Background: SCY-078 is a novel, oral and intravenous, triterpenoid class glucan synthase inhibitor under development for the treatment of fungal infections including invasive candidiasis. Early studies demonstrated superior in vitro activity of SCY-078 compared to echinocandins (ECH), caspofungin (CSP) and micafungin (MFG), against C. glabrata isolates with fks mutations. This study evaluated the in vitro antifungal activity of SCY-078 against recent clinical isolates and a collection of echinocandin-resistant (ECH-R) strains. Methods: A retrospective analysis was conducted from 3 independent studies with SCY-078 with isolates collected between 2013-2015 in two clinical centers (US and EU, N=275) and a subset of samples from the SENTRY Antimicrobial Surveillance Program Collection program in 2013 (N=307). The 3 studies also included a panel of isolates (N= 97) with genotypic, phenotypic (defined in CLSI M27-A4) or clinical ECH-R. Minimum inhibitory concentrations (MIC) were determined according to CLSI M27-A3. Resistance to SCY-078 was defined as an MIC 2-dilutions higher than the modal MIC. Comparator ECH varied across studies and consisted of MCF, CSP or anidulafungin (ANF). Results: Among these recently obtained clinical isolates, the most commonly observed spp were C. albicans (N=150) C. glabrata (N=98), C. parapsilosis (N=91), C. tropicalis (N=50) and C. krusei (N=48); MIC values obtained for SCY-078 against these spp. isolates are shown below. C. glabrata isolates represented the majority of ECH-R strains, 67/97 (69%), followed by C. albicans (10/97, 10%), C. parapsilosis (9/97, 9%), C. krusei (4/97, 4%) and C. tropicalis (3/97, 3%). SCY-078 was active against the majority of the C. glabrata ECH-R strains; 49/67 (73%). Similar results were observed among the remaining 30 ECH-R Candida spp isolates; SCY-078 remained active against 21/30 (70%) isolates tested. Conclusions: SCY-078 was shown to have excellent activity against recent clinical Candida isolates, including those with ECH resistance.
Full conference title:
- ASM Microbe 2nd (2017)