First isolation of the terbinafine- and itraconazole-resistant Trichophyton indotineae in China

Abstract Background Trichophyton indotineae , a new species of dermatophytes, has become a significant concern in treating dermatophytosis due to the high level of terbinafine resistance reported in India and even worldwide. Objectives We aimed to report the first case of the terbinafine- and itraconazole-resistant T. indotineae in China, by identifying the phylogenetic classification of the isolate strain, and detecting the drug resistance, gene mutation and expression. Patients/Methods: The skin scales of patient were cultured on SDA and authenticated by DNA sequencing and MALDI-TOF MS. Antifungal susceptibility to itraconazole,terbinafine et al was tested following the M38-A2 CLSI protocol to examine MIC. The isolate was screened for mutations in the squalene epoxidase ( SQLE ) gene by Sanger sequencing and detected the expression of CYP51A and CYP51B by qRT-PCR. Results We isolated the first multi-resistant ITS genotype VIII sibling of the T. mentagrophytes complex ( T. indotineae ) in China. The strain harbored high terbinafine MICs (>32 µg/mL) and had a mutation in the squalene epoxidase gene with amino acid substitution (Phe 397 Leu, mutation 1191C > A). In addition, overexpression of CYP51A and CYP51B was observed. With multiple relapses, the patient finally achieved clinical cure by itraconazole pulse therapy and topical clotrimazole cream for 5 weeks. Conclusions We reported the first indigenous case of T. indotineae in China, indicating the intensification of drug resistance in dermatophytes. Besides, we found longtime itraconazole pulse therapy (0.2g p. o. BID) may provide a practical reference for clinicians in treating refractory dermatophytes.