Oral glucan synthase inhibitor SCY-078 is effective in an experimental murine model of invasive candidiasis caused by WT and echinocandin-resistant Candida glabrata
Open accessAbstract
Background: Echinocandins are recommended as first-line therapy against Candida glabrata infections, although increased resistance to this class has been reported worldwide and they are currently only available for parenteral administration. SCY-078 is an investigational glucan synthase inhibitor that is orally available. Objectives: To evaluate the in vivo efficacy of SCY-078 in an experimental model of invasive candidiasis due to WT and echinocandin-resistant C. glabrata isolates. Methods: Neutropenic ICR mice were inoculated intravenously with a WT isolate (SCY-078 and caspofungin MICs 0.25 and 0.125 mg/L, respectively) or an echinocandin-resistant isolate (SCY-078 and caspofungin MICs 1 and 0.5 mg/L, respectively). Treatment with placebo, SCY-078 (8, 30 or 40 mg/kg orally every 12 h) or caspofungin (1 mg/kg by intraperitoneal injection once daily) began 24 h later. Kidney fungal burden was measured on day 8 post-inoculation. Results: Significant reductions in kidney fungal burden were observed with 30 mg/kg SCY-078 against both isolates and with the 40 mg/kg dose against the echinocandin-resistant isolate. These results were supported by SCY-078 plasma concentration data at the higher doses, where levels above the MICs for both isolates were observed 12 h after the last oral dose. Reductions in fungal burden were also observed with caspofungin against the WT isolate, but not against the resistant isolate. Conclusions: SCY-078 demonstrated in vivo efficacy against infections caused by both WT and echinocandin-resistant C. glabrata isolates in this experimental model. This orally available glucan synthase inhibitor has potential as a therapy against echinocandin-resistant C. glabrata infections.
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SCY-078 appears to be active against echinocandin-resistant and azole-resistant Candida strains, including C. auris.
“Importantly, SCY-078 appears to be active against echinocandin-resistant and azole-resistant Candida strains, including C. auris [111,112,113].”
From Treatment of Invasive Candidiasis: A Narrative Review (2018) · cites this paper as [113]
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- Authors
- Wiederhold, N. P., Najvar, L. K., Jaramillo, R., Olivo, M., Pizzini, J., Catano, G., & Patterson, T. F.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Wiederhold, Nathan P
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-11-21
- Volume
- 73
- Issue
- 2
- Pages
- 448-451
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- PMC
- PMC5890676
- OpenAlex
- W2770721343
- Cited by
- 43
- References
- 21
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 14 · 2020: 6 · 2019: 7 · 2018: 2
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Antimicrobial Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- invasive candidiasis, Candida glabrata, echinocandin resistance, caspofungin, oral antifungal therapy, neutropenic mice, kidney fungal burden, antifungal susceptibility
- MeSH terms
- Caspofungin, Administration, Oral, Animals, Antifungal Agents, Disease Models, Animal, Glycosides, Injections, Intraperitoneal, Kidney, Male, Mice, Inbred ICR, Placebos, Triterpenes, Colony Count, Microbial, Treatment Outcome, Candida glabrata, Candidiasis, Invasive
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