EUCAST Determination of Olorofim (F901318) Susceptibility of Mold Species, Method Validation, and MICs.
EUCAST Determination of Olorofim (F901318) Susceptibility of Mold Species, Method Validation, and MICs.
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DOI：
10.1128/aac.00487-18
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发表时间：
2018-08-01
影响因子：
4.9
通讯作者：
Arendrup, Maiken Cavling
中科院分区：
文献类型：
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作者：
Jorgensen, Karin Meinike;Astvad, Karen M T;Arendrup, Maiken Cavling
奥洛菲姆是一种新型的抗真菌药物，对曲霉等霉菌具有体外抗菌活性。在这里，我们讨论了EUCAST olorofim测试的技术方面，并生成了当代MIC数据。进行EUCAST E.Def 9.3.1试验，比较两种平板制备方法(在介质[连续平板]中连续稀释与在DMSO[ISO平板]中预稀释)、两批olorofim、目视(视觉-MIC)与分光光度(SPEC-MIC)读数，以及使用来自5个属的34至53个曲霉菌株的4个聚苯乙烯平板。随后，对298株临床分离的霉菌(2016-2017)进行了olorofim与伊曲康唑、伏立康唑、泊沙康唑和两性霉素B的MICs比较。野生型上限(WT-UL)的确定遵循EUCAST的流行病学截断值设定原则(ECOFF)。Olorofim系列纸片与ISO纸片的MIC中位数相同(25/36[69%])或1倍稀释(11/36[31%])。对于≤1/≤2稀释液，人与人之间对视觉MIC的符合率分别为92%至94%/100%。在测试的微滴定板和奥罗菲姆批次上的视觉MIC值仅显示离散的差异(处理的板的≤1稀释度更低)。没有单一的SPEC-MIC标准适用于所有物种。Olorofim对2 75株曲霉菌的MIC值较低(MODEL MIC0.06 mg/L；MIC值范围：0.004~0.25mgL/L)和3种皮肤真菌(MIC0.03~0.06mgL/L)。对镰刀菌的最低抑菌浓度(MIC)表现出多样性，对增殖镰刀菌的最低抑菌浓度(MIC，0.016)，对茄病镰刀菌的生长抑制率为50%(1~2 mg/L)，对二聚体镰刀菌无抑制作用，对大多数霉菌表现出较强的体外抑制活性，并与EUCAST敏感性试验的变异有限有关。
Olorofim is a novel antifungal agent with in vitro activity against Aspergillus and some other molds. Here, we addressed technical aspects for EUCAST olorofim testing and generated contemporary MIC data. EUCAST E.Def 9.3.1 testing was performed comparing two plate preparation methods (serial dilution in medium [serial plates] versus predilution in DMSO [ISO plates]), two lots of olorofim, visual (visual-MIC) versus spectrophotometer (spec-MIC) reading, and four polystyrene plates using 34 to 53 Aspergillus isolates from five genera. Subsequently, olorofim MICs were compared to itraconazole, voriconazole, posaconazole, and amphotericin B MICs for 298 clinical mold isolates (2016 to 2017). Wild-type upper limits (WT-UL) were determined following EUCAST principles for epidemiologic cutoff value (ECOFF) setting. Olorofim median MICs comparing serial plates and ISO plates were identical (25/36 [69%]) or one dilution apart (11/36 [31%]). Interperson agreement for visual-MICs was 92% to 94%/100% for ≤1/≤2 dilutions, respectively. The visual-MIC values across tested microtiter plates and olorofim lots revealed only discrete differences (≤1 dilution lower for treated plates). No single spec-MIC criterion was applicable to all species. Olorofim MICs were low against 275 Aspergillus species isolates (modal MIC, 0.06 mg/liter; MIC range, < 0.004 to 0.25 mg/liter) and three dermatophytes (MICs 0.03 to 0.06 mg/liter). MICs against Fusarium were diverse, with full inhibition of F. proliferatum (MIC, 0.016), 50% growth inhibition of Fusarium solani at 1 to 2 mg/liter, and no inhibition of F. dimerum Olorofim displayed potent in vitro activity against most mold isolates and was associated with limited variation in EUCAST susceptibility testing.