Department of Medical Mycology, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China.
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, 210042, China.
Mycopathologia. 2023 Aug;188(4):383-393. doi: 10.1007/s11046-023-00761-x. Epub 2023 Jun 19.
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.
This study aimed to report the terbinafine- and itraconazole-resistant T. indotineae in Chinese mainland, by identifying the phylogenetic classification of the isolate strain, and detecting the drug resistance, gene mutation and expression.
PATIENTS/METHODS: The skin scales of the patient were cultured on SDA and the isolate was authenticated by DNA sequencing and MALDI-TOF MS. Antifungal susceptibility testing was performed following the M38-A2 CLSI protocol to examine the MICs values of terbinafine, itraconazole, fluconazole, etc. The strain was screened for mutations in the squalene epoxidase (SQLE) gene by Sanger sequencing and detected the expression of CYP51A and CYP51B by qRT-PCR.
A multi-resistant ITS genotype VIII sibling of the T. mentagrophytes complex (T. indotineae) was isolated in Chinese mainland. The strain harbored high terbinafine MIC of > 32 μg/mL and itraconazole MIC of 1.0 μg/mL, which was identified a mutation in the squalene epoxidase gene with amino acid substitution (PheLeu, 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.
The first domestic strain of terbinafine- and itraconazole-resistant T. indotineae from a patient in Chinese mainland was isolated. Itraconazole pulse therapy can be an effective method for the treatment of T. indotineae.
Trichophyton indotineae 是一种新的皮肤癣菌，由于在印度甚至全球范围内报告的特比萘芬耐药率较高，已成为治疗皮肤癣菌病的一个重要关注点。
本研究旨在通过鉴定分离株的系统发育分类，以及检测耐药性、基因突变和表达，报告中国大陆地区特比萘芬和伊曲康唑耐药的 T. indotineae。
患者/方法：患者的皮肤鳞屑在 SDA 上培养，通过 DNA 测序和 MALDI-TOF MS 鉴定分离株。采用 M38-A2 CLSI 方案进行抗真菌药敏试验，检测特比萘芬、伊曲康唑、氟康唑等 MIC 值。通过 Sanger 测序筛选 squalene epoxidase (SQLE) 基因突变，并通过 qRT-PCR 检测 CYP51A 和 CYP51B 的表达。
中国大陆地区分离出一株特比萘芬和伊曲康唑耐药的 T. mentagrophytes 复合体的多耐药 ITS 基因型 VIII 同胞种（T. indotineae）。该菌株对特比萘芬的 MIC 值高（>32 μg/mL），对伊曲康唑的 MIC 值为 1.0 μg/mL，这与 SQLE 基因突变（氨基酸取代 PheLeu，突变 1191C > A）有关。此外，还观察到 CYP51A 和 CYP51B 的过表达。由于多次复发，患者最终通过伊曲康唑脉冲治疗和外用克霉唑乳膏治疗 5 周后获得临床治愈。
从中国大陆地区的一位患者中分离出第一株特比萘芬和伊曲康唑耐药的 T. indotineae 国内菌株。伊曲康唑脉冲治疗可能是治疗 T. indotineae 的有效方法。
