Antibiotic use and early-onset sepsis in newborn infants

Abstract

Antibiotic therapy for neonatal early-onset sepsis (EOS) is life-saving, but its inappropriate use in uninfected newborns may cause harm. The aim of this thesis was to investigate antibiotic use, the incidence of EOS, associated morbidity and mortality among neonates in Sweden, and to evaluate a guideline designed to reduce unwarranted antibiotic use. Medical records were reviewed in Study I, while Study II-IV were based on data from the Swedish Neonatal Quality register (SNQ). Study I assessed a quality improvement initiative and demonstrated that implementation of a revised clinical guideline was associated with a reduction in the median duration of antibiotic therapy and hospital stay by two days (p < 0.001), without reinfections or deaths. Annual healthcare costs decreased by approximately €122 000 among neonates with culture-negative suspected EOS who met the guideline criteria. Studies II and III were nationwide observational studies including 1 025 515 late preterm and term infants born from 2012 to 2020. These studies quantified antibiotic use in the first week of life, the incidence of EOS and mortality in Sweden. In study II, 1.9% of newborns received antibiotics in the first week of life. The incidence of EOS was 0.63 per 1000 live births, and mortality associated with EOS was 1.4%. Study III, demonstrated substantial regional and unit variation in antibiotic use (regions 1.3%-3.0%; units 0.9%-4.3%). Regional variation in EOS incidence and all-cause mortality ranged from 0.33 to 0.93 per 1000 and 0.21 to 0.54 per 1000 live births, respectively. Study IV was a nationwide observational study including 5757 very preterm infants born during 2017-2024. Empirical antibiotic use during the first week after birth was associated with increased odds of severe morbidity and mortality during hospitalisation. Conclusions: Antibiotic use in the first week of life substantially exceeds the incidence of EOS among late preterm and term infants in Sweden, with marked regional and unit variations. The incidence of EOS has declined over time in this population. In very preterm infants, early empirical antibiotic therapy was associated with increased odds for adverse outcomes. Targeted antimicrobial stewardship initiatives may contribute to reducing unwarranted antibiotic use while maintaining safety.