Uhrlaß Silke, Panzer Rüdiger, Koch Daniela, Mütze Hanna, Richter Susanne, Müller Lena, Ardabili Michael, Averbeck Marko, Baldauf Claudia, Batel Janina, Bender-Säbelkampf Sophia, Braun Martin, Bröse Elisabeth, Deutsch Cornelia, Fischer Eleni, Ganser Antje, Geißdörfer Walter, Grigorjan Philipp, Hawlitschek Christina, Hirschsteiner Oliver, Hoffmann Johanna Maria, Hoffmann Michael, Hofmann Silke C, Hradetzky Uta, Huynh Julia, Jansen Martin, Kämmerer Eva, Klonowski Esther, Köhler Lars, Krüger Constanze, Lange Friederike, Maronna Andreas, Marxsen Isabell, Meder Christine, Montag Andreas, Müller Valentina Laura, Nikolakis Georgios, Odon Astrid, Rabe Marie, Rausch Susanne, Ressler Lena, Richter Linda, Schaller Martin, Schäfer Tim, Sinnberg Tobias, Sitaru Cassian, Sticherling Michael, Verma Shyam B, Voigt Floras, Walker Birgit, Wamsler Carolin, Wetzig Tino, Nenoff Pietro
Labor Leipzig-Mölbis, labopart - Medizinische Laboratorien, Partnerschaft Dr. Michael Gerber, Prof. Frank Bühling, Prof. Pietro Nenoff, Tobias Löwe, Erik von Rein, Mölbiser Hauptstr. 8, 04571, Rötha/OT Mölbis, Deutschland.
Klinik und Poliklinik für Dermatologie und Venerologie, Universitätsmedizin Rostock, Strempelstr. 13, 18057, Rostock, Deutschland.
Dermatologie (Heidelb). 2025 Aug 12. doi: 10.1007/s00105-025-05553-6.
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 PheLeu, 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.
须癣毛癣菌ITS基因型VIII/印地毛癣菌（TMVIII/TINDO）是须癣毛癣菌/指间毛癣菌复合体中的一种新型亲人性皮肤癣菌，近年来在全球范围内的重要性日益增加。这种病原体的特征是对特比萘芬耐药频繁，临床表现为明显的、炎症性的且对治疗耐药的皮肤癣菌病，主要累及腹股沟、躯干、四肢和面部。2018年至2024年底，莱比锡 - 默尔比斯实验室系统记录了德国患者中通过培养和/或分子生物学检测到的所有TMVIII/TINDO病例。通过对rDNA的内部转录间隔区（ITS）进行测序来进行鉴定和基因分型。使用断点试验对特比萘芬和伊曲康唑进行体外耐药性检测。此外，对角鲨烯环氧酶（SQLE）基因进行测序以分析与耐药相关的点突变。共鉴定出196例患者的242株分离株；一些患者被连续多次检测到。大多数受影响的患者有移民背景，特别是来自南亚（尤其是印度）和阿拉伯国家。德国血统的患者中仅诊断出少数感染病例。作为诊断检查的一部分，使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株菌株中的161株中发现了与耐药相关的SQLE基因点突变。最常检测到的突变是PheLeu，在所有病例中均与特比萘芬耐药和特比萘芬临床治疗失败相关。此外，在26株菌株中检测到双突变。在186株受试分离株中有11株观察到体外伊曲康唑耐药，占5.9%。伊曲康唑目前是TMVIII/TINDO皮肤癣菌病全身治疗的首选药物。推荐剂量为每日两次，每次100毫克，疗程为4 - 8周，如有需要可长达12周。始终建议同时使用唑类、阿莫罗芬或环吡酮进行局部治疗。如果伊曲康唑治疗失败，目前尚无标准化的治疗建议。在个别病例中曾报道过伏立康唑的超说明书使用情况，并且对其他活性成分也有实验经验。鉴于这种皮肤癣菌对特比萘芬和伊曲康唑的耐药性，TMVIII/TINDO在德国和全球的传播尤其令人担忧。
