Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections.

Autor:	Birgy A; Université de Paris, IAME, INSERM, F-75018 Paris, France.; AP-HP, Hôpital Robert Debré, Service de Microbiologie, F-75019 Paris, France., Madhi F; Service de Pédiatrie Générale, Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France.; Groupe de Pathologie Infectieuse Pédiatrique (GPIP), Paris, France.; Université Paris Est, IMRB-GRC GEMINI, 94000 Créteil, ACTIV France., Jung C; Service de Pédiatrie Générale, Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France.; Centre de Recherche Clinique, Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France., Levy C; Groupe de Pathologie Infectieuse Pédiatrique (GPIP), Paris, France.; Centre de Recherche Clinique, Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France.; Association Clinique Thérapeutique Infantile du Val de Marne (ACTIV), Saint Maur des Fossés, France., Cointe A; Université de Paris, IAME, INSERM, F-75018 Paris, France.; AP-HP, Hôpital Robert Debré, Service de Microbiologie, F-75019 Paris, France., Bidet P; Université de Paris, IAME, INSERM, F-75018 Paris, France.; AP-HP, Hôpital Robert Debré, Service de Microbiologie, F-75019 Paris, France., Hobson CA; Université de Paris, IAME, INSERM, F-75018 Paris, France., Bechet S; Association Clinique Thérapeutique Infantile du Val de Marne (ACTIV), Saint Maur des Fossés, France., Sobral E; Association Clinique Thérapeutique Infantile du Val de Marne (ACTIV), Saint Maur des Fossés, France., Vuthien H; AP-HP, HU-Est Parisien site Trousseau, Service de Bactériologie, F-75012 Paris, France., Ferroni A; AP-HP, Hopital Necker, Service de Microbiologie, University Paris Descartes, Paris, France., Aberrane S; Microbiology Laboratory, Créteil Hospital, 94000 Créteil, France., Cuzon G; Bacteriology-Hygiene Unit, Assistance Publique/Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France.; Université Paris Sud, LabEx LERMIT, Faculty of Medicine, Le Kremlin-Bicêtre, France.; Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-producing Enterobacteriaceae, Le Kremlin-Bicêtre, France.; Evolution and Ecology of Resistance to Antibiotics Unit, Institut Pasteur, APHP-Université Paris Sud, Paris, France., Beraud L; Centre National de Référence des Légionelles, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France., Gajdos V; Service de Pédiatrie, Antoine Béclère University Hospital, Assistance Publique-Hôpitaux de Paris, Clamart, France.; Centre for Research in Epidemiology and Population Health, Villejuif, France., Launay E; Service de Pédiatrie Générale et Infectiologie Pédiatrique, Hôpital Femme-Enfant-Adolescent, Centre Hospitalier Universitaire de Nantes, Nantes, France., Pinquier D; Unité de Pneumologie et Allergologie pédiatriques & CRCM mixte, Pédiatrie Médicale, CHU Charles Nicolle, Rouen, France., Haas H; Hôpitaux pédiatriques CHU Lenval, Nice, France., Desmarest M; Service d'Accueil des Urgences Pédiatriques, AP-HP, Hôpital Robert Debré, Paris, France., Dommergues MA; Groupe de Pathologie Infectieuse Pédiatrique (GPIP), Paris, France.; Service de pédiatrie, centre hospitalier de Versailles, Le Chesnay, France., Cohen R; Groupe de Pathologie Infectieuse Pédiatrique (GPIP), Paris, France.; Université Paris Est, IMRB-GRC GEMINI, 94000 Créteil, ACTIV France.; Centre de Recherche Clinique, Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France.; Association Clinique Thérapeutique Infantile du Val de Marne (ACTIV), Saint Maur des Fossés, France.; Unité Court Séjour, Petits Nourrisson, Service de Néonatologie, Centre Hospitalier Intercommunal de Créteil, 94000 Créteil France., Bonacorsi S; Université de Paris, IAME, INSERM, F-75018 Paris, France.; AP-HP, Hôpital Robert Debré, Service de Microbiologie, F-75019 Paris, France.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2021 Oct 11; Vol. 76 (11), pp. 2839-2846.
DOI:	10.1093/jac/dkab289
Abstrakt:	Objectives: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of β-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. Materials and Methods: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of β-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. Results: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant β-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). Conclusions: Despite the frequent association of ESBL genes with inhibitor-resistant β-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children. (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu