ATI-2307 Exhibits Equivalent Antifungal Activity in Cryptococcus neoformans Clinical Isolates With High and Low Fluconazole IC(50).
ATI-2307 Exhibits Equivalent Antifungal Activity in Cryptococcus neoformans Clinical Isolates With High and Low Fluconazole IC(50).
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DOI：
10.3389/fcimb.2021.695240
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发表时间：
2021
影响因子：
5.7
通讯作者：
Nielsen K
中科院分区：
文献类型：
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作者：
Gerlach ES;Altamirano S;Yoder JM;Luggya TS;Akampurira A;Meya DB;Boulware DR;Rhein J;Nielsen K
用微量肉汤稀释法测定了69株临床分离的新生隐球菌对实验药物ATI-2307的半数最大抑菌浓度(IC50)和临床常用抗真菌药物两性霉素B的完全抑制(IC90)。大多数临床分离株对氟康唑的IC50为8微克/毫升或以上，但对两性霉素B(IC_(90)≤1μ/毫升)和ATI2307(IC_(50)≤为0.0312微克/毫升)均敏感。氟康唑最低抑菌浓度(MIC)的升高与ATI-2307或两性霉素B的MIC无相关性，提示影响氟康唑敏感性的细胞变化不影响ATI-2307的药效。我们的结果表明，ATI-2307是一种很有前途的新的抗真菌药物，可用于高氟康唑或其他抗真菌药物的MIC和/或联合用药方案。
Half maximal inhibitory concentrations (IC50) to the experimental drug ATI-2307 and complete inhibition (IC90) of the common clinically used antifungal drug amphotericin B were determined by microbroth dilution assay for a collection of 69 clinical isolates of Cryptococcus neoformans from Uganda that had high fluconazole IC50 values. The majority of the clinical isolates tested had fluconazole IC50 at or above 8 µg/mL, but were susceptible to both amphotericin B (IC90 ≤1 μg/mL) and ATI-2307 (IC50 ≤0.0312 µg/mL). No correlation between increased fluconazole minimum inhibitory concentration (MIC) and ATI-2307 or amphotericin B MIC was observed, suggesting that the cellular changes impacting fluconazole susceptibility did not impact the effectiveness of ATI-2307. Our results suggest that ATI-2307 is a promising new antifungal drug for use in the context of high fluconazole or other antifungal drug MICs and/or in combination drug therapy regimens.