دورية أكاديمية
High prevalence of triazole resistance in Aspergillus fumigatus, especially mediated by TR/L98H, in a French cohort of patients with cystic fibrosis
| العنوان: | High prevalence of triazole resistance in Aspergillus fumigatus, especially mediated by TR/L98H, in a French cohort of patients with cystic fibrosis |
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| المؤلفون: | Morio, Florent, Aubin, Guillaume, Ghislain, Danner-Boucher, Isabelle, Haloun, Alain, Sacchetto, Emilie, Garcia-Hermoso, Dea, Bretagne, Stéphane, Miegeville, Michel, Le Pape, Patrice |
| المساهمون: | Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS), This study was supported by internal funding. |
| المصدر: | ISSN: 0305-7453. |
| بيانات النشر: | HAL CCSD Oxford University Press (OUP) |
| سنة النشر: | 2012 |
| المجموعة: | Université de Nantes: HAL-UNIV-NANTES |
| مصطلحات موضوعية: | CFTR, A. fumigatus, cyp51A mutations, multi-azole resistance, MESH: Adolescent, MESH: Adult, MESH: Aspergillus fumigatus, MESH: Child, MESH: Humans, Preschool, MESH: Cystic Fibrosis, MESH: Drug Resistance, Fungal, MESH: France, MESH: In Vitro Techniques, MESH: Itraconazole, MESH: Male, MESH: Retrospective Studies, MESH: Microbial Sensitivity Tests, MESH: Middle Aged, MESH: Prevalence, MESH: Pyrimidines, MESH: Sequence Analysis, DNA, MESH: Antifungal Agents, MESH: Triazoles, MESH: Tubulin, MESH: Voriconazole, MESH: Young Adult, MESH: Aspergillosis |
| الوصف: | Part of this work has been presented at the Fifth Congress on Trends in Medical Mycology, Valencia, Spain, 2011 (Abstract no. 308) ; International audience ; OBJECTIVES:Triazole resistance in Aspergillus fumigatus due to a single azole resistance mechanism (TR/L98H) is increasingly reported in European countries. Data from patients with cystic fibrosis (CF) are limited. Our study aimed to investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus in a cohort of patients with CF.METHODS:Eighty-five A. fumigatus isolates from 50 CF patients, collected between January 2010 and April 2011, were retrospectively analysed for azole resistance using agar plates containing 4 mg/L itraconazole. MICs of itraconazole, voriconazole and posaconazole were determined according to EUCAST methodology for each isolate able to grow on this medium. Species identification was performed by sequencing of the β-tubulin gene. Sequencing analysis of the cyp51A gene and its promoter region was conducted.RESULTS:Nine isolates (four patients, 8% prevalence) were able to grow on itraconazole-containing agar plates. Itraconazole resistance was confirmed by EUCAST methodology (MICs >2 mg/L). All isolates had mutations in the cyp51A gene at residues previously involved in azole resistance: L98H (n = 5), M220T (n = 4) and G54R (n = 1). One patient had three genetically distinct azole-resistant isolates identified during the study. The isolates with L98H that were recovered from three patients (6% prevalence) also had the 34 bp tandem repeat in the promoter region of cyp51A (TR/L98H) and displayed multiazole resistance.CONCLUSIONS:We report an 8% prevalence of itraconazole resistance in CF patients in our centre, mostly driven by TR/L98H (6%). Our data confirm that TR/L98H occurs in France and can be highly prevalent in CF patients. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/22581906; pasteur-02262445; https://pasteur.hal.science/pasteur-02262445Test; PUBMED: 22581906 |
| DOI: | 10.1093/jac/dks160 |
| الإتاحة: | https://doi.org/10.1093/jac/dks160Test https://pasteur.hal.science/pasteur-02262445Test |
| رقم الانضمام: | edsbas.68710999 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/jac/dks160 |
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