Antibiotic Exposure for suspected Neonatal EArly-onset Sepsis

JAMA Network Open. 2022;5(11):e2243691

DOI: 10.1001/jamanetworkopen.2022.43691


Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aiming at safely reducing neonatal antibiotic exposure.

To compare early postnatal exposure to antibiotics, incidence of EOS and mortality among different networks in high-income countries.


design, setting and participants

This is a retrospective, cross-sectional study in late-preterm and term infants born between January 1,2014 and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe, North-America, and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022.

Exposure to antibiotics started in the first postnatal week.


main outcomes and measures

The main outcomes were the proportion of late-preterm and term infants receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality

A total of 757979 late-preterm and term infants were born in the participating networks during the study period, 21’703 (2.86%, 95% CI 2.83-2.90), including 12’886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18 to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for infants with EOS, and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days/1000 live births (range across networks 54-491 days per 1000 live births). The incidence of EOS was 0.49/1000 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered.


conclusions and relevance

The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS, and there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early-life.

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