Garbe Enrico, Ullah Ahsan, Aldejohann Alexander Maximilian, Kurzai Oliver, Janevska Slavica, Walther Grit
(Epi-)Genetic Regulation of Fungal Virulence, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.
Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.
Antimicrob Agents Chemother. 2025 Jun 4;69(6):e0191324. doi: 10.1128/aac.01913-24. Epub 2025 May 15.
The genus includes several trans-kingdom pathogens, infecting plants, animals, and humans, with widespread occurrence. Invasive infections are often destructive due to their prevalence in critically ill patients. Furthermore, severe superficial infections, like keratitis or endophthalmitis with potential loss of vision, are rising in incidence globally. Infections are difficult to treat due to the intrinsic resistance of against echinocandins and often high minimal inhibitory concentrations (MICs) for azoles. In this article, we assessed the activity of the novel antifungals olorofim, manogepix, rezafungin, and ibrexafungerp, as well as the established but nonstandard drugs, natamycin and terbinafine, against a large set of molecularly identified clinical isolates via EUCAST microdilution. The tested isolates represent the clinically most relevant species of the (FSSC), (FOSC), (FFSC), (FIESC), (FDSC), and (FRSC) species complexes. While rezafungin and ibrexafungerp showed no effect on the spp. tested, a general antifungal susceptibility of against natamycin and manogepix was found. Specific profiles were detailed for terbinafine and olorofim. While species from the FDSC, FSSC, and FIESC show high MICs for olorofim, specific susceptibility rates were found for species of the FFSC and FOSC. Furthermore, we report specific susceptibilities for terbinafine against FDSC, FFSC, and FOSC species. These findings of complex- and species-specific olorofim and terbinafine susceptibilities highlight the need for diagnostics below genus level.
该属包括几种跨界病原体，可感染植物、动物和人类，广泛存在。侵袭性感染在重症患者中很常见，往往具有破坏性。此外，严重的浅表感染，如可能导致视力丧失的角膜炎或眼内炎，在全球范围内的发病率正在上升。由于对棘白菌素具有内在抗性，且对唑类药物的最低抑菌浓度（MIC）通常较高，这些感染难以治疗。在本文中，我们通过欧洲抗菌药物敏感性试验委员会（EUCAST）微量稀释法，评估了新型抗真菌药物奥拉氟米、马尼戈派克斯、瑞扎芬净和依布雷xafungerp，以及已确立但非标准的药物那他霉素和特比萘芬，对大量经分子鉴定的临床分离株的活性。测试的分离株代表了临床上最相关的镰刀菌属复合体的物种，包括尖孢镰刀菌复合体（FSSC）、茄病镰刀菌复合体（FOSC）、串珠镰刀菌复合体（FFSC）、拟枝孢镰刀菌复合体（FIESC）、层出镰刀菌复合体（FDSC）和腐皮镰刀菌复合体（FRSC）。虽然瑞扎芬净和依布雷xafungerp对测试的镰刀菌属物种没有效果，但发现镰刀菌属对那他霉素和马尼戈派克斯具有普遍的抗真菌敏感性。详细描述了特比萘芬和奥拉氟米的具体药敏谱。虽然来自FDSC、FSSC和FIESC的物种对奥拉氟米显示出高MIC，但发现FFSC和FOSC的物种有特定的药敏率。此外我们报告了特比萘芬对FDSC、FFSC和FOSC物种的特异性敏感性。这些关于奥拉氟米和特比萘芬对复合体和物种的特异性药敏结果，凸显了进行属以下水平诊断的必要性。
