Unit of Mycology, Statens Serum Institut, Copenhagen, Denmark; Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands; Clinical Microbiology Laboratory, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Clin Microbiol Infect. 2018 Nov;24(11):1200-1204. doi: 10.1016/j.cmi.2018.02.021. Epub 2018 Mar 2.
Rezafungin (CD101) is a new long-acting echinocandin allowing weekly dosing, currently undergoing phase-II clinical trials for invasive candidiasis. The aim of this study was to assess rezafungin's in vitro activity against the most frequent Candida species following the EUCAST methodology.
The susceptibility of 2018 clinical Candida isolates was determined at four European laboratories. In parallel, six control strains were repeatedly tested. Wild-type upper limits (WT-ULs), defined as the MIC value where the wild-type distribution ends, were determined following the principles for EUCAST ECOFF-setting.
The lowest rezafungin MICs (geometric MIC (GM-MIC), MIC range (mg/L)) were observed for C. albicans (0.016, 0.002-0.125) and the highest for C. parapsilosis (1.657, 0.063->4). MICs for the remaining species were in between these values (GM-MICs 0.048-0.055). Visual and statistical WT-ULs were identical for C. glabrata (0.125), C. krusei (0.125), C. parapsilosis (4), and C. tropicalis (0.25). If adopting these WT-ULs for classification into WT and non-WT populations, 1/413 C. glabrata, 1/402 C. krusei, 1/398 C. parapsilosis, and 1/402 C. tropicalis isolates were categorized as non-WT, all of which derived from Laboratory 1. For C. albicans unexplained laboratory variation was observed (WT-UL: 0.063-0.125 in Laboratories 1 and 2 versus 0.016 in Laboratories 3 and 4). A similar systematic difference was observed comparing the MICs for the three C. albicans QC strains, specifically, obtained in Laboratories 1and 2 with those in Laboratories 3 and 4.
Rezafungin displayed species-specific activity similar to other echinocandins. Interlaboratory variation was observed for the most susceptible species C. albicans clinical and QC strains, an observation that warrants further investigation.
雷萨凡辛(CD101)是一种新型的长效棘白菌素类药物,允许每周给药,目前正在进行侵袭性念珠菌病的 II 期临床试验。本研究的目的是按照 EUCAST 方法评估雷萨凡辛对最常见念珠菌种的体外活性。
在四个欧洲实验室测定 2018 年临床分离的念珠菌的药敏性。同时,对六株对照株进行了重复检测。根据 EUCAST ECOFF 设定的原则,确定野生型上限(WT-UL),定义为野生型分布结束时的 MIC 值。
最低的雷萨凡辛 MIC 值(几何 MIC(GM-MIC),MIC 范围(mg/L))观察到 C. albicans(0.016,0.002-0.125),最高的 C. parapsilosis(1.657,0.063->4)。其余种属的 MIC 值介于这些值之间(GM-MIC 值 0.048-0.055)。C. glabrata(0.125)、C. krusei(0.125)、C. parapsilosis(4)和 C. tropicalis(0.25)的视觉和统计 WT-UL 相同。如果采用这些 WT-UL 将其分类为 WT 和非 WT 群体,413 株 C. glabrata 中有 1 株/株、402 株 C. krusei 中有 1 株/株、398 株 C. parapsilosis 中有 1 株/株和 402 株 C. tropicalis 中有 1 株/株被归类为非 WT,所有这些都是从实验室 1 分离的。对 C. albicans 观察到不明原因的实验室变异(WT-UL:实验室 1 和 2 为 0.063-0.125,实验室 3 和 4 为 0.016)。在比较三种 C. albicans QC 株的 MIC 时,也观察到类似的系统差异,特别是在实验室 1 和 2 获得的 MIC 与实验室 3 和 4 获得的 MIC 相比。
雷萨凡辛对不同种属的念珠菌显示出特异性活性,类似于其他棘白菌素类药物。最敏感的种属 C. albicans 临床和 QC 株之间观察到了实验室间的变异,这一观察结果需要进一步研究。