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: | Emilie Sacchetto, Alain Haloun, Guillaume Ghislain Aubin, Patrice Le Pape, Dea Garcia-Hermoso, Isabelle Danner-Boucher, Florent Morio, Michel Miegeville, Stéphane Bretagne |
| المساهمون: | Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This study was supported by internal funding., 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Journal of Antimicrobial Chemotherapy Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2012, 67 (8), pp.1870-1873. ⟨10.1093/jac/dks160⟩ Journal of Antimicrobial Chemotherapy, 2012, 67 (8), pp.1870-1873. ⟨10.1093/jac/dks160⟩ |
| بيانات النشر: | Oxford University Press (OUP), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, MESH: Sequence Analysis, DNA, Posaconazole, Antifungal Agents, Cystic Fibrosis, MESH: Tubulin, Cystic fibrosis, Aspergillus fumigatus, Tubulin, MESH: Child, Prevalence, Agar, Pharmacology (medical), CFTR, Child, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Microbial Sensitivity Tests, 0303 health sciences, multi-azole resistance, MESH: Middle Aged, biology, cyp51A mutations, MESH: Voriconazole, Middle Aged, 3. Good health, Infectious Diseases, MESH: Young Adult, Child, Preschool, France, Itraconazole, MESH: Aspergillus fumigatus, medicine.drug, Adult, Microbiology (medical), food.ingredient, Adolescent, MESH: Cystic Fibrosis, Microbial Sensitivity Tests, In Vitro Techniques, A. fumigatus, MESH: Drug Resistance, Fungal, Microbiology, Agar plate, Young Adult, 03 medical and health sciences, food, Drug Resistance, Fungal, medicine, Aspergillosis, Humans, MESH: Aspergillosis, Gene, MESH: Prevalence, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, MESH: In Vitro Techniques, Pharmacology, Voriconazole, MESH: Humans, 030306 microbiology, MESH: Child, Preschool, MESH: Adult, MESH: Retrospective Studies, Sequence Analysis, DNA, Triazoles, MESH: Antifungal Agents, medicine.disease, biology.organism_classification, MESH: Male, MESH: France, Pyrimidines, MESH: Triazoles, MESH: Pyrimidines, MESH: Itraconazole |
| 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. |
| تدمد: | 1460-2091 0305-7453 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7427f76faab04628ac2be47a72fa63cfTest https://doi.org/10.1093/jac/dks160Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7427f76faab04628ac2be47a72fa63cf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602091 03057453 |
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