[在德国发现的mentagrophytes ITS基因型VIII/ indotinetrichophyton - 5年后再访]。

IF 0.7
Dermatologie (Heidelberg, Germany) Pub Date : 2025-09-01 Epub Date: 2025-08-12 DOI:10.1007/s00105-025-05553-6
Silke Uhrlaß, Rüdiger Panzer, Daniela Koch, Hanna Mütze, Susanne Richter, Lena Müller, Michael Ardabili, Marko Averbeck, Claudia Baldauf, Janina Batel, Sophia Bender-Säbelkampf, Martin Braun, Elisabeth Bröse, Cornelia Deutsch, Eleni Fischer, Antje Ganser, Walter Geißdörfer, Philipp Grigorjan, Christina Hawlitschek, Oliver Hirschsteiner, Johanna Maria Hoffmann, Michael Hoffmann, Silke C Hofmann, Uta Hradetzky, Julia Huynh, Martin Jansen, Eva Kämmerer, Esther Klonowski, Lars Köhler, Constanze Krüger, Friederike Lange, Andreas Maronna, Isabell Marxsen, Christine Meder, Andreas Montag, Valentina Laura Müller, Georgios Nikolakis, Astrid Odon, Marie Rabe, Susanne Rausch, Lena Ressler, Linda Richter, Martin Schaller, Tim Schäfer, Tobias Sinnberg, Cassian Sitaru, Michael Sticherling, Shyam B Verma, Floras Voigt, Birgit Walker, Carolin Wamsler, Tino Wetzig, Pietro Nenoff
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引用次数: 0

摘要

毛癣菌(T.): ITS基因型VIII/T。indotineae (TMVIII/TINDO)是一种新发现的嗜人皮肤真菌。近年来在世界范围内越来越受到重视的跨数综合体。这种病原体的特点是经常对特比萘芬耐药,临床表现为明显的炎症性和耐药性皮肤真菌病,主要影响腹股沟、躯干、四肢和面部。2018年至2024年底,在Leipzig-Mölbis实验室系统记录了通过培养和/或分子生物学在德国患者中检测到的所有TMVIII/TINDO病例。通过对rDNA的内部转录间隔区(ITS)进行测序进行鉴定和基因分型。采用断点法对特比萘芬和伊曲康唑进行体外耐药试验。此外,对角鲨烯环氧化酶(SQLE)基因进行测序以分析抗性相关的点突变。196例患者共分离242株;部分患者连续反复检测。大多数受影响的患者具有移民背景,特别是来自南亚(特别是印度)和阿拉伯国家。只有少数德国血统的患者被诊断出感染。作为诊断工作的一部分,采用断点试验进行了体外药敏试验,结果显示61.8%的TMVIII/TINDO菌株对特比萘芬耐药。在188个菌株中,共有161个菌株存在与耐药性相关的SQLE基因点突变。最常见的突变为Phe397Leu,所有病例均与特比萘芬耐药和特比萘芬临床治疗失败有关。另外,在26株菌株中检测到双突变。186株分离菌中有11株对伊曲康唑耐药,占5.9%。伊曲康唑是目前治疗TMVIII/TINDO皮肤病的首选药物。推荐剂量为100 mg,每日两次,持续4-8周,如有需要可延长至12周。同时局部治疗与唑,阿莫罗芬,或环匹洛克斯总是推荐。在伊曲康唑治疗失败的情况下,目前没有标准化的治疗建议。伏立康唑的超说明书使用在个别病例中有报道,其他活性成分也有实验经验。鉴于皮肤真菌对特比萘芬和伊曲康唑的耐药性,TMVIII/TINDO在德国和世界范围内的传播尤其令人担忧。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Trichophyton mentagrophytes ITS genotype VIII/Trichophyton indotineae in Germany-revisit after 5 years].

Trichophyton (T.) mentagrophytes ITS genotype VIII/T. indotineae (TMVIII/TINDO) is a new, anthropophilic dermatophyte from the T. mentagrophytes/T. interdigitale complex that has gained increasing importance worldwide in recent years. This pathogen is characterized by frequent terbinafine resistance and a clinical picture of pronounced, inflammatory, and therapy-resistant dermatophytoses that predominantly affect the groin, trunk, extremities, and face. Between 2018 and the end of 2024, all TMVIII/TINDO cases detected in patients from Germany by culture and/or molecular biology were systematically recorded at the Leipzig-Mölbis laboratory. Identification and genotyping were performed by sequencing the internal transcribed spacer (ITS) region of the rDNA. In vitro resistance testing for terbinafine and itraconazole was performed using a breakpoint test. Additionally, the squalene epoxidase (SQLE) gene was sequenced to analyze resistance-associated point mutations. A total of 242 isolates from 196 patients were identified; some patients were consecutively detected repeatedly. The majority of affected patients had a migration background, particularly from South Asia (especially India) and Arab countries. Only a few infections were diagnosed in patients of German descent. As part of the diagnostic workup an in vitro susceptibility testing was performed using a breakpoint test, which demonstrated terbinafine resistance in 61.8% of the TMVIII/TINDO strains. Point mutations in the SQLE gene that correlated with resistance were found in a total of 161 of 188 strains. The most frequently detected mutation was Phe397Leu, which was associated with terbinafine resistance and clinical treatment failure with terbinafine in all cases. In addition, double mutations were detected in 26 strains. In vitro itraconazole resistance was observed in 11 of 186 tested isolates, corresponding to 5.9%. Itraconazole is currently the drug of choice for the systemic treatment of TMVIII/TINDO dermatophytoses. The recommended dosage is 100 mg twice daily for a period of 4-8 weeks, or up to 12 weeks if needed. Concurrent topical treatment with azoles, amorolfine, or ciclopirox is always recommended. In the event of itraconazole treatment failure, there are currently no standardized treatment recommendations. The off-label use of voriconazole has been reported in isolated cases, and there is also experimental experience with other active ingredients. The spread of TMVIII/TINDO in Germany and worldwide is particularly worrying in view of the dermatophyte's resistance to terbinafine and itraconazole.

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