Antifungal drug susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates

Abstract

With regard to increasing number of antifungal-resistant dermatophytes, antifungal susceptibility testing of dermatophytes serves as a useful tool in managing clinical dermatophytosis. This study aimed to determine antifungal susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates. Based on our results, dermatophytosis was confirmed in 97 cases by direct microscopic examination, culture, and sequencing of ITS region. Antifungal susceptibility of 97 dermatophyte isolates distributed in four species including Trichophyton interdigitale (26 isolates), T. rubrum (19 isolates), T. tonsurans (29 isolates), and Epidermophyton floccosum (21 isolates) was assessed to nine antifungal agents using CLSI M38-A2 guidelines. Minimum inhibitory concentration range (MIC range) for luliconazole and terbinafine was 0.001-0.008 μg/ml and 0.003-> 32 μg/ml, compared to 0.03-64 μg/ml for griseofulvin, 0.01-16 μg/ml for itraconazole and voriconazole, 0.03-8 μg/ml for ketoconazole, 0.03-32 μg/ml for econazole, 0.03-1 μg/ml for lanoconazole, and 0.01-4 μg/ml for butenafine. Trichophyton tonsurans was the most susceptible (MIC = 0.006 μg/ml) and E. floccosum was the most resistant (MIC = 0.02 μg/ml) species to terbinafine. Terbinafine resistance was reported for two species, i.e., T. rubrum and T. tonsurans at the total rate of 2% which was due to Leu393Phe substitution in both species. Taken together, our results assist clinicians and prompt the current knowledge about the necessity of antifungal susceptibility testing to select effective strategies for management of clinical cases of dermatophytosis.

Keywords: Antifungal susceptibility testing; Dermatophytes; Dermatophytosis; Point mutation; Terbinafine resistance.