Chugai Pharmaceutical Co. Ltd., Kamakura Research Laboratories, 200 Kajiwara Kamakura, Kanagawa 247-8530, Japan.
Int J Antimicrob Agents. 2010 Oct;36(4):324-31. doi: 10.1016/j.ijantimicag.2010.06.003. Epub 2010 Jul 31.
The in vitro susceptibilities of 140 laboratory reference strains of fungi, including type strains, and 165 clinical yeast isolates from Japan towards isavuconazole compared with fluconazole (FLC), itraconazole (ITC), voriconazole and amphotericin B were measured. Broth microdilution methods based on Clinical and Laboratory Standards Institute (CLSI) methods were used for yeasts, and RPMI-MOPS medium semi-solidified with 0.2% low-melting-point agarose based on CLSI guidelines was used for moulds. The range of isavuconazole minimum inhibitory concentrations (MICs) was 0.0004-0.21 mg/L for Candida albicans, 0.0036-0.4 mg/L for Candida glabrata, 0.023-0.058 mg/L for Candida krusei, 0.0026-0.032 mg/L for Cryptococcus neoformans, 0.1-0.39mg/L for Aspergillus fumigatus and 0.2-0.39 mg/L for Aspergillus terreus. Isavuconazole was as active as ITC against the dimorphic true pathogenic fungi, with a range of MICs from <0.0004 mg/L to 0.0063 mg/L for Blastomyces dermatitidis and Histoplasma capsulatum. It was also active against uncommon dematiaceous fungi such as Exophiala spp. and Phialophora spp. as well as against dermatophytic species. Isavuconazole showed very good in vitro antifungal activity with a broad spectrum, including against FLC-resistant Candida spp., Aspergillus spp. and uncommon opportunistic fungal species. This is the first report of the in vitro susceptibility of Japanese clinical yeast isolates to isavuconazole. No cross-resistance was found to isavuconazole amongst FLC-resistant strains.
对 140 株实验室参考真菌菌株,包括模式株,和 165 株日本临床酵母分离株进行了体外药敏试验,比较了伊曲康唑(ITC)、伏立康唑、两性霉素 B 和伊沙康唑对这些菌株的敏感性。采用基于临床和实验室标准化协会(CLSI)方法的肉汤微量稀释法对酵母菌进行检测,采用 RPMI-MOPS 培养基,其中含有 0.2%低熔点琼脂糖,按照 CLSI 指南进行半固体化,用于对霉菌进行检测。白念珠菌的伊沙康唑最小抑菌浓度(MIC)范围为 0.0004-0.21 毫克/升,光滑念珠菌为 0.0036-0.4 毫克/升,克柔念珠菌为 0.023-0.058 毫克/升,新型隐球菌为 0.0026-0.032 毫克/升,烟曲霉为 0.1-0.39 毫克/升,土曲霉为 0.2-0.39 毫克/升。伊沙康唑对二相致病真菌的活性与 ITC 相当,MIC 范围为 0.0004-0.0063 毫克/升,用于皮炎芽生菌和荚膜组织胞浆菌。它还对罕见的暗色真菌,如外瓶霉属和帚霉属,以及皮肤真菌具有活性。伊沙康唑具有广泛的体外抗真菌活性,包括对氟康唑耐药的念珠菌属、曲霉属和罕见的机会性真菌物种。这是首次报道日本临床酵母分离株对伊沙康唑的体外敏感性。在氟康唑耐药株中未发现对伊沙康唑的交叉耐药性。