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由红色毛癣菌引起的特比萘芬耐药皮肤癣菌病和甲癣

[Terbinafine-resistant dermatophytoses and onychomycosis due to Trichophyton rubrum].

作者信息

Appelt L, Nenoff P, Uhrlaß S, Krüger C, Kühn P, Eichhorn K, Buder S, Beissert S, Abraham S, Aschoff R, Bauer A

机构信息

Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus, Technische Universität, Fetscherstr. 74, 01307, Dresden, Deutschland.

Labor für medizinische Mikrobiologie, Mölbis, Deutschland.

出版信息

Hautarzt. 2021 Oct;72(10):868-877. doi: 10.1007/s00105-021-04879-1. Epub 2021 Aug 30.

Abstract

BACKGROUND

In recent years, therapy-refractory courses of dermatophytoses have increasingly become the focus of attention. The most frequent pathogens are Trichophyton (T.) rubrum and T. mentagrophytes. In addition to local therapy, first-line treatment includes terbinafine, an allylamine antifungal agent that acts by inhibiting squalene epoxidase and thus interfering with ergosterol synthesis. In refractory cases, terbinafine resistance due to point mutation in the squalene epoxidase gene has been frequently detected.

OBJECTIVES

The aim is to present specific aspects in the epidemiology of dermatophytoses with terbinafine resistance and to illustrate them on the basis of four patient cases including diagnostic procedures.

MATERIALS AND METHODS

A review of handbook knowledge, a selective literature search, and a review of four patient cases were performed.

RESULTS

Detection of the terbinafine resistance was performed by in vitro testing using the breakpoint method as well as sequencing of the Trichophyton isolate and detection of the point mutation with amino acid substitution at position L393F or F397L of squalene epoxidase.

CONCLUSION

In refractory and recurrent dermatophytoses, terbinafine resistance should be considered, especially in T. mentagrophytes and T. rubrum, and in vitro resistance testing of the dermatophyte and point mutation analysis of squalene epoxidase (SQLE) should be performed. Therapeutically, intermittent administration of itraconazole in combination with antifungal local therapy is recommended. Nevertheless, a recurrent course is to be expected and long-term therapy with itraconazole is usually necessary.

摘要

背景

近年来,难治性皮肤癣菌病病程日益成为关注焦点。最常见的病原体是红色毛癣菌和须癣毛癣菌。除局部治疗外,一线治疗包括特比萘芬,一种烯丙胺类抗真菌药,其作用机制是抑制角鲨烯环氧酶,从而干扰麦角固醇合成。在难治性病例中,经常检测到由于角鲨烯环氧酶基因突变导致的特比萘芬耐药。

目的

旨在介绍具有特比萘芬耐药性的皮肤癣菌病流行病学的具体方面,并通过包括诊断程序在内的4例患者病例进行说明。

材料与方法

进行了手册知识回顾、选择性文献检索以及4例患者病例回顾。

结果

采用断点法体外检测、对皮肤癣菌分离株进行测序以及检测角鲨烯环氧酶L393F或F397L位置氨基酸替代的点突变来检测特比萘芬耐药性。

结论

在难治性和复发性皮肤癣菌病中,应考虑特比萘芬耐药性,尤其是对于须癣毛癣菌和红色毛癣菌,应进行皮肤癣菌的体外耐药性检测和角鲨烯环氧酶(SQLE)的点突变分析。在治疗上,建议伊曲康唑间歇给药联合局部抗真菌治疗。然而,预计会出现复发病程,通常需要伊曲康唑长期治疗。

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