Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR34/L98H and TR46/Y121F/T289A mutations in the cyp51A gene from clinical and environmental sources in India

Ref ID: 19621

Author:

Cheshta Sharma1*. Shallu Kathuria1, Jacques F Meis2-3 and Anuradha Chowdhary1

Author address:

‘Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi -110 007;
department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen.The Netherlands;
department of MedicalMicrob

Full conference title:

Society for Indian Human and Animal Mycologists 2014

Date: 10 January 2014

Abstract:

Molecular studies of well-studied pan azole resistant Aspergillus, fumigatus carrying TR34/ L98H mutation from Europe and
India suggest that clinical azole resistant isolates originated from environmental or fungicide driven route of resistance
development. TR46/Y121F/T289A mutation in the cyp51A gene responsible for voriconazole resistance in Aspergillus
fumigatus, has been recently reported in patients and from their environment in the Netherlands. The present study reports the
occurrence of TR34/L98H and TR46/Y121F/T289A in A.fumigatus strains from clinical and environmental sources
respectively from India. Clinical and soil samples were investigated by inoculation on Sabouraud’s dextrose agar (SDA) and
A. fumigatus colonies were subcultured on itraconazole (ITC+) and voriconazole (VRC+) containing SDA plates.
Identification of ITC+ and VRC + A.fumigatus strains was confirmed by sequencing fi-tubulin and calmodulin. Azole resistant
A. fumigatus were subjected to mixed-format real-time PCR for detecting mutations and genotyped with microsatellite
analysis. In vitro activity for azoles and 10 azole fungicides were investigated using CLSI M3 8-A2 broth microdillution. Seven
A. fumigatus strains from 7 patients grew on VRC+ and ITC+ plates. Of 198 environmental A. fumigatus strains, 16 were
resistant, of which eight each (6.8%) grew on VRC+ and ITC+ plates. All of the clinical resistant A.fumigatus isolates had high
MIC values of itraconazole (>16 mg/L), voriconazole (2 mg/L), posaconazole (2 mg/L) and isavuconazole (8 mg/L) and
exhibited TR34/L98H mutation. The GM MICs of 8 VRC+A fumigatus isolates showed reduced susceptibility of
voriconazole (10.07 mg/L) and isavuconazole (8 mg/L). These isolates exhibited TR46/Y121F/T289Amutation. All resistant
isolates showed cross-resistance to all fungicides tested. Isolation of azole resistant TR34/L98H and TR46/Y121F/T289A A.
fumigatus from India is worrisome and has implications in management of aspergillosis.
9830;Corresponding author
E-mail:cheshta03sharma@gmail.com

Abstract Number: OP-002

Conference Year: 2014

Link to conference website: http://www.siham2014.com

New link: NULL

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