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.

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OBJECTIVES We aimed to study whether national and local antibiotic stewardship projects have reduced the antibiotic use in newborns and to monitor potential changes in adverse outcomes. METHODS In a nationwide, population-based study from Norway, we included all hospital live births from 34 weeks' gestation (n = 282 046) during 2015 to 2019. The primary outcome was the proportion of newborns treated with antibiotics from 0 to 28 days after birth. The secondary outcomes were the overall duration of antibiotic treatment and by categories: culture-positive sepsis, clinical sepsis, and no sepsis. RESULTS A total of 7365 (2.6%) newborns received intravenous antibiotics during the period, with a reduction from 3.1% in 2015 to 2.2% in 2019 (30% decrease; P < .001). Hospitals with antibiotic stewardship projects experienced the largest reduction (48% vs 23%; P < .001). We found a small decrease in the median duration of antibiotic treatment in newborns without sepsis from 2.93 to 2.66 days (P = .011), and geographical variation was reduced during the study period. The overall number of days with antibiotic treatments was reduced by 37% from 2015 to 2019 (119.1 of 1000 vs 75.6 of 1000; P < .001). Sepsis was confirmed by blood culture in 206 newborns (incidence rate: 0.73 cases per 1000 live births). We found no increase in sepsis with treatment onset >72 hours of life, and sepsis-attributable deaths remained at a low level. CONCLUSIONS During the study period, a substantial decrease in the proportion of newborns treated with antibiotics was observed together with a decline in treatment duration for newborns without culture-positive sepsis.

Aim: To study whether a simple targeted intervention could reduce unwarranted antibiotic treatment in near-term and term neonates with suspected, but not confirmed early-onset sepsis. Methods: A quality improvement initiative in three Norwegian neonatal intensive care units. The intervention included an inter-hospital clinical practice guideline for discontinuing antibiotics after 36-48 hours if sepsis was no longer suspected and blood cultures were negative in neonates ≥ 34+0 weeks of gestation. Two units used procalcitonin in decision-making. We compared data 12-14 months before and after guideline implementation. The results are presented as median with interquartile ranges. Results: A total of 284 infants (2.5% of all births ≥ 34+0 weeks of gestation) received antibiotics before and 195 (1.8%) after guideline implementation (P = .0018). The two units that used procalcitonin discontinued antibiotics earlier after guideline implementation than the unit without procalcitonin. Neonates not diagnosed with sepsis were treated 49 (31-84) hours before and 48 (36-72) hours after guideline implementation (P = .68). In all infants, including those diagnosed with sepsis, antibiotic treatment duration was reduced from 108 (60-144) to 96 (48-120) hours (P = .013). Conclusion: Antibiotic treatment duration for suspected, but not confirmed earlyonset sepsis did not change. However, treatment duration for all infants and the proportion of infants commenced on antibiotics were reduced.