Short Antibiotic Treatment for Coagulase-negative Staphylococcal Sepsis in Premature Infants: A Multicenter Noninferiority Study

Background: – Optimizing antibiotic duration in neonatal intensive care units is essential for antimicrobial stewardship and microbiome preservation. However, the safety of short antibiotic courses for uncomplicated late-onset coagulase-negative staphylococcal (CoNS) sepsis remains uncertain. Aim: – To determine whether short (≤96 hours) antibiotic treatment of uncomplicated CoNS sepsis in premature infants admitted to a neonatal intensive care unit is noninferior to long treatment (>96 hours) by comparing relapse rates. Methods: – This multicenter, observational cohort study reviewed all proven neonatal CoNS sepsis in premature births <32 weeks admitted to 8 neonatal intensive care units in the Netherlands between 2017 and 2020. Uncomplicated CoNS sepsis was defined as clinical recovery within 24–48 hours, no central venous line in place or removed after the onset of sepsis, no signs of necrotizing enterocolitis or infected thrombus, and no Staphylococcus lugdunensis bacteremia. Data on patient characteristics, antibiotic treatment and relapse rates were systematically collected. The incidence of relapse (<72 hours after discontinuation of treatment) was calculated as the proportion (%) of the total. The noninferiority margin was set at 2%. A P_{noninferiority} value <0.025 was considered significant. Results: – A total of 669 proven late-onset CoNS sepsis were identified. Of these, 390 were uncomplicated. Among uncomplicated cases, 172 were treated ≤96 hours and 218 >96 hours. Patient characteristics showed no significant differences. One relapse occurred in the short-treatment group (0.58%), none in the long-treatment group, with a significant P_{noninferiority} value of 0.007. Conclusions: – The relapse rate in uncomplicated CoNS sepsis was extremely low (<1%), even with short-course treatment. In premature infants with uncomplicated CoNS sepsis, shorter antibiotic treatment is noninferior to longer treatment, confirming its safety and effectiveness.