Arendrup M C, Prakash Anupam, Meletiadis Joseph, Sharma Cheshta, Chowdhary Anuradha
Unit of Mycology, Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Antimicrob Agents Chemother. 2017 May 24;61(6). doi: 10.1128/AAC.00485-17. Print 2017 Jun.
is an emerging multidrug-resistant yeast. So far, all but two susceptibility testing studies have examined ≤50 isolates, mostly with the CLSI method. We investigated CLSI and EUCAST MICs for 123 isolates and eight antifungals and evaluated various methods for epidemiological cutoff (ECOFF) determinations. MICs (in milligrams per liter) were determined using CLSI method M27-A3, and the EUCAST E.Def 7.3. ANOVA analysis of variance with Bonferroni's multiple-comparison test and Pearson analysis were used on log MICs (significance at values of <0.05). The percent agreement (within ±0 to ±2 2-fold dilutions) between the methods was calculated. ECOFFs were determined visually, statistically (using the ECOFF Finder program and MicDat1.23 software with 95% to 99% endpoints), and via the derivatization method (dECOFFs). The CLSI and EUCAST MIC distributions were wide, with several peaks for all compounds except amphotericin B, suggesting possible acquired resistance. Modal MIC, geometric MIC, MIC, and MIC values were ≤1 2-fold dilutions apart, and no significant differences were found. The quantitative agreement was best for amphotericin B (80%/97% within ±1/±2 dilutions) and lowest for isavuconazole and anidulafungin (58%/76% to 75% within ±1/±2 dilutions). We found that 90.2%/100% of the isolates were amphotericin B susceptible based on CLSI/EUCAST methods, respectively (i.e., with MICs of ≤1 mg/liter), and 100%/97.6% were fluconazole nonsusceptible by CLSI/EUCAST (MICs > 2). The ECOFFs (in milligrams per liter) were similar across the three different methods for itraconazole (ranges for CLSI/EUCAST, 0.25 to 0.5/0.5 to 1), posaconazole (0.125/0.125 to 0.25), amphotericin B (0.25 to 0.5/1 to 2), micafungin (0.25 to 0.5), and anidulafungin (0.25 to 0.5/0.25 to 1). In contrast, the estimated ECOFFs were dependent on the method applied for voriconazole (1 to 32) and isavuconazole (0.125 to 4). CLSI and EUCAST MICs were remarkably similar and confirmed uniform fluconazole resistance and variable acquired resistance to the other agents.
是一种新出现的多重耐药酵母。到目前为止，除两项药敏试验研究外，其他所有研究检测的分离株均≤50株，大多采用临床和实验室标准协会（CLSI）方法。我们研究了123株分离株对8种抗真菌药物的CLSI和欧洲抗微生物药敏试验委员会（EUCAST）最低抑菌浓度（MIC），并评估了多种确定流行病学截断值（ECOFF）的方法。使用CLSI方法M27 - A3测定MIC（以毫克/升为单位），以及EUCAST E.Def 7.3。对log MIC值进行方差分析（ANOVA）及Bonferroni多重比较检验和Pearson分析（P值<0.05时有统计学意义）。计算两种方法之间的百分一致性（在±0至±2倍稀释范围内）。通过目视、统计学方法（使用ECOFF Finder程序和MicDat1.23软件，端点为95%至99%）以及衍生化方法（dECOFFs）确定ECOFF。CLSI和EUCAST的MIC分布较宽，除两性霉素B外，所有化合物均有多个峰值，提示可能存在获得性耐药。众数MIC、几何MIC、MIC₅₀和MIC₉₀值相差≤1个2倍稀释度，未发现显著差异。两性霉素B的定量一致性最佳（在±1/±2倍稀释范围内分别为80%/97%），而艾沙康唑和阿尼芬净的定量一致性最低（在±1/±2倍稀释范围内为58%/76%至75%）。我们发现，基于CLSI/EUCAST方法，分别有90.2%/100%的分离株对两性霉素B敏感（即MIC≤1毫克/升），而CLSI/EUCAST显示100%/97.6%的分离株对氟康唑不敏感（MIC>2）。伊曲康唑、泊沙康唑、两性霉素B、米卡芬净和阿尼芬净的ECOFF（以毫克/升为单位）在三种不同方法间相似（CLSI/EUCAST的范围分别为：伊曲康唑0.25至0.5/0.5至1；泊沙康唑0.125/0.125至0.25；两性霉素B 0.25至0.5/1至2；米卡芬净0.25至0.5；阿尼芬净0.25至0.5/0.25至1）。相比之下，伏立康唑（1至32）和艾沙康唑（0.125至4）的估计ECOFF取决于所应用的方法。CLSI和EUCAST的MIC非常相似，证实了氟康唑耐药的一致性以及对其他药物获得性耐药的变异性。
