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High terbinafine resistance in Trichophyton interdigitale isolates in Delhi, India harbouring mutations in the squalene epoxidase gene
Author(s) -
Singh Ashutosh,
Masih Aradhana,
Khurana Ananta,
Singh Pradeep Kumar,
Gupta Meenakshi,
Hagen Ferry,
Meis Jacques F.,
Chowdhary Anuradha
Publication year - 2018
Publication title -
mycoses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 69
eISSN - 1439-0507
pISSN - 0933-7407
DOI - 10.1111/myc.12772
Subject(s) - terbinafine , squalene monooxygenase , dermatophyte , biology , trichophyton , trichophyton rubrum , microbiology and biotechnology , tinea capitis , internal transcribed spacer , drug resistance , gene , virology , genetics , antifungal , itraconazole , ribosomal rna , biosynthesis , horticulture
Summary In the last few years, infections caused by dermatophytes along with a concomitant increase in the number of difficult to treat cases have increasingly been recognised, indicating that dermatophytosis remains a challenging public health problem. The majority of infections are caused by Trichophyton rubrum and Trichophyton mentagrophytes complex. Terbinafine, an allylamine antifungal used orally and topically is considered to be a first‐line drug in the therapy of dermatophyte infections. Terbinafine resistance has been predominately attributed to point mutations in the squalene epoxidase ( SQLE ) target gene a key enzyme in the ergosterol biosynthetic pathway leading to single amino acid substitutions. Here, we report the largest series of 20 terbinafine‐resistant Trichophyton interdigitale isolates obtained predominately from cases of tinea corporis/cruris in three hospitals in Delhi, India exhibiting elevated MIC s (4 to ≥32 μg/mL) to terbinafine and all harbouring single‐point mutations Leu393Phe or Phe397Leu in the SQLE gene. In 12 (60%) T. interdigitale isolates, the Phe397Leu substitution was observed, whereas in the remaining 8 (40%) isolates the substitution Leu393Phe was reported for the first time in T. interdigitale . Furthermore, 10 susceptible T. interdigitale isolates (0.125‐2 μg/mL) had a wild‐type genotype. Remarkably, considerably high terbinafine resistance rate of 32% was observed among 63 T. interdigitale isolates identified by sequencing of the internal transcribed spacer region. This high level of terbinafine resistance of Indian dermatophyte isolates is worrisome warranting antifungal susceptibility testing and mutation analysis for monitoring this emerging resistance.