Differential Activity of the Oral Glucan Synthase Inhibitor SCY-078 against Wild-Type and Echinocandin-Resistant Strains of Candida Species.

Abstract

SCY-078 (formerly MK-3118) is a novel orally active inhibitor of fungal β-(1,3)-glucan synthase (GS). SCY-078 is a derivative of enfumafungin and is structurally distinct from the echinocandin class of antifungal agents. We evaluated the in vitro activity of this compound against wild-type (WT) and echinocandin-resistant isolates containing mutations in the FKS genes of Candida spp. Against 36 Candida spp. FKS mutants tested, 30 (83.3%) were non-WT to 1 or more echinocandins, and only 9 (25.0%) were non-WT (MIC, >WT-upper limit) to SCY-078. Among C. glabrata isolates carrying FKS alterations, 84.0% were non-WT to the echinocandins versus only 24.0% for SCY-078. In contrast to the echinocandin comparators, the activity of SCY-078 was minimally affected by the presence of FKS mutations, suggesting that this agent is useful in the treatment of Candida infections due to echinocandin-resistant strains.

• Authors: Michael A Pfaller, Shawn A Messer, Paul R Rhomberg, Katyna Borroto-Esoda, Mariana Castanheira
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 61 Issue 8 (08 2017) ISSN: 1098-6596 [Electronic] United States
• PMID: 28533234 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 American Society for Microbiology.

Chemical References

• Antifungal Agents
• Echinocandins
• Glycosides
• Triterpenes
• enfumafungin
• ibrexafungerp
• Glucosyltransferases
• glucan synthase

Topics

• Administration, Oral
• Antifungal Agents (pharmacology)
• Candida (drug effects, genetics)
• Candida glabrata (drug effects, genetics)
• Candidiasis (drug therapy, microbiology)
• Drug Resistance, Fungal
• Echinocandins (pharmacology)
• Glucosyltransferases (antagonists & inhibitors)
• Glycosides (pharmacology)
• Microbial Sensitivity Tests
• Mutation
• Triterpenes (pharmacology)