Molecular Epidemiology and Antifungal Susceptibility of Trichophyton Isolates in Greece: Emergence of Terbinafine-Resistant Trichophytonmentagrophytes Type VIII Locally and Globally

Abstract

<i>Trichophyton</i> isolates with reduced susceptibility to antifungals are now increasingly reported worldwide. We therefore studied the molecular epidemiology and the in vitro antifungal susceptibility patterns of Greek <i>Trichophyton</i> isolates over the last 10 years with the newly released EUCAST reference method for dermatophytes. Literature was reviewed to assess the global burden of antifungal resistance in <i>Trichophyton</i> spp. The in vitro susceptibility of 112 <i>Trichophyton</i> spp. molecularly identified clinical isolates (70 <i>T. rubrum</i>, 24 <i>T. mentagrophytes</i>, 12 <i>T. interdigitale</i> and 6 <i>T. tonsurans)</i> was tested against terbinafine, itraconazole, voriconazole and amorolfine (EUCAST E.DEF 11.0). Isolates were genotyped based on the internal transcribed spacer (ITS) sequences and the target gene squalene epoxidase (SQLE) was sequenced for isolates with reduced susceptibility to terbinafine. All <i>T. rubrum, T. interdigitale</i> and <i>T. tonsurans</i> isolates were classified as wild-type (WT) to all antifungals, whereas 9/24 (37.5%) <i>T. mentagrophytes</i> strains displayed elevated terbinafine MICs (0.25-8 mg/L) but not to azoles and amorolfine. All <i>T. interdigitale</i> isolates belonged to ITS Type II, while <i>T. mentagrophytes</i> isolates belonged to ITS Type III* (<i>n</i> = 11), VIII (<i>n</i> = 9) and VII (<i>n</i> = 4). All non-WT <i>T. mentagrophytes</i> isolates belonged to Indian Genotype VIII and harbored Leu393Ser (<i>n</i> = 5) and Phe397Leu (<i>n</i> = 4) SQLE mutations. Terbinafine resistance rates ranged globally from 0-44% for <i>T. rubrum</i> and 0-76% for <i>T. interdigitale</i>/<i>T. mentagrophytes</i> with strong endemicity. High incidence (37.5%) of terbinafine non-WT <i>T. mentagrophytes</i> isolates (all belonging to ITS Type VIII) without cross-resistance to other antifungals was found for the first time in Greece. This finding must alarm for susceptibility testing of dermatophytes at a local scale particularly in non-responding dermatophytoses.