A tailored approach to neonatal early-onset sepsis: an Italian collaborative guidance document

Background Italian indications for Early-Onset Sepsis (EOS) prevention and management are lacking. A national survey (2024–2025) on clinical practices revealed marked heterogeneity among centers, excessive reliance on biomarkers and frequent empirical treatments among asymptomatic infants. These gaps prompted the development of national, evidence-based consensus indications to standardize care and reduce unnecessary antibiotic exposure. Methods A task force of experts of the Italian Society of Neonatology developed indications through a consensus process. The panel reviewed international guidelines, available evidence, and clinical practice standards to formulate pragmatic indications for the management of neonates ≥ 35 weeks’ gestation at risk for EOS. Results Indications were issued and summarized in a decalogue. Key principles included: Prioritizing clinical assessment over traditional risk factors; Suggesting close serial clinical observation (without antibiotics) in asymptomatic neonates with risk factors; Relying on blood and/or cerebrospinal fluid culture for EOS diagnosis; Incorporating routine lumbar puncture into the diagnostic work-up when EOS is suspected; Avoiding the use of surface cultures for EOS diagnosis; Avoiding reliance on biomarkers for the diagnosis of EOS and for guiding antibiotic therapy; Promptly initiating empiric antibiotics in symptomatic neonates regardless of risk factors; Reassessing empiric therapy at 36 hours from culture collection: discontinuing antibiotics at 36 hours when cultures are sterile and the clinical course is reassuring; Promptly de-escalating to targeted, narrow-spectrum therapy when a pathogen is isolated from cultures; Suggesting that infants with isolated, mild and transient respiratory signs can be managed with close observation without laboratory testing or antibiotics. Conclusions These expert-driven indications provide a standardized, evidence-based framework for EOS management in Italy. By emphasizing early clinical recognition and judicious antibiotic use, the indications aim to unify practice across centres and enhance antimicrobial stewardship for neonates ≥ 35 weeks’ gestation.