborn; Early-onset neonatal sepsis; Neonatal antibiotics; Antibiotic stewardship; Sepsis risk calculator; Serial physical examination; Antimicrobial resistance

Core Tip: Early-onset neonatal sepsis is rare yet fear of missed serious infection continues to drive widespread empirical antibiotic use, exposing large numbers of well newborns to avoidable harm. This review synthesises contemporary evidence underpinning the paradigm shift in neonatal antibiotic stewardship, critically comparing traditional categorical guidelines with multivariate risk prediction tools and serial physical examination strategies. By integrating epidemiology, emerging United Kingdom and international data, and evolving clinical practice, it provides practical insights into how antibiotic exposure can be safely reduced without compromising outcomes, supporting more precise, family-centred, and evidence-based care.