4.7 Article

The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp.

Journal

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 72, Issue 7, Pages 1969-1976

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/jac/dkx010

Keywords

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Funding

  1. SCYNEXIS Inc., Durham, NC, USA
  2. Fondo de Investigacion Sanitaria (FIS, Instituto de Salud Carlos III, Madrid, Spain) [PI14/00740]
  3. Fondo de Investigacion Sanitaria (FIS, Plan Nacional de I+D+I, European Regional Development Fund (FEDER) 'A way of making Europe')
  4. FIS [PI14/00740, CPI15/00115, CPII15/00006]

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Objectives: We studied the antifungal activity of SCY-078 (an orally bioavailable 1,3-beta-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.

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