Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Antimicrob Agents Chemother. 2018 Sep 24;62(10). doi: 10.1128/AAC.01225-18. Print 2018 Oct.
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.
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。