In vitro activity of a new oral triazole, BMS-207147 (ER-30346)
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.
Fung-Tomc
J C
JC
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA. joanvc.vfung-tomc@ccmail.bms.com
Huczko
E
E
Minassian
B
B
Bonner
D P
DP
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D003454:Cryptococcus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D013844:Thiazoles / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D000935:Antifungal Agents; D013844:Thiazoles; D014230:Triazoles; D000666:Amphotericin B; C104066:ER 30346