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.
Empiric antibiotic exposure for 5 or more days in preterm neonates born before 29 weeks' gestation was associated with an increased risk of NEC.
Objective To determine the delivery efficiency of budesonide aerosol via a mesh nebulizer in a neonatal ventilator model. Design/Method In an in‐vitro ventilated neonatal model, budesonide suspension was administered using a mesh nebulizer. A collection filter was placed distal to the endotracheal tube and budesonide captured by the filter was measured using UV spectroscopy. The ventilator was, in turn, either on high frequency or conventional ventilation mode and the nebulizer was placed either proximal (close to the endotracheal tube) or distal (between the wet side of humidifier and the inspiratory circuit). Each combination (nebulizer position and ventilation mode) to assess budesonide delivery was tested five times. Results Overall delivery of budesonide to the distal end of the endotracheal tube a small percentage of the total dose administered. The deposition with conventional ventilation was 2.12% (±1.06) and 1.26% (±0.27), with proximal and distal placement of the nebulizer, respectively. With high‐frequency ventilation, the deposition percentages were 1.82% (±0.82) and 1.69% (±0.23), with proximal and distal nebulizer placement, respectively. Conclusion Only a small percentage of administered budesonide is delivered to the distal endotracheal tube, irrespective of ventilation mode, and nebulizer placement.
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