Implementation of a 24-hour empiric antibiotic duration for negative early-onset sepsis evaluations to reduce early antibiotic exposure in premature infants

Objective: Antibiotic exposure increases the risk of morbidity and mortality in premature infants. Many centers use at least 48 hours of antibiotics in the evaluation of early-onset sepsis (EOS, <72 hours after birth), yet most important pathogens grow within 24 hours. We investigated the safety and efficacy of reducing empiric antibiotic duration to 24 hours. Design: Quality improvement study. Setting: A tertiary-care neonatal intensive care unit. Patients: Inborn infants <35 weeks gestational age at birth (ie, preterm) admitted January 2019 through December 2020. Intervention: In December 2019, we changed the recommended duration of empiric antibiotics for negative EOS evaluations from 48 hours to 24 hours. Results: Patient characteristics before and after the intervention were similar. After the intervention, 71 preterm infants (57%) with negative EOS evaluations received ≤24 hours of antibiotics, an increase from 15 (10%) before the intervention. These 71 infants comprised 77% of infants with negative EOS blood cultures after excluding those treated as clinical sepsis (≥5 days of antibiotics). For all negative EOS blood cultures, the mean treatment duration decreased by 0.5 days from 3.9 days to 3.4 days. This finding equated to 2.4 fewer antibiotic days per 100 patient days for negative EOS blood cultures but similar antibiotic days per 30 patient days (7.2 days vs 7.5 days). This measure did not change over time. Subsequent sepsis evaluations <7 days after a negative EOS blood culture did not increase. Excluding contaminants, the median time to positivity was 13.2 hours (range, 8-23) in 8 positive blood cultures. Conclusion: Implementation of a 24-hour antibiotic course for negative EOS evaluations safely reduced antibiotic exposure in 77% of infants <35 weeks gestational age at birth in whom EOS was ruled out. All clinically significant pathogens grew within 24 hours.