Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR/L98H mutations in the cyp51A gene in India.
OBJECTIVE
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.
Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. dranuradha@hotmail.com
Anuradha
A
Chowdhary
Shallu
S
Kathuria
Harbans S
HS
Randhawa
Shailendra N
SN
Gaur
Corné H
CH
Klaassen
Jacques F
JF
Meis
D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D016000:Cluster Analysis; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004271:DNA, Fungal / Q000235:genetics; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D020125:Mutation, Missense; D055732:Pulmonary Aspergillosis / Q000382:microbiology; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014230:Triazoles / Q000494:pharmacology*
D000935:Antifungal Agents; D004271:DNA, Fungal; D005656:Fungal Proteins; D014230:Triazoles; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus