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In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of the Mucorales Order

机译:艾沙康康唑和比较剂对粘膜炎临床分离株的体外活性

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摘要

The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5 of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus, 26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC50s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤0.03 to 0.5), 0.06 (≤0.03 to 0.25), and 0.125 (≤0.03 to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively. Isavuconazole activity varied by species: Lichtheimia corymbifera, 1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to 0.5), 1 (0.5 to 2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2 (1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8); and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8), respectively, were more susceptible than Mucor circinelloides: group I, 8 (4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%). Isavuconazole displayed in vitro activity against Mucorales isolates with the exception of Mucor circinelloides. The MICs were in general 1 to 3 steps higher than those for posaconazole. However, in the clinical setting this may be compensated for by the higher exposure at standard dosing.
机译:与两性霉素B,泊沙康唑和伏立康唑相比,通过EUCAST E.Def 9.2和CLSI M38-A2方法测量了伊沙康康唑对毛霉菌分离物的体外活性。包括72种分离株:12个黑夜蛾科,5个拉美假单胞菌,圆环毛霉(Mucor circinelloides)第5组,第I组5个和第II组9个,小根瘤菌9个,小孢子根霉26个和米根霉6个。通过内部转录间隔区(ITS)测序证实了物种鉴定。在第1天(EUCAST-d1)和第2天(EUCAST-d2)读取EUCAST MIC,在第2天(CLSI-d2)读取CLSI MIC。 EUCAST-d1,CLSI-d2和EUCAST-d2的Isavuconazole MIC50(范围)(mg / L)分别为1(0.125至16),1(0.125至2)和4(0.5至> 16)所有分离物。比较药物的相似值如下:泊沙康唑,0.25(≤0.03至> 16),0.25(0.06至> 16)和1(0.06至> 16);两性霉素0.06(≤0.03至0.5),0.06(≤0.03至0.25)和0.125(≤0.03至1);伏立康唑分别为16(2至> 16),8(1至> 16)和> 16(8至> 16)。依沙康康唑的活性因物种而异:紫薇,1(0.5至2),1(1至2)和2(1至4); ramchtheimia ramosa,0.25(0.125至0.5),1(0.5至2)和2(0.5至4);根瘤菌(Rhizomucor pusillus)0.5(0.5至1),1(0.125至1)和2(1至2);微孢菌根霉,1(0.5至4),0.5(0.125至1)和4(1至8);和米根霉(Rhizopus oryzae)分别比圆环毛霉菌(Mucor circinelloides)更易感(1(0.5至4),1(0.125至2)和4(0.5至8)):第I,8(4至8),4(2至4) )和16(2至16),以及组II,8(1至16),8(1至8)和16(4至> 16)。泊沙康唑也观察到了这一点。 EUCAST-d1和CLSI-d2之间最好的协议是最好的协议(75%至83%)。 Isavuconazole表现出对Mucorales分离株的体外活性,除了 Mucor circinelloides 。 MIC通常比泊沙康唑的MIC高1到3步。但是,在临床环境中,这可以通过标准剂量下的较高暴露量来补偿。

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