Department of Botany, Faculty of Science, Charles University, Prague, Czech Republic.
Department of Medical Microbiology Prague and Kladno, Public Health Institute in Ústí nad Labem, Prague, Czech Republic.
Mycoses. 2024 Feb;67(2):e13708. doi: 10.1111/myc.13708.
Terbinafine, an allylamine antifungal, is crucial for treating dermatophytosis by inhibiting squalene epoxidase (SQLE) in the ergosterol biosynthetic pathway. However, resistance is emerging, particularly in India and Southeast Asia, but reports of resistance spread worldwide. Despite this, comprehensive studies on terbinafine resistance in Trichophyton are still limited.
This research aimed to determine the prevalence of terbinafine resistance in the Czech Republic, with a focus on Trichophyton rubrum and Trichophyton mentagrophytes, and investigate the underlying molecular mechanisms.
PATIENTS/METHODS: A total of 514 clinical strains of T. rubrum and 240 T. mentagrophytes collected from four Czech clinical institutions were screened for terbinafine resistance. Molecular investigations included DNA sequencing, specifically the ITS rDNA region and SQLE gene, as well as antifungal susceptibility testing following EUCAST guidelines.
While no resistance was observed in T. rubrum, 2.5% of T. mentagrophytes strains exhibited resistance, marked by the F397L mutation in SQLE. Notably, resistance surged from 1.2% in 2019 to 9.3% in 2020 but reverted to 0% in 2021. All resistant strains were identified as T. mentagrophytes var. indotineae. Resistant strains exhibited high MICs for terbinafine (≥4 mg L ) but low MICs to the other seven antifungals tested except for fluconazole.
This study highlights the emergence of terbinafine-resistant T. mentagrophytes strains in the Czech Republic, with the F397L mutation being pivotal. Due to the relatively low resistance level, the current guidelines for dermatomycosis treatment in the Czech Republic remain effective, but ongoing surveillance is essential for timely adaptations if resistance patterns change.
特比萘芬是一种烯丙胺类抗真菌药物，通过抑制角鲨烯环氧化酶（SQLE）在麦角固醇生物合成途径中发挥作用，对治疗皮肤癣菌病至关重要。然而，耐药性正在出现，特别是在印度和东南亚，但耐药性的报告已经在全球范围内传播。尽管如此，特比萘芬对 Trichophyton 的耐药性的综合研究仍然有限。
本研究旨在确定捷克共和国特比萘芬耐药的流行情况，重点关注红色毛癣菌和须癣毛癣菌，并研究其潜在的分子机制。
患者/方法：从捷克的四家临床机构共筛选了 514 株红色毛癣菌和 240 株须癣毛癣菌临床分离株，以检测其对特比萘芬的耐药性。分子研究包括 DNA 测序，特别是 ITS rDNA 区和 SQLE 基因，以及按照 EUCAST 指南进行的抗真菌药敏试验。
红色毛癣菌中未观察到耐药性，而 2.5%的须癣毛癣菌菌株表现出耐药性，其特征在于 SQLE 中的 F397L 突变。值得注意的是，耐药性从 2019 年的 1.2%飙升至 2020 年的 9.3%，但在 2021 年又降至 0%。所有耐药株均鉴定为须癣毛癣菌 var. indotineae。耐药株对特比萘芬的 MIC 值较高（≥4 mg/L），但对其他七种测试的抗真菌药物的 MIC 值较低，除了氟康唑。
本研究强调了特比萘芬耐药的须癣毛癣菌菌株在捷克共和国的出现，F397L 突变是关键。由于耐药水平相对较低，捷克现行的皮肤癣菌病治疗指南仍然有效，但如果耐药模式发生变化，需要进行持续监测以及时调整。
