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. 2022 Nov 1;5(11):e2243691.
doi: 10.1001/jamanetworkopen.2022.43691.

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

Eric Giannoni  1 , Varvara Dimopoulou  1 , Claus Klingenberg  2   3 , Lars Navér  4 , Viveka Nordberg  4 , Alberto Berardi  5 , Salhab El Helou  6 , Gerhard Fusch  6 , Joseph M Bliss  7 , Dirk Lehnick  8 , Nicholas Guerina  7 , Joanna Seliga-Siwecka  9 , Pierre Maton  10 , Donatienne Lagae  11 , Judit Mari  12 , Jan Janota  13   14   15 , Philipp K A Agyeman  16 , Riccardo Pfister  17 , Giuseppe Latorre  18 , Gianfranco Maffei  19 , Nicola Laforgia  20 , Eniko Mózes  21 , Ketil Størdal  22 , Tobias Strunk  23 , Martin Stocker  24 ; AENEAS Study Group
Collaborators, Affiliations

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

Eric Giannoni et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Berardi reported receiving personal fees from Atheneum Partners, GmbH outside the submitted work. Dr Bliss reported receiving personal fees from Mead Johnson Nutrition outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Burden of Treatment
A, Proportion of infants treated with antibiotics (error bars denote 95% CIs) in each network. B, Duration of antibiotic treatment (error bars denote 95% CIs) in infants with early-onset sepsis and in infants without early-onset sepsis. The 239 patients who died were not included in this graph. C, Number of antibiotic days per 1000 live births (error bars denote 95% CIs) in each network. D, Number of antibiotic days per 1000 live births by year for each network. The dashed lines represent the median of the 13 networks.
Figure 2.
Figure 2.. Burden of Disease
A, Incidence of all culture-proven early-onset sepsis (EOS) episodes and incidence calculated without inclusion of coagulase-negative staphylococci (CoNS) cases in each network are shown (error bars denote 95% CIs). B, All-cause mortality and mortality in EOS cases per 1000 live births (error bars denote 95% CIs) in each network are shown. The dashed lines represent the median of the 13 networks.
Figure 3.
Figure 3.. Burden of Treatment vs Burden of Disease
Relationship between the incidence of early-onset sepsis and exposure to antibiotics in each network. The size of the bubbles represents the number of births. The dashed lines represent the median of the 13 networks.
See this image and copyright information in PMC

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