Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Mediprobe Research, London, Ontario, Canada.
Mediprobe Research, London, Ontario, Canada.
J Invest Dermatol. 2023 Dec;143(12):2476-2483.e7. doi: 10.1016/j.jid.2023.04.032. Epub 2023 May 24.
Resistance to oral terbinafine, the most commonly used antifungal to treat dermatophytosis and onychomycosis worldwide, is being increasingly reported. In this study, we aimed to investigate the species distribution and prevalence of squalene epoxidase mutations among toenail dermatophyte isolates. Samples from 15,683 patients suspected of onychomycosis visiting the offices of dermatologists and podiatrists in the United States were analyzed. Clinical information was reviewed, and dermatophyte species with or without squalene epoxidase mutations were detected using multiplex real-time PCRs. The frequency of dermatophytes was 37.6%; of isolates belonging to the Trichophyton genus, 88.3% were the T. rubrum complex, and 11.2% were the T. mentagrophytes complex. Individuals aged >70 years exhibited higher infection rates for the T. mentagrophytes complex. The overall mutation rate among Trichophyton spp. was 3.7%, with a higher mutation rate detected in the T. mentagrophytes complex (4.3 vs. 3.6%). Commonly detected mutations were T1189C/Phe397Leu (34.5%), T1306C/Phe415Ser (16.0%), and C1191A/Phe397Leu (11.0%). Squalene epoxidase gene mutations associated with decreased terbinafine susceptibility have been identified in United States patients with toenail onychomycosis. Physicians should be aware of the risk factors for resistance development and engage in antifungal stewardship practices such as directed diagnosis and treatment of dermatophytosis and onychomycosis.
抗口服特比萘芬的现象越来越多，特比萘芬是目前全球治疗皮肤癣菌病和甲真菌病最常用的抗真菌药物。本研究旨在调查趾甲皮肤癣菌分离株中角鲨烯环氧化酶突变的种分布和流行率。分析了美国皮肤科医生和足病医生办公室就诊的 15683 名疑似甲真菌病患者的样本。回顾了临床信息，并使用多重实时 PCR 检测了有或没有角鲨烯环氧化酶突变的皮肤癣菌。皮肤癣菌的频率为 37.6%；属于毛癣菌属的分离株中，88.3%为红色毛癣菌复合体，11.2%为须癣毛癣菌复合体。>70 岁的个体中，须癣毛癣菌复合体的感染率更高。毛癣菌属的总体突变率为 3.7%，须癣毛癣菌复合体的突变率更高（4.3%比 3.6%）。常见的突变是 T1189C/Phe397Leu（34.5%）、T1306C/Phe415Ser（16.0%）和 C1191A/Phe397Leu（11.0%）。在美国患有趾甲甲真菌病的患者中，已经发现了与特比萘芬敏感性降低相关的角鲨烯环氧化酶基因突变。医生应了解耐药发展的危险因素，并采取抗真菌管理实践，如针对皮肤癣菌病和甲真菌病的定向诊断和治疗。
