Scientific article
Open access

Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia

Published inJAMA network open, vol. 5, no. 11, e2243691
Publication date2022-11-01
First online date2022-11-01

Importance: 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 aimed at safely reducing neonatal antibiotic exposure.

Objective: 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 of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and 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.

Exposures: Exposure to antibiotics started in the first postnatal week.

Main outcomes and measures: The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality.

Results: A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (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 neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 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 that 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.

  • Infant, Newborn
  • Infant
  • Male
  • Humans
  • Neonatal Sepsis / drug therapy
  • Neonatal Sepsis / epidemiology
  • Anti-Bacterial Agents / therapeutic use
  • Retrospective Studies
  • Cross-Sectional Studies
  • Australia
  • North America / epidemiology
Citation (ISO format)
GIANNONI, Eric et al. Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia. In: JAMA network open, 2022, vol. 5, n° 11, p. e2243691. doi: 10.1001/jamanetworkopen.2022.43691
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Article (Published version)
ISSN of the journal2574-3805

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