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临床重要皮肤癣菌的抗真菌药物敏感性分析及特比萘芬耐药分离株点突变的检测。

Antifungal drug susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates.

机构信息

Department of Mycology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, 14115-331, Iran.

Department of Mycology, Pasteur Institute of Iran, Tehran, 13164, Iran.

出版信息

Eur J Clin Microbiol Infect Dis. 2018 Oct;37(10):1841-1846. doi: 10.1007/s10096-018-3317-4. Epub 2018 Jul 7.

Abstract

With regard to increasing number of antifungal-resistant dermatophytes, antifungal susceptibility testing of dermatophytes serves as a useful tool in managing clinical dermatophytosis. This study aimed to determine antifungal susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates. Based on our results, dermatophytosis was confirmed in 97 cases by direct microscopic examination, culture, and sequencing of ITS region. Antifungal susceptibility of 97 dermatophyte isolates distributed in four species including Trichophyton interdigitale (26 isolates), T. rubrum (19 isolates), T. tonsurans (29 isolates), and Epidermophyton floccosum (21 isolates) was assessed to nine antifungal agents using CLSI M38-A2 guidelines. Minimum inhibitory concentration range (MIC range) for luliconazole and terbinafine was 0.001-0.008 μg/ml and 0.003-> 32 μg/ml, compared to 0.03-64 μg/ml for griseofulvin, 0.01-16 μg/ml for itraconazole and voriconazole, 0.03-8 μg/ml for ketoconazole, 0.03-32 μg/ml for econazole, 0.03-1 μg/ml for lanoconazole, and 0.01-4 μg/ml for butenafine. Trichophyton tonsurans was the most susceptible (MIC = 0.006 μg/ml) and E. floccosum was the most resistant (MIC = 0.02 μg/ml) species to terbinafine. Terbinafine resistance was reported for two species, i.e., T. rubrum and T. tonsurans at the total rate of 2% which was due to Leu393Phe substitution in both species. Taken together, our results assist clinicians and prompt the current knowledge about the necessity of antifungal susceptibility testing to select effective strategies for management of clinical cases of dermatophytosis.

摘要

关于抗真菌药物耐药的皮肤癣菌不断增加,皮肤癣菌的抗真菌药敏试验在管理临床皮肤癣菌病方面是一种有用的工具。本研究旨在确定临床重要皮肤癣菌的抗真菌药敏谱,并确定特比萘芬耐药分离株中的点突变。根据我们的结果,通过直接显微镜检查、培养和 ITS 区测序,在 97 例病例中确认了皮肤癣菌病。用 CLSI M38-A2 指南评估了分布在四个种中的 97 株皮肤癣菌分离株(包括趾间型毛癣菌[26 株]、红色毛癣菌[19 株]、须癣毛癣菌[29 株]和絮状表皮癣菌[21 株])对 9 种抗真菌药物的药敏性。卢立康唑和特比萘芬的最低抑菌浓度范围(MIC 范围)分别为 0.001-0.008μg/ml 和 0.003->32μg/ml,而灰黄霉素为 0.03-64μg/ml,伊曲康唑和伏立康唑为 0.01-16μg/ml,酮康唑为 0.03-8μg/ml,益康唑为 0.03-32μg/ml,克霉唑为 0.03-1μg/ml,布替萘芬为 0.01-4μg/ml。须癣毛癣菌最敏感(MIC=0.006μg/ml),絮状表皮癣菌最耐药(MIC=0.02μg/ml)。特比萘芬耐药报告了两个种,即红色毛癣菌和须癣毛癣菌,总耐药率为 2%,这是由于两个种中的 Leu393Phe 取代所致。总之,我们的结果为临床医生提供了帮助,并提示了目前对抗真菌药敏试验的必要性的认识,以选择治疗皮肤癣菌病临床病例的有效策略。

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