Background:

Isavuconazole (BAL-4815) is a triazole prodrug with antifungal activity against yeasts, molds, and dimorphic fungi. Isavuconazole inhibits ergosterol biosynthesis and results in the disruption of fungal membrane structure and function. Isavuconazole is a moderate inhibitor of CYP3A4.

Isavuconazole (BAL-4815) shows good activity against all Candida spp., with active MIC50 of 0.004 mg/L. The MIC50s/MIC90s range from 0.002/0.004 mg/L for C. albicans to 0.25/0.5 mg/L for C. glabrata[1]. Isavuconazole has potent in vitro activity against most common Aspergillus species, Purpureocillium lilacinum, and Scedosporium apiospermum[2]. Isavuconazole shows potent activity against molds, yeasts, and dimorphic fungi. Rhizopus isolates have MIC values to isavuconazole as low as 0.12 μg/mL with others as high as 32 μg/mL[3]. In the study of pharmacokinetics and pharmacodynamics of isavuconazole against the GFP transformant, F/11628, NIH 4215, and F/16216, the modal MICs of isavuconazole are 1, 8, 1, 4 mg/L, respectively[4].

参考文献:
[1]. Seifert H, et al. In vitro activities of isavuconazole and other antifungal agents against Candida bloodstream isolates. Antimicrob Agents Chemother. 2007 May;51(5):1818-21.
[2]. Steinmann J, et al. In Vitro Activity of Isavuconazole against Rasamsonia Species. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6890-6891.
[3]. Donnelley MA, et al. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections. Infect Drug Resist. 2016 Jun 2;9:79-86.
[4]. Box H, et al. Pharmacodynamics of Isavuconazole in a Dynamic In Vitro Model of Invasive Pulmonary Aspergillosis. Antimicrob Agents Chemother. 2015 Oct 26;60(1):278-87.