Abstract

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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使用EUCAST和CLSI方法，奥洛洛芬对Scedosporium物种和Lomentospora prolificans的临床分离株的体外活性。

摘要

目标

为了评估具有新型作用机制的新型广谱抗真菌药olorofim的体外活性，该菌对123种来自西班牙的5种Scedosporium物种和Lomentospora prolificans的临床分离株具有一定的作用。

方法

olorofim的对抗活性足放线病菌赛多孢子菌（Ñ  = 30），足放线病菌鲍氏（Ñ  = 30），足放线病菌ellipsoideum（Ñ  = 10），足放线病菌aurantiacum菌（Ñ  = 20），足放线病菌dehoogii（Ñ  = 3）和Lomentospora prolificans（Ñ  =通过执行EUCAST和CLSI参考方法进行抗真菌药敏试验，将30）与两性霉素B，伏立康唑，伊沙康康唑和米卡芬净进行比较。

结果

两性霉素B和艾沙康唑表明MIC值≥2毫克/升的所有物种评价和伏立康是中等活性（GM，MIC ₅₀和MIC _90个值≤2毫克/升）对所有的人除了L. prolificans。米卡芬净可以有效地对抗S. apiospermum复合菌株，但对dehoogii和S. aurantiacum的MEC升高。Olorofim对所有经测试的Scedosporium菌株均显示出较低的MIC（对于所有物种而言，通过EUCAST方法和CLSI方法得出的GM值分别低于0.130和0.339），包括属于多药多杀菌L. prolificans的那些，通过EUCAST方法和CLSI方法得出的GM值分别为0.115和0.225 mg / L，而使用这两种方法评估的其余抗真菌剂的GM均高于3.732 mg / L。

结论

Olorofim表现出对测试的Scedosporium和L. prolificans菌株有希望的体外活性，其中一些降低了对目前使用的抗真菌药的敏感性。