Early-onset neonatal sepsis and neonatal antibiotic exposure in Hungary a nationwide population-based study

Neonatal sepsis remains a challenge in perinatal medicine. We aimed to estimate incidence of culture positive early-onset sepsis (CP-EOS), causative pathogens and overall antibiotic exposure in newborn infants in Hungary. Retrospective national registry analysis (2020-2023). Data were mainly collected from the Hungarian National Perinatal Registry covering all level II-III neonatal intensive care units (NICUs) in Hungary. The number of livebirths in each gestational age group was provided by Hungarian Central Statistical Office. Overall CP-EOS incidence was 0.41/1,000 livebirths (0.20/1,000 ≥ 35 weeks gestation, 7.0/1,000 < 35 weeks gestation). Main pathogens were Escherichia coli (33.3%) and Group B streptococci -GBS (24.5%). Ten of 49 (20.4%) infants with E. coli sepsis died. No GBS related mortality occurred. Lumbar puncture was only performed in 30/147 (20.4%) of the CP-EOS cases. No cases of isolated meningitis occurred in the absence of CP-EOS. Newborns presenting with respiratory distress in the first 72 h were five times more likely to receive antibiotics (OR 4.9 CI 4.6-5.2) than infants without respiratory distress. Overall, 63.9% of NICU-treated neonates received antibiotics for a median (IQR) duration of 5 (3-8) days. A minimum of 3.2% of all neonates in Hungary received antibiotics, acknowledging that some more neonates are treated on postnatal wards and Level I NICUs which are not included in the perinatal registry. A substantial number (15.6%) of blood cultures were taken without subsequent antibiotic commencement.

Our results provide the first national incidence estimates for CP-EOS in Central-Eastern Europe. The study identified high antibiotic use with a concurrently relatively low EOS incidence. The results support implementing new strategies to reduce unnecessary antibiotic exposure in the newborn period.

• Neonatal early-onset sepsis (EOS) causes substantial neonatal morbidity, prompting widespread, frequent empirical antibiotic use. • Unnecessary early-life antibiotic exposure shifts the infant gut microbiota and increases risks for long-term adverse health outcomes.

• This first nationwide Central-Eastern European study reveals a low EOS incidence (0.41/1,000 live births) but high NICU antibiotic exposure (63.9%) in Hungary. • Escherichia coli has overtaken GBS as the leading EOS pathogen, causing significant mortality primarily in preterm infants.