Varvara Dimopoulou, Claus Klingenberg, Lars Navér, Viveka Nordberg, Alberto Berardi, Salhab el Helou, Gerhard Fusch, Joseph M. Bliss, Dirk Lehnick, Nicholas Guerina, Joanna Seliga-Siwecka, Pierre Maton, Donatienne Lagae, Judit Mari, Jan Janota, Philipp K. A. Agyeman, Riccardo Pfister, Giuseppe Latorre, Gianfranco Maffei, Nicola Laforgia, Enikő Mózes, Ketil Størdal, Tobias Strunk, Martin Stocker, Eric Giannoni
{"title":"Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study","authors":"Varvara Dimopoulou, Claus Klingenberg, Lars Navér, Viveka Nordberg, Alberto Berardi, Salhab el Helou, Gerhard Fusch, Joseph M. Bliss, Dirk Lehnick, Nicholas Guerina, Joanna Seliga-Siwecka, Pierre Maton, Donatienne Lagae, Judit Mari, Jan Janota, Philipp K. A. Agyeman, Riccardo Pfister, Giuseppe Latorre, Gianfranco Maffei, Nicola Laforgia, Enikő Mózes, Ketil Størdal, Tobias Strunk, Martin Stocker, Eric Giannoni","doi":"10.1038/s41390-024-03532-6","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the first postnatal week.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia. All late-preterm and term infants born between 2014 and 2018 who received intravenous antibiotics during the first postnatal week were classified as culture-negative cases treated for ≥5 days (CN ≥ 5d), culture-negative cases treated for <5 days (CN < 5d), or CP-EOS cases.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Out of 757,979 infants, 21,703 (2.9%) received intravenous antibiotics. The number of infants classified as CN ≥ 5d, CN < 5d, and CP-EOS was 7996 (37%), 13,330 (61%), and 375 (1.7%). The incidence of CN ≥ 5d, CN < 5d, and CP-EOS was 10.6 (95% CI 10.3–10.8), 17.6 (95% CI 17.3–17.9), and 0.49 (95% CI 0.44–0.54) cases per 1000 livebirths. The median (IQR) number of antibiotic days administered for CN ≥ 5d, CN < 5d, and CP-EOS was 77 (77–78), 53 (52–53), and 5 (5-5) per 1000 livebirths.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>CN ≥ 5d substantially contributed to the overall antibiotic exposure, and was 21-fold more frequent than CP-EOS. Antimicrobial stewardship programs should focus on shortening antibiotic treatment for culture-negative cases.</p><h3 data-test=\"abstract-sub-heading\">Impact</h3><ul>\n<li>\n<p>In a study of 757,979 infants born in high-income countries, we report a presumed culture-negative early-onset sepsis incidence of 10.6/1000 livebirths with an associated antibiotic exposure of 77 antibiotic days per 1000 livebirths.</p>\n</li>\n<li>\n<p>This study sheds light on the major contribution of presumed culture-negative early-onset sepsis to early-life antibiotic exposure.</p>\n</li>\n<li>\n<p>Given the diagnostic uncertainty surrounding culture-negative early-onset sepsis, the low mortality rate, and the disproportionate antibiotic exposure associated with this condition, our study emphasizes the importance of targeting culture-negative early-onset sepsis in antimicrobial stewardship programs.</p>\n</li>\n</ul>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41390-024-03532-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed the contribution of culture-negative cases to the overall antibiotic exposure in the first postnatal week.
Methods
We conducted a retrospective analysis across eleven countries in Europe, North America, and Australia. All late-preterm and term infants born between 2014 and 2018 who received intravenous antibiotics during the first postnatal week were classified as culture-negative cases treated for ≥5 days (CN ≥ 5d), culture-negative cases treated for <5 days (CN < 5d), or CP-EOS cases.
Results
Out of 757,979 infants, 21,703 (2.9%) received intravenous antibiotics. The number of infants classified as CN ≥ 5d, CN < 5d, and CP-EOS was 7996 (37%), 13,330 (61%), and 375 (1.7%). The incidence of CN ≥ 5d, CN < 5d, and CP-EOS was 10.6 (95% CI 10.3–10.8), 17.6 (95% CI 17.3–17.9), and 0.49 (95% CI 0.44–0.54) cases per 1000 livebirths. The median (IQR) number of antibiotic days administered for CN ≥ 5d, CN < 5d, and CP-EOS was 77 (77–78), 53 (52–53), and 5 (5-5) per 1000 livebirths.
Conclusions
CN ≥ 5d substantially contributed to the overall antibiotic exposure, and was 21-fold more frequent than CP-EOS. Antimicrobial stewardship programs should focus on shortening antibiotic treatment for culture-negative cases.
Impact
In a study of 757,979 infants born in high-income countries, we report a presumed culture-negative early-onset sepsis incidence of 10.6/1000 livebirths with an associated antibiotic exposure of 77 antibiotic days per 1000 livebirths.
This study sheds light on the major contribution of presumed culture-negative early-onset sepsis to early-life antibiotic exposure.
Given the diagnostic uncertainty surrounding culture-negative early-onset sepsis, the low mortality rate, and the disproportionate antibiotic exposure associated with this condition, our study emphasizes the importance of targeting culture-negative early-onset sepsis in antimicrobial stewardship programs.
期刊介绍:
Pediatric Research publishes original papers, invited reviews, and commentaries on the etiologies of children''s diseases and
disorders of development, extending from molecular biology to epidemiology. Use of model organisms and in vitro techniques
relevant to developmental biology and medicine are acceptable, as are translational human studies