Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Spanish Network for Research in Infectious Diseases (REIPI RD16/CIII/0004/0003), Instituto de Salud Carlos III, Madrid, Spain.
J Antimicrob Chemother. 2020 Dec 1;75(12):3582-3585. doi: 10.1093/jac/dkaa351.
To evaluate the in vitro activity of olorofim, a new broad-spectrum antifungal with a novel mechanism of action, against a collection of 123 Spanish clinical isolates belonging to five Scedosporium species and Lomentospora prolificans.
The activity of olorofim against Scedosporium apiospermum (n = 30), Scedosporium boydii (n = 30), Scedosporium ellipsoideum (n = 10), Scedosporium aurantiacum (n = 20), Scedosporium dehoogii (n = 3) and Lomentospora prolificans (n = 30) was compared with that of amphotericin B, voriconazole, isavuconazole and micafungin by performing EUCAST and CLSI reference methods for antifungal susceptibility testing.
Amphotericin B and isavuconazole showed MICs ≥2 mg/L for all the species evaluated and voriconazole was moderately active (GM, MIC50 and MIC90 values ≤2 mg/L) against all of them except L. prolificans. Micafungin was effective against S. apiospermum complex strains, but exhibited elevated MECs for S. dehoogii and S. aurantiacum. Olorofim showed low MICs for all the Scedosporium strains tested (GM values were lower than 0.130 and 0.339 by the EUCAST method and the CLSI method, respectively, for all of the species), including those belonging to the MDR species L. prolificans, for which GM values were 0.115 and 0.225 mg/L by the EUCAST method and the CLSI method, respectively, while the GMs for the rest of the antifungals evaluated were higher than 3.732 mg/L using both methodologies.
Olorofim displayed promising in vitro activity against the Scedosporium and L. prolificans strains tested, some of which have reduced susceptibility to the antifungals that are currently in use.
评估新型广谱抗真菌药物olorofim 的体外活性，该药物具有新颖的作用机制，针对属于 5 种棘白菌素属物种和 Lomentospora prolificans 的 123 株西班牙临床分离株。
通过执行 EUCAST 和 CLSI 抗真菌药敏检测参考方法，比较 olorofim 对棘孢木霉（n=30）、博伊丁棘孢霉（n=30）、椭圆棘孢霉（n=10）、橙色棘孢霉（n=20）、dehoogii 棘孢霉（n=3）和 prolificans 木霉（n=30）的活性与两性霉素 B、伏立康唑、伊曲康唑和米卡芬净的活性。
两性霉素 B 和伊曲康唑对所有评估的物种的 MICs 值均≥2mg/L，伏立康唑对除 prolificans 木霉以外的所有物种均具有中度活性（GM 值、MIC50 和 MIC90 值均≤2mg/L）。米卡芬净对棘孢木霉复合体菌株有效，但对 dehoogii 棘孢霉和橙色棘孢霉的 MIC 较高。olorofim 对所有测试的棘孢霉菌株均显示出较低的 MIC 值（根据 EUCAST 方法，GM 值均低于 0.130 和 0.339，根据 CLSI 方法，所有物种的 GM 值均低于 0.115 和 0.225mg/L），包括属于多药耐药物种 prolificans 木霉的菌株，根据 EUCAST 方法和 CLSI 方法，GM 值分别为 0.115 和 0.225mg/L，而评估的其余抗真菌药物的 GM 值均高于 3.732mg/L。
olorofim 对测试的棘孢霉和 prolificans 菌株显示出有希望的体外活性，其中一些菌株对目前使用的抗真菌药物的敏感性降低。
