Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Antimicrob Agents Chemother. 2020 Feb 21;64(3). doi: 10.1128/AAC.02136-19.
Ibrexafungerp (SCY-078) is a novel first-in-class antifungal agent targeting glucan synthase. is an emerging multidrug-resistant species that has caused outbreaks on five continents. We investigated the activity of ibrexafungerp against by applying EUCAST E.Def 7.3.1 methodology. and , as well as anidulafungin, micafungin, amphotericin B, fluconazole, voriconazole, and isavuconazole, were included as comparators. Three reference strains (CBS12372, CBS12373, and CBS10913) and 122 , 16 , and 16 isolates were evaluated. ATCC 64548, ATCC 22019, and ATCC 6258 served as quality control strains. Echinocandin-resistant isolates were sequenced. MIC ranges and modal MIC and MIC values were determined. Wild-type upper limits (the upper MIC value where the wild-type distribution ends) were determined according to EUCAST principles for setting ECOFFs. Nine repetitions of three QC strains and MICs for and yielded narrow MIC ranges with modal MICs in agreement with established EUCAST modal MICs, confirming a robust test performance. The ibrexafungerp MICs against isolates displayed a Gaussian distribution with a modal MIC (range) of 0.5 mg/liter (0.06 to 2 mg/liter), suggesting uniform susceptibility. Of 122 isolates, 8 were echinocandin resistant and harbored the S639F Fks1 alteration. All but one were fluconazole resistant, and the MIC distributions for voriconazole and isavuconazole were multimodal confirming variable susceptibility. Ibrexafungerp demonstrated promising activity against , including isolates resistant to echinocandins and/or other agents. The MICs were similar to those reported for the Clinical and Laboratory Standards Institute method, suggesting that a common clinical breakpoint may be appropriate.
依布硒康唑（SCY-078）是一种新型的靶向葡聚糖合酶的首创抗真菌药物。近平滑念珠菌是一种新兴的多药耐药物种，已在五大洲引发了疫情。我们应用 EUCAST E.Def 7.3.1 方法，研究了依布硒康唑对近平滑念珠菌的活性。作为对照，我们纳入了阿尼芬净、米卡芬净、两性霉素 B、氟康唑、伏立康唑和伊曲康唑。评估了三个近平滑念珠菌参考菌株（CBS12372、CBS12373 和 CBS10913）和 122 个、16 个和 16 个分离株。ATCC 64548、ATCC 22019 和 ATCC 6258 作为质控菌株。对棘白菌素耐药的分离株进行了测序。测定了 MIC 范围、模态 MIC 和 MIC 值。根据建立 ECOFF 的 EUCAST 原则，确定了野生型上限（野生型分布结束的最高 MIC 值）。三个质控菌株的 MIC 重复 9 次，且与已建立的 EUCAST 模态 MIC 一致，表明模态 MIC 值与依布硒康唑一致，这证实了检测方法性能稳健。依布硒康唑对近平滑念珠菌分离株的 MIC 呈正态分布，模态 MIC（范围）为 0.5mg/L（0.06-2mg/L），提示具有均匀的敏感性。在 122 个分离株中，8 个为棘白菌素耐药，携带 S639F Fks1 突变。除 1 个分离株外，其余均对氟康唑耐药，伏立康唑和伊曲康唑的 MIC 分布呈多峰，证实了可变的敏感性。依布硒康唑对近平滑念珠菌具有良好的活性，包括对棘白菌素和/或其他药物耐药的分离株。MIC 值与临床和实验室标准协会方法报道的相似，这表明可能需要一个共同的临床折点。
