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 first postnatal week.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 first postnatal week were classified as culture-negative cases
treated for ≥5 days (CN ≥ 5d), culture-negative cases treated for <5 days (CN < 5d),
or CP-EOS cases.Out of 757,979 infants, 21,703 (2.9%) received intravenous antibiotics.
The number of infants classified 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.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.In a study of 757,979 infants born
in high-income countries, we report a presumed culture-negative early-onset sepsis
incidence of 10.6/1000 livebirths with an associated antibiotic exposure of 77 antibiotic
days per 1000 livebirths. This study sheds light on the major contribution of presumed
culture-negative early-onset sepsis to early-life antibiotic exposure. Given the diagnostic
uncertainty surrounding culture-negative early-onset sepsis, the low mortality rate,
and the disproportionate antibiotic exposure associated with this condition, our study
emphasizes the importance of targeting culture-negative early-onset sepsis in antimicrobial
stewardship programs.
