Comparing early-onset sepsis risk: risk calculator, American Academy of Pediatrics guidelines, and local care

Abstract Background Early-onset neonatal sepsis (EONS) is a major concern in at-risk term and late preterm infants. The American Academy of Pediatrics (AAP) recommends categorical risk assessment (CRA), the sepsis risk calculator (SRC), or serial observation. We compared a local protocol initiating antibiotics only with predefined clinical signs together with abnormal interleukin-6 (IL-6) and/or C-reactive protein (CRP) with modeled CRA- and SRC-recommendations. Methods Retrospective cohort of neonates ≥34 weeks with ≥1 EONS risk factors at Vienna General Hospital (February–July 2024). Infants were managed per local protocol; CRA and SRC were applied retrospectively. Primary outcomes were blood sampling and empiric antibiotics. Given the single culture-positive case, diagnostic performance metrics were treated as exploratory and descriptive. Results Among 184 infants, 43 (23%) had clinical signs and 1 (0.5%) had positive blood-culture. Under the local protocol, 56 (30%) underwent blood sampling, and 25 (14%) received antibiotics. CRA and SRC would have recommended empiric antibiotics for 46 (25%) and 36 (20%) infants, respectively. Thus, the local protocol increased sampling but reduced antibiotic exposure. Conclusions In this low-incidence cohort, the local protocol reduced empiric antibiotic exposure compared with CRA and SRC; findings primarily inform specificity/stewardship and do not support conclusions regarding sensitivity or clinical safety. Impact In at-risk neonates ≥34 weeks’ gestation, a biomarker-augmented local protocol was associated with lower empiric antibiotic use than AAP categorical risk assessment and the sepsis risk calculator in this low-incidence cohort. This real-world study from a European tertiary center directly compares three endorsed EONS strategies within the same contemporary cohort. Combining structured risk assessment with selective biomarker testing may support antimicrobial stewardship, but the limited specificity of biomarkers at applied thresholds requires careful interpretation alongside the clinical presentation.