The Novel Oral Glucan Synthase Inhibitor SCY-078 Shows in Vitro Activity Against Sessile and Planktonic Candida SPP

J Antimicrob Chemother. 2017 Jul 1;72(7):1969-1976. doi: 10.1093/jac/dkx010.

Abstract

Objectives: We studied the antifungal activity of SCY-078 (an orally bioavailable 1,3-β -d- glucan synthesis inhibitor), micafungin and fluconazole against the planktonic and sessile forms of 178 Candida and non- Candida isolates causing fungaemia in patients recently admitted to a large European hospital.

Methods: The in vitro activity of SCY-078, micafungin and fluconazole against the planktonic form of the isolates was assessed using EUCAST EDef 7.3 and CLSI M27-A3. Antibiofilm activity was assessed using the XTT reduction assay.

Results: SCY-078 and micafungin showed potent in vitro activity against Candida and non- Candida isolates. The in vitro activity of both drugs was similar, but SYC-078 displayed significantly lower MIC values than micafungin against Candida parapsilosis and non- Candida isolates, whereas micafungin displayed significantly lower MIC values for the remaining species ( P <0.001). In contrast, SCY-078 and micafungin showed essentially the same activity against the biofilms with the exception of Candida glabrata , in which the micafungin sessile MIC values were significantly lower ( P <0.001). These observations were confirmed by assessing biofilm structure by scanning electron microscopy after antifungal treatment.

Conclusions: Our study showed that the high in vitro activity of SCY-078 against invasive Candida isolates in both sessile and planktonic forms is comparable to that of micafungin.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Biofilms / drug effects
  • Candida / drug effects*
  • Candida / isolation & purification
  • Candida / physiology
  • Candida albicans / drug effects
  • Candida glabrata / drug effects
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Candidiasis, Invasive / drug therapy
  • Candidiasis, Invasive / microbiology
  • Echinocandins / pharmacology
  • Glucosyltransferases / antagonists & inhibitors*
  • Glycosides / pharmacology*
  • Humans
  • Lipopeptides / pharmacology
  • Micafungin
  • Microbial Sensitivity Tests
  • Triterpenes / pharmacology*

Substances

  • Antifungal Agents
  • Echinocandins
  • Glycosides
  • Lipopeptides
  • MK-3118
  • Triterpenes
  • Glucosyltransferases
  • glucan synthase
  • Micafungin

Supplementary concepts

  • Systemic candidiasis