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Alarming India‐wide phenomenon of antifungal resistance in dermatophytes: A multicentre study
Author(s) -
Ebert Andreas,
Monod Michel,
Salamin Karine,
Burmester Anke,
Uhrlaß Silke,
Wiegand Cornelia,
Hipler UtaChristina,
Krüger Constanze,
Koch Daniela,
Wittig Franziska,
Verma Shyam B.,
Singal Archana,
Gupta Sanjeev,
Vasani Resham,
Saraswat Abir,
Madhu Rengarajan,
Panda Saumya,
Das Anupam,
Kura Mahendra M.,
Kumar Akshy,
Poojary Shital,
Schirm Sibylle,
Gräser Yvonne,
Paasch Uwe,
Nenoff Pietro
Publication year - 2020
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.13091
Subject(s) - terbinafine , squalene monooxygenase , voriconazole , itraconazole , dermatophyte , trichophyton , trichophyton rubrum , biology , posaconazole , internal transcribed spacer , microbiology and biotechnology , drug resistance , antifungal , genetics , gene , ribosomal rna , biosynthesis
Background An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario. Objectives The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase ( SQLE ) gene. Patients/Methods We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE . Results Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine‐sensitive and terbinafine‐resistant isolates but was associated with increased MICs of itraconazole and voriconazole. Conclusions The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.