Fungal CYP51 Inhibitors VT-1161 and VT-1129 Exhibit Strong <i>In Vitro</i> Activity against Candida glabrata and C. krusei Isolates Clinically Resistant to Azole and Echinocandin Antifungal Compounds

Abstract

The <i>in vitro</i> activities of fungal CYP51 inhibitors VT-1161 and VT-1129 were determined for <i>Candida glabrata</i> (<i>n</i> = 34) and <i>C. krusei</i> (<i>n</i> = 50). <i>C. glabrata</i> isolates were screened for FKS gene mutations. All isolates were resistant clinically and/or <i>in vitro</i> to at least one standard antifungal compound. VT-1161 and VT-1129 MICs for all isolates were at least 5-fold below achievable human plasma levels for VT-1161. VT-1161 and VT-1129 are promising for the treatment of resistant <i>C. glabrata</i> and <i>C. krusei</i> infections.