Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs
Abstract
Although antifungal drug resistance in the human fungal pathogen Cryptococcus neoformans is relatively uncommon, fluconazole-resistant strains are problematic for preemptive treatment of cryptococcal antigenemia or during cryptococcal meningitis consolidation therapy. We analyzed activity of the experimental antifungal VT-1129 on 51 clinical Cryptococcus neoformans isolates previously screened for fluconazole resistance; with an emphasis on fluconazole dose-dependent (MIC 16-32 μg/ml) or resistant (MIC ≥ 64 μg/ml) isolates. Overall, the VT-1129 geometric mean MIC was 0.027 μg/ml. The VT-1129 MIC50 was 0.05 μg/ml and 0.25 μg/ml for dose-dependent (n = 27) and resistant isolates (n = 6), respectively. These data suggest VT-1129 shows potential for use against fluconazole-resistant Cryptococcus.
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VT-1129 is an oral tetrazole with robust in vitro and in vivo efficacy against C. neoformans and C. gattii, maintaining activity (mean MIC 0.027 μg/mL) against fluconazole-resistant or dose-dependent C. neoformans isolates.
“Preclinical studies have demonstrated robust in vitro and in vivo efficacy against C. neoformans and C. gattii, notably maintaining activity (mean MIC 0.027 μg/mL) against fluconazole-resistant or dose-dependent C. neoformans isolates (Fig. 1) [92–94].”
From Investigational Agents for the Treatment of Resistant Yeasts and Molds (2021) · cites this paper as [93]
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References 16 · Cited by 24
- Authors
- Nielsen, K., Vedula, P., Smith, K. D., Meya, D. B., Garvey, E. P., Hoekstra, W. J., Schotzinger, R. J., & Boulware, D. R.
- Affiliations
- University of Minnesota (US)
- Infectious Diseases Institute (UG)
- Viamet Pharmaceuticals (United States) (US)
- Corresponding author
- Nielsen, Kirsten
- Venue
- Medical Mycology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-09-24
- Volume
- 55
- Issue
- 4
- Pages
- myw089
- ISSN
- 0268-1218 (ISSN-L)
- 1369-3786
- 1460-2709
- OpenAlex
- W2521669060
- Cited by
- 24
- References
- 16
- Citations by year
- 2022: 2 · 2021: 9 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 1
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medical Mycology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- Cryptococcus neoformans, fluconazole resistance, antifungal susceptibility, minimum inhibitory concentration, dose-dependent resistance, cryptococcal meningitis, cryptococcal antigenemia, antifungal resistance
- MeSH terms
- Antifungal Agents, Cryptococcosis, Cryptococcus neoformans, Humans, Microbial Sensitivity Tests, Pyridines, Tetrazoles, Fluconazole, Drug Resistance, Fungal
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