Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR/L98H mutations in the cyp51A gene in India

Anuradha Chowdhary*, Shallu Kathuria, Harbans S Randhawa, Shailendra N Gaur, Corné H Klaassen, Jacques F Meis

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

168 Citations (Scopus)

Abstract

OBJECTIVES: 

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.

METHODS: 

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.

RESULTS: 

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.

CONCLUSIONS:

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.

Original languageEnglish
Pages (from-to)362-366
Number of pages5
JournalThe Journal of antimicrobial chemotherapy
Volume67
Issue number2
DOIs
Publication statusPublished - Feb 2012
Externally publishedYes

Bibliographical note

Funding:
This work was partly supported by the Indian Council of Medical Research,
New Delhi (HIV/50/107/2008). Part of this work was done during a
research fellowship of A. C. at the Canisius Wilhelmina Hospital,
Nijmegen, The Netherlands, which was sponsored by Labland BV,
Wijchen, The Netherlands.

Fingerprint

Dive into the research topics of 'Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR/L98H mutations in the cyp51A gene in India'. Together they form a unique fingerprint.

Cite this