Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR/L98H mutations in the cyp51A gene in India
Open Access
- 25 October 2011
- journal article
- case report
- Published by Oxford University Press (OUP) in Journal of Antimicrobial Chemotherapy
- Vol. 67 (2), 362-366
- https://doi.org/10.1093/jac/dkr443
Abstract
Azole resistance in Aspergillus fumigatus isolates impacts on the management of aspergillosis since azoles are primary agents used for prophylaxis and therapy. We report the emergence of resistance to triazoles in two A. fumigatus isolates from patients in Delhi, India. One hundred and three A. fumigatus isolates, collected from 85 patients suspected of bronchopulmonary aspergillosis during 2005–10, were investigated for susceptibility to itraconazole, voriconazole, posaconazole and isavuconazole. We undertook a mixed-format real-time PCR assay for the detection of mutations leading to triazole resistance in A. fumigatus. The resistant isolates were compared with 25 Dutch TR/L98H-positive isolates by microsatellite analysis. Of the 103 A. fumigatus isolates tested, only 2 had high MIC values of itraconazole (>16 mg/L), voriconazole (2 mg/L), posaconazole (2 mg/L) and isavuconazole (8 mg/L). The resistant A. fumigatus isolates exhibited the TR/L98H genotype and showed identical patterns by microsatellite typing, but were different from 25 Dutch TR/L98H isolates. We report for the first time from India the occurrence of TR/L98H mutations in the cyp51A gene (responsible for reduced azole susceptibility) in two A. fumigatus isolates from patients with chronic respiratory disease who had not previously been exposed to azoles. The presence of TR/L98H is consistent with a route of resistance development through exposure to azole compounds in the environment. Given the emergence of azole resistance in environmental strains, continued surveillance of resistance in clinical A. fumigatus strains is desirable for successful therapy of aspergillosis.Keywords
This publication has 18 references indexed in Scilit:
- Environmental Study of Azole-Resistant Aspergillus fumigatus and Other Aspergilli in Austria, Denmark, and SpainAntimicrobial Agents and Chemotherapy, 2010
- Development of Azole Resistance in Aspergillus fumigatus during Azole Therapy Associated with Change in VirulencePLOS ONE, 2010
- Novel mixed-format real-time PCR assay to detect mutations conferring resistance to triazoles in Aspergillus fumigatus and prevalence of multi-triazole resistance among clinical isolates in the NetherlandsJournal of Antimicrobial Chemotherapy, 2010
- Frequency and Evolution of Azole Resistance inAspergillus fumigatusAssociated with Treatment Failure1Emerging Infectious Diseases, 2009
- Possible Environmental Origin of Resistance of Aspergillus fumigatus to Medical TriazolesApplied and Environmental Microbiology, 2009
- Emergence of Azole Resistance in Aspergillus fumigatus and Spread of a Single Resistance MechanismPLoS Medicine, 2008
- A New Aspergillus fumigatus Resistance Mechanism Conferring In Vitro Cross-Resistance to Azole Antifungals Involves a Combination of cyp51A AlterationsAntimicrobial Agents and Chemotherapy, 2007
- Multi-azole resistance in Aspergillus fumigatusInternational Journal of Antimicrobial Agents, 2006
- Use of a Novel Panel of Nine Short Tandem Repeats for Exact and High-Resolution Fingerprinting of Aspergillus fumigatus IsolatesJournal of Clinical Microbiology, 2005
- Correlation between in-vitro susceptibility testing to itraconazole and in-vivo outcome of Aspergillus fumigatus infectionJournal of Antimicrobial Chemotherapy, 1997