In vitro studies of a new antifungal triazole, D0870, against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts

In vitro studies of a new antifungal triazole, D0870, against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts
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DOI:
10.1128/aac.37.10.2126
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发表时间:
1993-10
影响因子:
4.9
通讯作者:
T. Peng;J. Galgiani
T. Peng;J. Galgiani
中科院分区:
医学2区
文献类型:
--
作者:
T. Peng;J. Galgiani

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在美国国家临床实验室标准委员会(NCCLS)提出的肉汤大量稀释法中,研究了不同的测定条件对D0870对7种真菌的活性的影响。多变量分析表明,终点定义、起始接种量、培养基组分、缓冲液类型和培养时间对结果有显著影响,而不是pH或温度。将接种量从10(2)个酵母细胞/毫升增加到10(5)个酵母细胞/毫升,所有菌株的最低抑菌浓度都提高到75,000倍。当终点对应于目测确定的浊度(MIC90)减少90%时,这种影响最大,当视觉终点(MIC80)抑制80%时,这种效果不那么显著,而当通过分光光度计(IC1/2)测量终点为50%时,几乎没有这种影响。由于培养基组分的不同可归因于抗生素3和RPMI和酵母氮基培养基表现几乎相同。在NCCLS文件M27-P(酵母菌肉汤稀释抗真菌敏感性试验的参考方法;建议的标准,1992年)规定的标准化条件下,79株(每种5~25株)对白色念珠菌和新生隐球菌的MIC80值分别为0.0037和0.0075微克/毫升。而克鲁斯假丝酵母菌和光滑念珠菌的MIC80中位数为1.0微克/毫升。我们的研究表明,致病酵母对D0870比其他致病酵母更敏感。
We investigated the effects of various assay conditions on the activity of D0870 against seven species of fungi in the broth macrodilution testing procedure proposed by the National Committee for Clinical Laboratory Standards (NCCLS). Multivariate analysis demonstrated that endpoint definition, starting inoculum size, medium composition, type of buffer, and length of incubation, but not pH or temperature, had significant effects on results. Increasing the inoculum from 10(2) to 10(5) yeast cells/ml raised the MICs for all isolates up to > 75,000 fold. This effect was greatest when endpoints corresponded to a 90% reduction in visually determined turbidity (MIC90), was less prominent with an 80% inhibition visual endpoint (MIC80), and was nearly absent with a 50% endpoint measured by a spectrophotometer (IC1/2). Differences due to medium composition were attributable to antibiotic medium 3 with RPMI and yeast nitrogen base media performing nearly identically. Under standardized conditions as specified in NCCLS document M27-P (Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Proposed Standard, 1992), 79 strains (5 to 25 strains for each species) demonstrated median MIC80s of 0.0037 and 0.0075 microgram/ml for Candida albicans and Cryptococcus neoformans, respectively. In contrast, Candida krusei and Torulopsis glabrata had a median MIC80 of 1.0 microgram/ml. Our studies indicate that the pathogenic yeasts C. albicans and C. neoformans are more susceptible to D0870 than other pathogenic yeasts.