Evaluation of Synergistic Activity of Isavuconazole or Voriconazole plus Anidulafungin and the Occurrence and Genetic Characterization of Candida auris Detected in a Surveillance Program
Evaluation of Synergistic Activity of Isavuconazole or Voriconazole plus Anidulafungin and the Occurrence and Genetic Characterization of Candida auris Detected in a Surveillance Program
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DOI：
10.1128/aac.02031-20
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发表时间：
2021-04-01
影响因子：
4.9
通讯作者：
Castanheira, Mariana
中科院分区：
文献类型：
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作者：
Pfaller, Michael A.;Messer, Shawn A.;Castanheira, Mariana
将2006年至2019年期间SENTRY抗菌药物监测项目中的15株耳念珠菌分离株与来自其他保藏中心的21株分离株合并，使用棋盘法评价抗真菌药敏性和对阿尼芬净+伏立康唑或艾沙康唑的协同作用。监测菌株的遗传相关性和耐药机制进行了分析。应用暂定统计流行病学临界值和疾病控制中心暂定折点，32/36株分离株对氟康唑耐药，5/36株对阿替霉素B耐药，5/36株对阿尼芬净为非野生型（NWT），3/36株对米卡芬净为NWT，1/36株和10/36株分别对艾沙康唑和伏立康唑为NWT。其中，10株为多重耐药，这意味着这些菌株对2种抗真菌药物耐药。在阿尼芬净+伏立康唑联合治疗的分离株中，分别有5/36和22/36株出现协同作用或部分协同作用，在阿尼芬净+艾沙康唑联合治疗的分离株中，分别有11/36和19/36株出现协同作用或部分协同作用。对15株SENTRY分离株的多位点序列类型（MLST）分析表明，来自美国的分离株与来自拉丁美洲（巴拿马和哥伦比亚）和德国的分离株在遗传上相关，但不同。单核苷酸多态性（SNP）分析显示，15个SENTRY分离株属于所描述的国际分支，并具有相关的Erg 11变异，包括11个分离株显示K143 R，1个显示F126 L，1个显示Y501 H变异，氟康唑MIC结果>= 64 mg/L。在显示氟康唑MIC值为4和16 mg/L的两个分离株中未观察到耐药机制。与阿尼芬净联合伏立康唑相比，艾沙康唑对显示耐药表型的耳念珠菌临床分离株显示出活性和更大的协同作用。
A total of 15 Candida auris isolates from the SENTRY antimicrobial surveillance program between 2006 and 2019 were combined with 21 isolates from other collections for the evaluation of antifungal susceptibility and synergy against anidulafungin plus voriconazole or isavuconazole using the checkerboard method. Surveillance isolates were analyzed for genetic relatedness and resistance mechanisms. Applying the tentative statistical epidemiological cutoff values and the Centers for Disease Control tentative breakpoints, 32/36 isolates were resistant to fluconazole, 5/36 were resistant to amphotericin B, 5/36 were non-wild-type (NWT) to anidulafungin, 3/36 were NWT to micafungin, and 1/36 and 10/36 were NWT to isavuconazole and voriconazole, respectively. Of these, 10 isolates were multidrug resistant, which means that these isolates were resistant to 2 antifungal classes. Synergy or partial synergy was noted in 5/36 and 22/36, respectively, of the isolates with the combination of anidulafungin plus voriconazole, and 11/36 and 19/36 isolates, respectively, for the combination of anidulafungin plus isavuconazole. Multilocus sequence type (MLST) analysis of the 15 SENTRY isolates demonstrated that the isolates from the US were genetically related to, but different from, isolates from Latin America (Panama and Colombia) and Germany. Single nucleotide polymorphism (SNP) analysis showed that the 15 SENTRY isolates belonged to the described international clades and had associated Erg11 alterations, including 11 isolates displaying K143R, one displaying F126L, and one displaying Y501H alterations and a fluconazole MIC result of >= 64 mg/liter. Resistance mechanisms were not observed in the two isolates displaying fluconazole MIC values at 4 and 16 mg/liter. Isavuconazole displayed activity and greater synergy when tested with anidulafungin than seen with anidulafungin plus voriconazole against the C auris clinical isolates that displayed resistance phenotypes.