Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia
Authors: Giannoni Eric , Dimopoulou Varvara , Klingenberg Claus , Navér Lars , Nordberg Viveka , Berardi Alberto , el Helou Salhab , Fusch Gerhard , Bliss Joseph M. , Lehnick Dirk , Guerina Nicholas , Seliga-Siwecka Joanna , Maton Pierre , Lagae Donatienne , Mari Judit , Janota Jan , Agyeman Philipp K. A. , Pfister Riccardo , Latorre Giuseppe , Maffei Gianfranco , Laforgia Nicola , Mózes Enikő , Størdal Ketil , Strunk Tobias , Stocker Martin ,   AENEAS Study Group, Capretti Maria Grazia , Ceccoli Martina , De Angelis Morena , Drimaco Pietro , Eap Khalyane , el Helou Zoe , Esmaeilizand Rana , Foglianese Alessandra , Geraci Carmelo , Grochowski Bartłomiej , Håkansson Stellan , Kaur Sharandeep , Kollegger Anne-Louise , Oldendorff Frida , Rizzo Vittoria , Rønnestad Arild E. , Shrestha Damber , Stensvold Hans Jørgen , Torregrossa Anaïs , Trefny Martin , Zilinska Kristyna , Zwijacz Aleksandra 
Published: November 2022

ImportanceAppropriate 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.ObjectiveTo compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries.Design, Setting, and ParticipantsThis 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.ExposuresExposure to antibiotics started in the first postnatal week.Main Outcomes and MeasuresThe 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.ResultsA 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 RelevanceThe 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.