Azole-resistant Aspergillus fumigatus with the environmental TR46/Y121F/T289A mutation in India

Abstract

Triazole antifungals are the mainstay of therapy for patients with aspergillosis. Notably, the mortality associated with aspergillosis is high and the rate of treatment failure is much higher if patients are infected with multiple-triazole-resistant (MTR) Aspergillus fumigatus.1,2 MTR A. fumigatus strains with the mutation TR34/L98H occur both in azole-treated as well as in azole-naive patients and have increasingly been reported from Dutch patients and their environment and from other European and Asian countries.1–7 Molecular studies from Europe and India suggested that use of azole fungicides in the environment selects MTR A. fumigatus TR34/L98H strains.7,8 This issue is further complicated by the emergence of a new resistance mechanism, TR46/Y121F/T289A in the cyp51A gene responsible for voriconazole resistance in A. fumigatus, which was detected in 2009 in a Dutch patient and has been recently reported in series of patients from the Netherlands.9,10 We report the occurrence of the same TR46/Y121F/T289A mutations in environmental A. fumigatus strains in India, which were also cross-resistant to commonly used azole fungicides.