VCU Medical Center, Richmond, Virginia, USA
University of Adelaide, Adelaide, Australia.
Antimicrob Agents Chemother. 2018 Mar 27;62(4). doi: 10.1128/AAC.01916-17. Print 2018 Apr.
Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known mutations) and mutant isolates were as follows: by the CLSI method, 2,223 and 274, respectively; by the EUCAST method, 556 and 52, respectively; and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 μg/ml for the CLSI method and 0.25 μg/ml for the EUCAST method and Etest; NRI ECVs, 0.5 μg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 μg/ml. The tentative ECOFFinder ECV with SYO was 0.06 μg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 μg/ml (CLSI, EUCAST, Etest) or 0.06 μg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and mutants when up to 11.6% of the estimated wild-type population includes mutants.
估算流行病学截断终点 (ECV/ECOFFS) 可能会受到突变株和非突变株 MIC 重叠的阻碍（分别为携带或不携带突变的菌株）。从 26 个实验室（澳大利亚、加拿大、欧洲、印度、南美和北美以及中国台湾地区）和已发表的研究中收集了棘白菌素种复合体的泊沙康唑 MIC 分布。符合 CLSI 标准的分布被汇总在一起，并估算了 ECV。使用三种敏感性测试方法（CLSI、EUCAST 和 Etest 方法）检查了三种 ECV 分析技术（ECOFFinder、归一化耐药解释 [NRI]、衍生化方法）对包括突变株 MIC 的敏感性。非突变体分离株（无已知 突变的分离株）和突变体 分离株的泊沙康唑 MIC 总数如下：CLSI 方法分别为 2,223 和 274；EUCAST 方法分别为 556 和 52；Etest 方法分别为 1,365 和 29。用 Sensititre YeastOne 系统 (SYO) 评估了 381 株未知突变状态的分离株的 MIC。我们观察到非突变体和 突变体之间的泊沙康唑 MIC 存在重叠。在通常选择的模型野生型种群的百分比（97.5%）下，当合并非突变和突变分布的 MIC 时，几乎所有的 ECV 都保持不变：ECOFFinder ECV，CLSI 方法为 0.5 μg/ml，EUCAST 方法和 Etest 为 0.25 μg/ml；NRI ECV，所有三种方法均为 0.5 μg/ml。然而，CLSI 方法中 97.5%的非突变体群体的 ECOFFinder ECV 为 0.25 μg/ml。用 SYO 得出的暂定 ECOFFinder ECV 为 0.06 μg/ml（来自 8 个实验室中的 3 个的数据）。衍生化 ECV 无论是否包含突变，均为 0.25 μg/ml（CLSI、EUCAST、Etest）或 0.06 μg/ml（SYO）。当估计的野生型群体中多达 11.6%包括突变体时，ECV 分析技术似乎不会受到假定野生型分离株和 突变株之间重叠的影响。
