Clinical and Mycological Profiles of Chronic and Recalcitrant Dermatophytosis: Türkiye, 2022-2024

This study investigated the treatment outcomes of 91 patients with chronic and recalcitrant dermatophytosis from 20 hospitals in Türkiye between June 2022 and March 2024, as well as the in vitro antifungal susceptibility and squalene epoxidase (SQLE) substitution profiles of the dermatophytes obtained from these patients. Molecular identification by sequencing 91 isolates, revealed 76 Trichophyton mentagrophytes ITS genotype VIII (TmVIII; also known as T. indotineae) isolates, 13 Trichophyton rubrum, one Trichophyton tonsurans, and one Microsporum canis. The Phe397Leu substitution predominated in the SQLE, and Tyr414His co-occurred in nine TmVIII isolates. Five novel substitutions were observed in TmVIII. Among 13 T. rubrum isolates, three showed different SQLE substitution patterns compared to the wild-type strain. EUCAST antifungal susceptibility testing revealed high minimum inhibitory concentrations (MICs) for terbinafine (TRB) (> 0.25 mg/L) and for fluconazole (FLZ) (≥ 16 mg/L), indicating resistance in most TmVIII isolates. Of the 91 patients, 83 responded to FLZ, itraconazole (ITZ), TRB, or voriconazole-based regimens. While adjunct therapy with FLZ and resveratrol (RES) led to improvement in 28/29 patients despite their high in vitro inhibition concentrations, ITZ and curcumin (CUR) therapy was successful in 3/3 patients. However, the in vitro efficiency of CUR could not be evaluated. These findings highlight the local occurrence of specific SQLE substitutions, underscore the importance of EUCAST MIC testing combined with SQLE sequencing for surveillance, and support further evaluation of RES and CUR as an adjunct in TRB-resistant TmVIII.