Fung-Tomc J C, Huczko E, Minassian B, Bonner D P
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
Antimicrob Agents Chemother. 1998 Feb;42(2):313-8. doi: 10.1128/AAC.42.2.313.
The antifungal activity of BMS-207147 (also known as ER-30346) was compared to those of itraconazole and fluconazole against 250 strains of fungi representing 44 fungal species. MICs were determined by using the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth macrodilution method for yeasts, which was modified for filamentous fungi. BMS-207147 was about two- to fourfold more potent than itraconazole and about 40-fold more active than fluconazole against yeasts. With the NCCLS-recommended resistant MIC breakpoints of > or = 1 microg/ml for itraconazole and of > or = 64 microg/ml for fluconazole against Candida spp., itraconazole and fluconazole were inactive against strains of Candida krusei and Candida tropicalis. In contrast, all but 9 (all C. tropicalis) of the 116 Candida strains tested had BMS-207147 MICs of < 1 microg/ml. The three triazoles were active against about half of the Candida glabrata strains and against all of the Cryptococcus neoformans strains tested. The three triazoles were fungistatic to most yeast species, except for BMS-207147 and itraconazole, which were fungicidal to cryptococci. BMS-207147 and itraconazole were inhibitory to most aspergilli, and against half of the isolates, the activity was cidal. BMS-207147 and itraconazole were active, though not cidal, against most hyaline Hyphomycetes (with the exception of Fusarium spp. and Pseudallescheria boydii), dermatophytes, and the dematiaceous fungi and inactive against Sporothrix schenckii and zygomycetes. Fluconazole, on the other hand, was inactive against most filamentous fungi with the exception of dermatophytes other than Microsporum gypseum. Thus, the spectrum and potency of BMS-207147 indicate that it should be a candidate for clinical development.
将BMS-207147（也称为ER-30346）的抗真菌活性与伊曲康唑和氟康唑针对代表44种真菌的250株真菌进行了比较。采用美国国家临床实验室标准委员会（NCCLS）推荐的用于酵母的肉汤稀释法测定最低抑菌浓度（MIC），该方法针对丝状真菌进行了修改。BMS-207147对酵母的效力比伊曲康唑高约两到四倍，比氟康唑高约40倍。根据NCCLS推荐的针对念珠菌属的伊曲康唑耐药MIC临界值≥1μg/ml和氟康唑耐药MIC临界值≥64μg/ml，伊曲康唑和氟康唑对克鲁斯念珠菌和热带念珠菌菌株无活性。相比之下，在测试的116株念珠菌菌株中，除9株（均为热带念珠菌）外，其余所有菌株的BMS-207147 MIC均<1μg/ml。这三种三唑类药物对约一半的光滑念珠菌菌株和所有测试的新生隐球菌菌株有活性。这三种三唑类药物对大多数酵母菌种具有抑菌作用，但BMS-207147和伊曲康唑对隐球菌具有杀菌作用。BMS-207147和伊曲康唑对大多数曲霉菌有抑制作用，对一半的分离株有杀菌活性。BMS-207147和伊曲康唑对大多数透明丝孢菌（除镰刀菌属和博伊德假性霉样真菌外）、皮肤癣菌和暗色真菌有活性，对申克孢子丝菌和接合菌无活性。另一方面，氟康唑除对石膏样小孢子菌以外的皮肤癣菌外，对大多数丝状真菌无活性。因此，BMS-207147的抗菌谱和效力表明它应是临床开发的候选药物。
