In Vitro Activity of E1210, a Novel Antifungal, against Clinically Important Yeasts and Molds

被引:161
作者
Miyazaki, Mamiko [1 ]
Horii, Takaaki [1 ]
Hata, Katsura [1 ]
Watanabe, Nao-aki [1 ]
Nakamoto, Kazutaka [2 ]
Tanaka, Keigo [1 ]
Shirotori, Syuji [2 ]
Murai, Norio [2 ]
Inoue, Satoshi [2 ]
Matsukura, Masayuki [2 ]
Abe, Shinya [3 ]
Yoshimatsu, Kentaro [4 ]
Asada, Makoto [4 ]
机构
[1] Eisai & Co Ltd, Next Generat Syst Core Funct Unit, Eisai Prod Creat Syst, Tsukuba, Ibaraki, Japan
[2] Eisai & Co Ltd, Oncol Prod Creat Unit, Eisai Prod Creat Syst, Tsukuba, Ibaraki, Japan
[3] Eisai & Co Ltd, Pharmaceut Sci & Technol Core Funct Unit, Eisai Prod Creat Syst, Tsukuba, Ibaraki, Japan
[4] Eisai & Co Ltd, Eisai Prod Creat Syst, Bunkyo Ku, Tokyo, Japan
关键词
TESTING SUSCEPTIBILITIES; MICRODILUTION METHOD; CANDIDA-ALBICANS; AMPHOTERICIN-B; EPIDEMIOLOGY; INFECTIONS; ASPERGILLUS; ITRACONAZOLE; THERAPY; AGENTS;
D O I
10.1128/AAC.00291-11
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
E1210 is a new antifungal compound with a novel mechanism of action and broad spectrum of antifungal activity. We investigated the in vitro antifungal activities of E1210 compared to those of fluconazole, itraconazole, voriconazole, amphotericin B, and micafungin against clinical fungal isolates. E1210 showed potent activities against most Candida spp. (MIC90 of <= 0.008 to 0.06 mu g/ml), except for Candida krusei (MICs of 2 to >32 mu g/ml). E1210 showed equally potent activities against fluconazole-resistant and fluconazole-susceptible Candida strains. E1210 also had potent activities against various filamentous fungi, including Aspergillus fumigatus (MIC90 of 0.13 mu g/ml). E1210 was also active against Fusarium solani and some black molds. Of note, E1210 showed the greatest activities against Pseudallescheria boydii (MICs of 0.03 to 0.13 mu g/ml), Scedosporium prolificans (MIC of 0.03 mu g/ml), and Paecilomyces lilacinus (MICs of 0.06 mu g/ml) among the compounds tested. The antifungal action of E1210 was fungistatic, but E1210 showed no trailing growth of Candida albicans, which has often been observed with fluconazole. In a cytotoxicity assay using human HK-2 cells, E1210 showed toxicity as low as that of fluconazole. Based on these results, E1210 is likely to be a promising antifungal agent for the treatment of invasive fungal infections.
引用
收藏
页码:4652 / 4658
页数:7
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