{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:11:08Z","timestamp":1781737868575,"version":"3.54.5"},"reference-count":28,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["67821661"],"award-info":[{"award-number":["67821661"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ACTIV","award":["67821661"],"award-info":[{"award-number":["67821661"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Haemophilus influenzae (Hi) is one of the leading bacteria implicated in childhood acute otitis media (AOM). Recent concerns have been raised about the emergence of Hi-resistant strains. We aimed to analyze the evolution of \u03b2-lactam resistance to Hi among strains isolated from nasopharyngeal carriage in children with AOM and in mild ear fluid (MEF) after the spontaneous perforation of the tympanic membrane (SPTM) in France. In this national ambulatory-based cohort study over 16 years, we analyzed the rate of Hi nasopharyngeal carriage and the proportion of \u03b2-lactam-resistant Hi strains over time using a segmented linear regression model. Among the 13,865 children (median [IQR] age, 12.7 [9.3\u201317.3] months; 7400 [53.4%] male) with AOM included from November 2006 to July 2022, Hi was isolated in 7311 (52.7%) children by nasopharyngeal sampling. The proportion of \u03b2-lactamase-producing and \u03b2-lactamase-negative, ampicillin-resistant (BLNAR) Hi strains in nasopharyngeal carriage remained stable during the study period. Among the 783 children (median [IQR] age, 20 [12.3\u201337.8] months; 409 [52.2%] male) with SPTM included from October 2015 to July 2022, Hi was isolated in 177 (22.6%) cases by MEF sampling. The proportions of \u03b2-lactamase-producing and BLNAR Hi strains did not significantly differ between nasopharyngeal (17.6% and 8.8%, respectively) and MEF (12.6% and 7.4%) samples. Accordingly, amoxicillin remains a valid recommendation as the first-line drug for AOM in France.<\/jats:p>","DOI":"10.3390\/antibiotics12111605","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T07:02:05Z","timestamp":1699426925000},"page":"1605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antibiotic Resistance of Haemophilus influenzae in Nasopharyngeal Carriage of Children with Acute Otitis Media and in Middle Ear Fluid from Otorrhea"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6168-1351","authenticated-orcid":false,"given":"Zein","family":"Assad","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Pediatric Infectious Disease and Internal Medicine, Robert Debr\u00e9 University Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75019 Paris, France"},{"name":"Infection, Antimicrobials, Modelling, Evolution (IAME), Inserm UMR 1137, Paris Cit\u00e9 University, 75018 Paris, France"},{"name":"Groupe de Pathologie Infectieuse P\u00e9diatrique (GPIP), 06200 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6151-0686","authenticated-orcid":false,"given":"Robert","family":"Cohen","sequence":"additional","affiliation":[{"name":"Groupe de Pathologie Infectieuse P\u00e9diatrique (GPIP), 06200 Nice, France"},{"name":"Association Clinique et Th\u00e9rapeutique Infantile du Val-de-Marne (ACTIV), 94000 Cr\u00e9teil, France"},{"name":"Institut Mondor de Recherche Biom\u00e9dicale-Groupe de Recherche Clinique Groupe d\u2019Etude des Maladies Infectieuses N\u00e9onatales et Infantiles (IMRB-GRC GEMINI), Universit\u00e9 Paris Est, 94000 Cr\u00e9teil, France"},{"name":"Association Fran\u00e7aise de P\u00e9diatrie Ambulatoire (AFPA), 45000 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-2838","authenticated-orcid":false,"given":"Emmanuelle","family":"Varon","sequence":"additional","affiliation":[{"name":"National Reference Center for Pneumococci, Centre de Recherche Clinique et Biologique, Centre Hospitalier Intercommunal de Cr\u00e9teil, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1927-6360","authenticated-orcid":false,"given":"Corinne","family":"Levy","sequence":"additional","affiliation":[{"name":"Groupe de Pathologie Infectieuse P\u00e9diatrique (GPIP), 06200 Nice, France"},{"name":"Association Clinique et Th\u00e9rapeutique Infantile du Val-de-Marne (ACTIV), 94000 Cr\u00e9teil, France"},{"name":"Institut Mondor de Recherche Biom\u00e9dicale-Groupe de Recherche Clinique Groupe d\u2019Etude des Maladies Infectieuses N\u00e9onatales et Infantiles (IMRB-GRC GEMINI), Universit\u00e9 Paris Est, 94000 Cr\u00e9teil, France"},{"name":"Association Fran\u00e7aise de P\u00e9diatrie Ambulatoire (AFPA), 45000 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Bechet","sequence":"additional","affiliation":[{"name":"Association Clinique et Th\u00e9rapeutique Infantile du Val-de-Marne (ACTIV), 94000 Cr\u00e9teil, France"},{"name":"Association Fran\u00e7aise de P\u00e9diatrie Ambulatoire (AFPA), 45000 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Corrard","sequence":"additional","affiliation":[{"name":"Association Clinique et Th\u00e9rapeutique Infantile du Val-de-Marne (ACTIV), 94000 Cr\u00e9teil, France"},{"name":"Association Fran\u00e7aise de P\u00e9diatrie Ambulatoire (AFPA), 45000 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Werner","sequence":"additional","affiliation":[{"name":"Groupe de Pathologie Infectieuse P\u00e9diatrique (GPIP), 06200 Nice, France"},{"name":"Association Clinique et Th\u00e9rapeutique Infantile du Val-de-Marne (ACTIV), 94000 Cr\u00e9teil, France"},{"name":"Association Fran\u00e7aise de P\u00e9diatrie Ambulatoire (AFPA), 45000 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na\u00efm","family":"Ouldali","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Pediatric Infectious Disease and Internal Medicine, Robert Debr\u00e9 University Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75019 Paris, France"},{"name":"Infection, Antimicrobials, Modelling, Evolution (IAME), Inserm UMR 1137, Paris Cit\u00e9 University, 75018 Paris, France"},{"name":"Groupe de Pathologie Infectieuse P\u00e9diatrique (GPIP), 06200 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Bonacorsi","sequence":"additional","affiliation":[{"name":"Infection, Antimicrobials, Modelling, Evolution (IAME), Inserm UMR 1137, Paris Cit\u00e9 University, 75018 Paris, France"},{"name":"Department of Microbiology, Robert Debr\u00e9 University Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2898-3710","authenticated-orcid":false,"given":"Alexis","family":"Rybak","sequence":"additional","affiliation":[{"name":"Groupe de Pathologie Infectieuse P\u00e9diatrique (GPIP), 06200 Nice, France"},{"name":"Association Clinique et Th\u00e9rapeutique Infantile du Val-de-Marne (ACTIV), 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sabuncu, E., David, J., Bern\u00e8de-Bauduin, C., P\u00e9pin, S., Leroy, M., Bo\u00eblle, P.-Y., Watier, L., and Guillemot, D. 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