Clinical Characteristics, Genomic Sequencing, and Treatment Response of 13 Cases Infected With the Emerging Pathogen, Trichopyhton indotineae, From Türkiye

Abstract

Background: Trichophyton indotineae is a global cause of dermatophytosis resistant to terbinafine and sometimes systemic azoles. We describe clinical features, treatment outcomes, and antifungal susceptibility in 13 DNA-confirmed cases. Methods: This retrospective study included 32 treatment cycles in 13 T. indotineae patients in Türkiye. Skin scrapings were cultured and identified by matrix-assisted laser desorption time of flight-mass spectrometry, with confirmation by internal transcribed spacer and the large subunit rRNA sequencing followed by phylogenetic analysis. Antifungal susceptibility testing and detection of squalene epoxidase (SQLE) gene mutations were performed using agar screening and EUCAST microdilution methods. Results: Thirteen immunocompetent patients (M/F: 7/6, mean age 40.3 ± 13.8 years) presented with widespread plaques. The median times to rash onset and diagnosis were 7 months and 8 months, respectively. Nine patients had previously failed standard-dose oral terbinafine. Among 32 antifungal treatment cycles (30 systemic, 2 topical) outcomes included 21 complete remissions (CR), 4 partial remissions (PR), 7 nonresponses, 3 adverse events, with 3 relapses, and 9 recurrences. By final follow-up, 12 patients achieved CR—with itraconazole, voriconazole, and fluconazole—while 1 had PR. Clinical responses to itraconazole and voriconazole generally aligned with the minimal inhibitory concentrations (MICs), whereas reactions to fluconazole did not. SQLE mutations were present in isolates with high terbinafine MICs but absent in those with low MICs. Discussion: CR was strongly associated with itraconazole, followed by voriconazole and fluconazole. Treatment outcomes didn't always match with MICs, suggesting prolonged treatment and nontraditional agents like voriconazole and posaconazole may be required. Clinicians should be vigilant in diagnosing and managing T. indotineae.