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APX001A 对欧盟药敏试验委员会参考方法检测的当代血培养分离株和耳念珠菌的活性。

APX001A Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method.

机构信息

Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark

Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.

出版信息

Antimicrob Agents Chemother. 2018 Sep 24;62(10). doi: 10.1128/AAC.01225-18. Print 2018 Oct.

Abstract

APX001A is the active moiety of the first-in-class drug candidate APX001. So far, most susceptibility testing studies have examined ≤30 isolates/species, and only one used the EUCAST method. Here, we investigated the activity of APX001A and five comparators against 540 candidemia and 122 isolates. Isolates (17 and 3 yeast species) were identified using CHROMagar, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) and, when needed, internal transcribed space (ITS) sequencing. EUCAST E.Def 7.3.1 susceptibility testing included APX001A, amphotericin B, anidulafungin, micafungin, fluconazole, and voriconazole. Wild-type upper limits (WT-UL) were established following the EUCAST principles for epidemiological cutoff value setting for APX001A, allowing classification as wild type (WT) or non-WT. APX001A MIC values (mg/liter) were as follows: , , and , 0.004 to 0.008; and , 0.016; , 0.06; and , >0.5. APX001A MICs against the rare species varied from ≤0.0005 () to >0.5 (). APX001A was equally or more active than the comparators against all species except and Four isolates were APX001A non-WT; all were fluconazole resistant. A correlation was observed between APX001A and fluconazole MICs across all species except and , and when comparing high and low fluconazole MIC isolates of , , , , and APX001A showed promising activity against most and other yeast species, including , compared to five comparators. WT-UL were suggested for the common species, and a new and unexplained correlation to fluconazole susceptibility was observed.

摘要

APX001A 是首个同类药物候选物 APX001 的有效成分。到目前为止,大多数药敏试验研究都只检测了 ≤30 株/种的分离株,且只有一项研究使用了 EUCAST 方法。在这里,我们研究了 APX001A 和五种对照药物对 540 株菌血症和 122 株分离株的活性。采用 CHROMagar、基质辅助激光解吸电离飞行时间质谱(MALDI-TOF)和必要时内部转录间隔区(ITS)测序来鉴定分离株(17 株和 3 种酵母种)。EUCAST E.Def 7.3.1 药敏试验包括 APX001A、两性霉素 B、阿尼芬净、米卡芬净、氟康唑和伏立康唑。根据 APX001A 流行病学折点设定的 EUCAST 原则建立了野生型上限(WT-UL),允许分类为野生型(WT)或非野生型(non-WT)。APX001A 的 MIC 值(mg/L)如下:、、、和,0.004 至 0.008;和,0.016;、和,0.06;和,>0.5。APX001A 对罕见种的 MIC 值从≤0.0005()到>0.5()不等。APX001A 对所有种的活性与对照药物相当或更高,除了和。四种分离株为 APX001A 非野生型;均对氟康唑耐药。除了和,在所有种中观察到 APX001A 与氟康唑 MIC 之间存在相关性,在比较、、、和中高氟康唑 MIC 分离株时,APX001A 对大多数念珠菌和其他酵母种显示出有前途的活性,与五种对照药物相比。对常见种提出了 WT-UL,并且观察到与氟康唑药敏性的新的和未解释的相关性。

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