First Reported Cases of Terbinafine-Resistant Trichophyton indotineae Isolates in Israel: Epidemiology, Clinical Characteristics and Response to Treatment

Abstract

Background: Trichophyton indotineae, a newly defined species within the T. mentagrophytes/T. interdigitale complex, has emerged as an epidemiological concern worldwide. However, owing to the limitations of commonly applied fungal identification techniques, T. indotineae remains underreported. In addition, T. indotineae's response to treatment has been described in only a few studies.

Objective: To investigate the prevalence, clinical characteristics and treatment outcomes of terbinafine-resistant T. mentagrophytes/T. interdigitale complex infections, as well as to detect T. indotineae cases.

Patients and methods: A retrospective cohort study was conducted on 22 patients with T. mentagrophytes/T. interdigitale complex infections between 2019 and 2023, using either culture or commercial polymerase chain reaction methods. Patient demographics, disease characteristics and treatment responses were recorded. Patients non-responsive to oral terbinafine underwent further analyses, including DNA sequencing of the internal transcribed spacer region for accurate species identification and mutational analysis of the squalene epoxidase (SQLE) gene.

Results: The mean age of the patients was 49.7 years (±18.2), with 54.5% men. Terbinafine-resistant T. mentagrophytes/T. interdigitale complex infections were reported in 46.2% of the cohort (n = 6/13 patients; 9 lost to treatment response follow-up), all of whom exhibited extensive dermatophytosis. Among the terbinafine-resistant T. mentagrophytes/T. interdigitale isolates, all five isolates available for fungal analysis were identified as T. indotineae, harbouring SQLE single-point mutations (Phe397Leu and Leu393Ser). Only three of the terbinafine-resistant cases responded to oral itraconazole 200 mg/day, with two responding only to oral voriconazole and one to oral itraconazole 400 mg/day.

Conclusion: All cases of T. mentagrophytes/T. interdigitale assessed in this study were identified as T. indotineae, which exhibits SQLE gene mutations. This underscores the importance of integrating methods to detect T. indotineae in routine clinical practice.

Keywords: Trichophyton indotineae; Trichophyton mentagrophytes/Trichophyton interdigitale complex; antifungal treatment; dermatophyte; tinea corporis; treatment efficacy.