title: In vitro activity of isavuconazole against 140 reference fungal strains and 165 clinically isolated yeasts from Japan.
abstract: 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.
authors.affiliation: Chugai Pharmaceutical Co. Ltd., Kamakura Research Laboratories, 200 Kajiwara Kamakura, Kanagawa 247-8530, Japan. yamazakitsk@chugai-pharm.co.jp
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Jun
authors.initials: J
authors.lastname: Ohwada
authors.forename: Masao
authors.initials: M
authors.lastname: Tsukazaki
authors.forename: Isao
authors.initials: I
authors.lastname: Umeda
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shimma
authors.forename: Malcolm G P
authors.initials: MG
authors.lastname: Page
authors.forename: Mikio
authors.initials: M
authors.lastname: Arisawa
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D007564:Japan; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000592:standards; D009181:Mycoses / Q000382:microbiology*; D009570:Nitriles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012015:Reference Standards; D014230:Triazoles / Q000494:pharmacology*; D015003:Yeasts / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D009570:Nitriles; D011725:Pyridines; D014230:Triazoles; C508735:isavuconazole; D000666:Amphotericin B