The Global Antifungal Susceptibility Epidemiology of Trichophyton indotineae Indicating Voriconazole as an Alternative Therapy for Recalcitrant Dermatophytosis

Abstract

Background: The emergence of Trichophyton indotineae as a multidrug-resistant dermatophyte has challenged conventional therapeutic approaches for dermatophytosis, leading to a significant therapeutic dilemma. The absence of formal epidemiological cutoff values (ECVs) under the Clinical and Laboratory Standards Institute (CLSI) framework has led to inconsistent interpretation of antifungal susceptibility testing (AFST) data, highlighting the urgent need for standardised susceptibility interpretation criteria and effective therapeutic strategies. Objectives: This study aimed to (1) establish CLSI-based estimated tentative ECVs (ET-ECVs) to facilitate reliable minimum inhibitory concentration (MIC) interpretation; (2) analyse resistance rates of T. indotineae to terbinafine, itraconazole and voriconazole using a large-scale global dataset and (3) explore and identify effective therapeutic options following first-line treatment failure. Methods: This systematic review compiled global susceptibility data for T. indotineae through comprehensive literature searches, including only studies that performed CLSI- or European Committee on Antimicrobial Susceptibility Testing (EUCAST)-standardised AFST. Furthermore, the clinical efficacy of voriconazole was specifically evaluated by summarising and analysing reported treatment cases. Results: A total of 67 studies from 14 countries, comprising 981 isolates, were included. The proposed CLSI ET-ECVs for terbinafine, itraconazole and voriconazole were 0.125, 0.25 and 1 mg/L, respectively, showing full alignment with EUCAST tentative epidemiological cutoff values (TECOFFs). Integrated resistance rates were 77.6% for terbinafine, 17.0% for itraconazole and 1.4% for voriconazole. Cross-resistance analysis revealed that terbinafine resistance predominated, with 14.3% of isolates co-resistant to itraconazole. In vitro susceptibility data demonstrated high activity of voriconazole and clinical case summaries further confirmed its favourable therapeutic efficacy, with complete remission reported in all evaluated cases. Conclusion: This study defined the CLSI ET-ECVs for interpreting T. indotineae MICs, highlighted the resistance burden to first-line agents and provided in vitro evidence supporting further evaluation of voriconazole as a potential effective alternative therapy. These findings may provide critical warnings regarding the high-resistance landscape and help guide antifungal susceptibility interpretation for this emerging multidrug-resistant pathogen.