Medical Microbiology Division, C606 GH, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242-1009, USA.
J Clin Microbiol. 2011 Feb;49(2):630-7. doi: 10.1128/JCM.02161-10. Epub 2010 Dec 15.
We tested 16,191 strains of Candida against posaconazole and voriconazole, using the CLSI M27-A3 broth microdilution (BMD) method (24-h incubation), in order to define wild-type (WT) populations and epidemiological cutoff values (ECVs). From 2001 to 2009, 8,619 isolates of Candida albicans, 2,415 isolates of C. glabrata, 2,278 isolates of C. parapsilosis, 1,895 isolates of C. tropicalis, 508 isolates of C. krusei, 205 isolates of C. lusitaniae, 177 isolates of C. guilliermondii, and 93 isolates of C. kefyr were obtained from over 100 centers worldwide. The modal MICs (μg/ml) for posaconazole and voriconazole, respectively, were as follows: for C. albicans, 0.016 and 0.007; for C. glabrata, 0.5 and 0.06; for C. parapsilosis, 0.06 and 0.007; for C. tropicalis, 0.03 and 0.015; for C. krusei, 0.25 and 0.12; for C. lusitaniae, 0.03 and 0.007; for C. guilliermondii, 0.12 and 0.03; and for C. kefyr, 0.06 and 0.007. The ECVs (μg/ml [% of isolates that had MICs equal to or less than the ECV]) for posaconazole and voriconazole, respectively, were as follows: 0.06 (98.5) and 0.03 (98.9) for C. albicans, 2 (96.2) and 0.5 (90.4%) for C. glabrata, 0.25 (99.3) and 0.12 (97.9) for C. parapsilosis, 0.12 (97.6) and 0.06 (97.2) for C. tropicalis, 0.5 (99.8) and 0.5 (99.4) for C. krusei, 0.12 (95.6) and 0.03 (96.6) for C. lusitaniae, 0.5 (98.9) and 0.25 (98.3) for C. guilliermondii, and 0.25 (100.0) and 0.015 (100.0) for C. kefyr. In the absence of clinical breakpoints (CBPs) for posaconazole, these WT distributions and ECVs will be useful in surveillance for emergence of reduced susceptibility to posaconazole among Candida spp. Whereas a CBP for susceptibility of ≤ 1 μg/ml has been established for voriconazole and all species of Candida, it is notable that ECVs for this agent range from 10- to >100-fold lower than the CBP, depending on the species of Candida. The CBP is inadequate in detecting the emergence of voriconazole resistance among most Candida species encountered clinically. The CBPs for voriconazole should be reassessed, with consideration for development of species-specific CBPs.
我们使用 CLSI M27-A3 肉汤微量稀释(BMD)法(24 小时孵育),对 16191 株念珠菌进行了泊沙康唑和伏立康唑的检测,以确定野生型(WT)种群和流行病学临界值(ECV)。2001 年至 2009 年,我们从全球 100 多个中心获得了 8619 株白色念珠菌、2415 株光滑念珠菌、2278 株近平滑念珠菌、1895 株热带念珠菌、508 株克柔念珠菌、205 株葡萄牙念珠菌、177 株季也蒙念珠菌和 93 株恺柔念珠菌。泊沙康唑和伏立康唑的模态 MIC(μg/ml)分别为:白色念珠菌 0.016 和 0.007;光滑念珠菌 0.5 和 0.06;近平滑念珠菌 0.06 和 0.007;热带念珠菌 0.03 和 0.015;克柔念珠菌 0.25 和 0.12;葡萄牙念珠菌 0.03 和 0.007;季也蒙念珠菌 0.12 和 0.03;恺柔念珠菌 0.06 和 0.007。泊沙康唑和伏立康唑的 ECV(μg/ml[等于或低于 ECV 的 MIC 的分离株百分比])分别为:白色念珠菌 0.06(98.5)和 0.03(98.9)、光滑念珠菌 2(96.2)和 0.5(90.4%)、近平滑念珠菌 0.25(99.3)和 0.12(97.9)、热带念珠菌 0.12(97.6)和 0.06(97.2)、克柔念珠菌 0.5(99.8)和 0.5(99.4)、葡萄牙念珠菌 0.12(95.6)和 0.03(96.6)、季也蒙念珠菌 0.5(98.9)和 0.25(98.3)、恺柔念珠菌 0.25(100.0)和 0.015(100.0)。在缺乏泊沙康唑临床折点(CBPs)的情况下,这些 WT 分布和 ECVs 将有助于监测念珠菌属中对泊沙康唑敏感性降低的情况。虽然已经为伏立康唑和所有念珠菌种建立了 ≤1μg/ml 的敏感性 CBPs,但值得注意的是,该药物的 ECV 范围从 10 倍到 >100 倍不等,具体取决于念珠菌种。CBPs 不足以检测到临床上大多数念珠菌种中伏立康唑耐药性的出现。应该重新评估伏立康唑的 CBPs,并考虑制定特定种的 CBPs。