Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study

BACKGROUND Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the rst postnatal week. METHODS We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia. All late-preterm and term infants born between 2014 and 2018 who received intravenous antibiotics during the rst postnatal week were classi ed as culture-negative cases treated for ≥5 days (CN ≥ 5d), culture-negative cases treated for <5 days (CN < 5d), or CP-EOS cases. RESULTS Out of 757,979 infants, 21,703 (2.9%) received intravenous antibiotics. The number of infants classi ed as CN ≥ 5d, CN < 5d, and CP-EOS was 7996 (37%), 13,330 (61%), and 375 (1.7%). The incidence of CN ≥ 5d, CN < 5d, and CP-EOS was 10.6 (95% CI 10.3–10.8), 17.6 (95% CI 17.3–17.9), and 0.49 (95% CI 0.44–0.54) cases per 1000 livebirths. The median (IQR) number of antibiotic days administered for CN ≥ 5d, CN < 5d, and CP-EOS was 77 (77–78), 53 (52–53), and 5 (5-5) per 1000 livebirths. CONCLUSIONS CN ≥ 5d substantially contributed to the overall antibiotic exposure, and was 21-fold more frequent than CP-EOS. Antimicrobial stewardship programs should focus on shortening antibiotic treatment for culture-negative cases.