Arendrup Maiken Cavling, Jensen Rasmus Hare, Meletiadis Joseph
Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark
Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark.
Antimicrob Agents Chemother. 2015 Dec;59(12):7735-42. doi: 10.1128/AAC.01919-15. Epub 2015 Oct 5.
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.
研究了依沙康唑对毛霉目分离株的体外活性，采用欧洲抗菌药物敏感性试验委员会（EUCAST）E.Def 9.2和美国临床和实验室标准协会（CLSI）M38 - A2方法进行测定，并与两性霉素B、泊沙康唑和伏立康唑进行比较。纳入了72株分离株：12株伞枝梨头霉、5株总状梨头霉、5株卷枝毛霉I组和9株卷枝毛霉II组、9株微小根毛霉、26株少根根霉和6株米根霉。通过内转录间隔区（ITS）测序确认菌种鉴定。EUCAST最低抑菌浓度（MIC）在第1天（EUCAST - d1）和第2天（EUCAST - d2）读取，CLSI MIC在第2天（CLSI - d2）读取。依沙康唑在EUCAST - d1、CLSI - d2和EUCAST - d2时的MIC50（范围）（mg/L）在所有分离株中分别为1（0.125至16）、1（0.125至2）和4（0.5至>16）。对照药物的相似值如下：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，16（2至>16）、8（1至>16）和>16（8至>16）。依沙康唑的活性因菌种而异：伞枝梨头霉，1（0.5至2）、1（1至2）和2（1至4）；总状梨头霉，0.25（0.125至0.5）、1（0.5至2）和2（0.5至4）；微小根毛霉，0.5（0.5至1）、1（0.125至1）和2（1至2）；少根根霉，1（0.5至4）、0.5（0.125至1）和4（1至8）；米根霉，1（0.5至4）、1（0.125至2）和4（0.5至8），分别比卷枝毛霉更敏感：I组，分别为8（4至8）、4（2至4）和16（2至16），II组，分别为8（1至16）、8（1至8）和16（
