Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
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.
RESULTS: 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-1 ) but low MICs to the other seven antifungals tested except for fluconazole.
CONCLUSIONS: 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.
OBJECTIVE: 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.
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.
RESULTS: 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-1 ) but low MICs to the other seven antifungals tested except for fluconazole.
CONCLUSIONS: 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.
摘要：
背景：特比萘芬，烯丙胺抗真菌药,对于通过抑制麦角甾醇生物合成途径中的角鲨烯环氧酶（SQLE）来治疗皮肤癣菌病至关重要。然而,抵抗正在出现，尤其是在印度和东南亚，但是有关抗药性的报道在全世界蔓延。尽管如此,关于毛癣菌特比萘芬耐药性的综合研究仍然有限。
目的：本研究旨在确定捷克共和国特比萘芬耐药性的患病率，重点研究红色毛癣菌和毛癣菌，并研究潜在的分子机制。
方法：对从四个捷克临床机构收集的514株红斑毛虫和240株绿斑毛虫进行了特比萘芬抗性筛选。分子调查包括DNA测序，特别是ITSrDNA区域和SQLE基因，以及符合EUCAST指南的抗真菌药敏试验。
结果：虽然在红毛虫中没有观察到耐药性，2.5%的植叶草菌株表现出抗性，以SQLE中的F397L突变为标志。值得注意的是,阻力从2019年的1.2%飙升至2020年的9.3%，但在2021年恢复至0%。所有抗性菌株均被鉴定为T.mentagrosphytesvar。吲哚科.耐药菌株对特比萘芬的MIC较高（≥4mgL-1），但对除氟康唑外的其他7种抗真菌药的MIC较低。
结论：这项研究强调了在捷克共和国出现的耐特比萘芬T.mentagrophytes菌株，F397L突变是关键的。由于电阻水平相对较低，捷克共和国目前的皮肤真菌病治疗指南仍然有效，但是如果抵抗模式发生变化，持续的监测对于及时适应至关重要。
目的：本研究旨在确定捷克共和国特比萘芬耐药性的患病率，重点研究红色毛癣菌和毛癣菌，并研究潜在的分子机制。
方法：对从四个捷克临床机构收集的514株红斑毛虫和240株绿斑毛虫进行了特比萘芬抗性筛选。分子调查包括DNA测序，特别是ITSrDNA区域和SQLE基因，以及符合EUCAST指南的抗真菌药敏试验。
结果：虽然在红毛虫中没有观察到耐药性，2.5%的植叶草菌株表现出抗性，以SQLE中的F397L突变为标志。值得注意的是,阻力从2019年的1.2%飙升至2020年的9.3%，但在2021年恢复至0%。所有抗性菌株均被鉴定为T.mentagrosphytesvar。吲哚科.耐药菌株对特比萘芬的MIC较高（≥4mgL-1），但对除氟康唑外的其他7种抗真菌药的MIC较低。
结论：这项研究强调了在捷克共和国出现的耐特比萘芬T.mentagrophytes菌株，F397L突变是关键的。由于电阻水平相对较低，捷克共和国目前的皮肤真菌病治疗指南仍然有效，但是如果抵抗模式发生变化，持续的监测对于及时适应至关重要。
