Assessment of the In Vitro Antifungal Activity of SCY-078 Against a Collection of C. parapsilosis Clinical Isolates. (4th October 2017) - Barat, Stephen
Abstract: Background: Global rates of candidemia caused by C. parapsilosis are increasing with differences detected between neonates and adult patients (50% vs. 12%, respectively) and across geographic regions (5% vs. 25% in Iceland and Spain, respectively). SCY-078 is a novel, oral and intravenous, triterpenoid glucan synthase inhibitor under development for the treatment of invasive candidiasis. This study evaluated the in vitro antifungal activity of SCY-078 against a collection of clinical C. parapsilosis isolates. Methods: Retrospective analysis of data from 7 independent studies evaluating the activity of SCY-078 is presented. Data were available for 206 C. parapsilosis isolates collected between 2008 and 2015 in the US and EU. The collection included 186 wild-type isolates as well as 14 azole-resistant, and 6 echinocandin-resistant isolates. Minimum inhibitory concentrations (MIC) were determined according to the CLSI M27-A3 and EUCAST E.DEF 7.3 guidelines. Comparator compounds varied across studies and included fluconazole, micafungin (MCF), caspofungin (CSP), and anidulafungin (ANI). MIC50 and MIC90 values were defined as the concentrations inhibiting growth of 50% and 90% of isolates, respectively. Echinocandin and azole resistance were determined based on CLSI M27-A4 guidelines. Results: The MIC50 values obtained for SCY-078 against the wild-type C. parapsilosis isolates across the 7 studies ranged from 0.25 to 1 μg/mL and the MIC90 values ranged from 0.25 -2 µg/mL. Among the echinocandins, MIC90 values ranged from 0.5 to 2 µg/mL (CSP), 1 to 4 µg/mL (MCF) and 2 to 4 µg/mL (ANI). SCY-078 was active against the 14 azole-resistant isolates (MIC ranging from 0.25 to 2 µg/mL). Similar activity was observed across the 6 echinocandin-resistant isolates with MIC values for SCY-078 ranging from 0.25 to 1 µg/mL. Among the 4 most recent studies in the US and EU (2013–2015) C. parapsilosis isolates represented 14 – 20% of the Candida isolates; rates were similar in the EU and US. Conclusion: SCY-078 demonstrated potent activity against C. parapsilosis clinical isolates. Notably, SCY-078 was effective against all the echinocandin and azole resistant C. parapsilosis isolates tested. Disclosures: S. Barat, Scynexis, Inc: Employee, Salary; D. Angulo, Scynexis, Inc.: Employee, Salary; K. Borroto-Esoda, Scynexis Inc.: Consultant, Consulting fee; M. Ghannoum, Scynexis, Inc.: Consultant, Investigator and Scientific Advisor, Consulting fee, Research grant and Research support