[Trichophyton mentagrophytes ITS genotype VIII/Trichophyton indotineae in Germany-revisit after 5 years]

Trichophyton (T.) mentagrophytes ITS genotype VIII/T. indotineae (TMVIII/TINDO) is a new, anthropophilic dermatophyte from the T. mentagrophytes/T. interdigitale complex that has gained increasing importance worldwide in recent years. This pathogen is characterized by frequent terbinafine resistance and a clinical picture of pronounced, inflammatory, and therapy-resistant dermatophytoses that predominantly affect the groin, trunk, extremities, and face. Between 2018 and the end of 2024, all TMVIII/TINDO cases detected in patients from Germany by culture and/or molecular biology were systematically recorded at the Leipzig-Mölbis laboratory. Identification and genotyping were performed by sequencing the internal transcribed spacer (ITS) region of the rDNA. In vitro resistance testing for terbinafine and itraconazole was performed using a breakpoint test. Additionally, the squalene epoxidase (SQLE) gene was sequenced to analyze resistance-associated point mutations. A total of 242 isolates from 196 patients were identified; some patients were consecutively detected repeatedly. The majority of affected patients had a migration background, particularly from South Asia (especially India) and Arab countries. Only a few infections were diagnosed in patients of German descent. As part of the diagnostic workup an in vitro susceptibility testing was performed using a breakpoint test, which demonstrated terbinafine resistance in 61.8% of the TMVIII/TINDO strains. Point mutations in the SQLE gene that correlated with resistance were found in a total of 161 of 188 strains. The most frequently detected mutation was Phe³⁹⁷Leu, which was associated with terbinafine resistance and clinical treatment failure with terbinafine in all cases. In addition, double mutations were detected in 26 strains. In vitro itraconazole resistance was observed in 11 of 186 tested isolates, corresponding to 5.9%. Itraconazole is currently the drug of choice for the systemic treatment of TMVIII/TINDO dermatophytoses. The recommended dosage is 100 mg twice daily for a period of 4-8 weeks, or up to 12 weeks if needed. Concurrent topical treatment with azoles, amorolfine, or ciclopirox is always recommended. In the event of itraconazole treatment failure, there are currently no standardized treatment recommendations. The off-label use of voriconazole has been reported in isolated cases, and there is also experimental experience with other active ingredients. The spread of TMVIII/TINDO in Germany and worldwide is particularly worrying in view of the dermatophyte's resistance to terbinafine and itraconazole.