Drug Sensitivity Profile of Fungi Isolated from Onychomycosis Patients and Evaluation of Squalene Epoxidase Mutation in One Terbinafine-Resistant Trichophyton mentagrophytes Species.

Abstract

Background: The resistance to treatment of onychomycosis is increasingly reported. The present study aimed to assess the antifungal activity of itraconazole, terbinafine, luliconazole, and efinaconazole against dermatophytes, molds, and also yeast isolated from patients with onychomycosis. Furthermore, the mechanism of resistance to terbinafine in resistant Trichophyton mentagrophytes species was evaluated using the squalene epoxidase (SQLE) gene sequence. Methods: A total of 71 fungal isolates were collected from 97 patients with suspected onychomycosis. The identification of fungal species was performed using conventional and molecular approaches. In vitro drug susceptibility for itraconazole, terbinafine, luliconazole, and efinaconazole was carried out using the broth microdilution method according to the CLSI-M60 and CLSI-M38 3rd ed., respectively. The SQLE gene of one terbinafine-resistant T. mentagrophytes was amplified using the specific primers. Results: Efinaconazole and luliconazole demonstrated higher effectiveness against all isolates in the study. One mismatch was detected at position 1177, which showed A → C change associated with Phe397Leu amino acid substitution of the SQLE protein in terbinafine-resistant T. mentagrophytes. Conclusion: The occurrence of resistant strains of organisms causing onychomycosis should be considered and evaluated. Furthermore, the identification of amino acid changes responsible for resistance to antifungals is a useful consideration in drug-target interaction.