AI Article Synopsis
- Candida albicans is a leading fungal pathogen causing chronic infections, especially in patients with certain immune deficiencies, prompting the need for new antifungal therapies due to rising azole resistance.
- The study tested the effectiveness of new drugs VT-1161 and VT-1129 against both azole-susceptible and azole-resistant strains of C. albicans using clinical isolates and a mouse model.
- Results showed that both drugs had strong in vitro activity against most strains, with VT-1161 proving particularly effective in clearing infections in a mouse model, even with resistant strains.
Article Abstract
Background: Candida albicans, the most common human fungal pathogen, causes chronic mucosal infections in patients with inborn errors of IL-17 immunity that rely heavily on chronic, often lifelong, azole antifungal agents for treatment. However, a rise in azole resistance has predicated a need for developing new antifungal drugs.
Objectives: To test the in vitro and in vivo efficacy of VT-1161 and VT-1129 in the treatment of oropharyngeal candidiasis with azole-susceptible or -resistant C. albicans strains.
Methods: MICs of VT-1161, VT-1129 and nine licensed antifungal drugs were determined for 31 Candida clinical isolates. The drug concentrations in mouse serum and tongues were measured following oral administration. IL-17-signalling-deficient Act1-/- mice were infected with fluconazole-susceptible or fluconazole-resistant C. albicans strains, and the amount of mucosal fungal burden was determined after fluconazole or VT-1161 treatment.
Results: Fourteen isolates (45%) were not fluconazole susceptible (MIC ≥4 mg/L). VT-1161 and VT-1129 showed significant in vitro activity against the majority of the 31 mucosal clinical isolates (MIC50 0.03 and 0.06 mg/L, respectively), including Candida glabrata (MIC50, 0.125 and 0.25 mg/L, respectively). After oral doses, VT-1161 and VT-1129 concentrations in mouse serum and tongues were well above their MIC50 values. VT-1161 was highly effective as treatment of both fluconazole-susceptible and -resistant oropharyngeal candidiasis in Act1-/- mice.
Conclusions: VT-1129 and VT-1161 exhibit significant in vitro activity against Candida strains, including fluconazole-resistant C. albicans and C. glabrata. VT-1161 administration in mice results in significant mucosal drug accumulation and eradicates infection caused by fluconazole-susceptible and -resistant Candida strains.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890729 | PMC |
| http://dx.doi.org/10.1093/jac/dkx352 | DOI Listing |
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Article Synopsis
- Candida albicans is a leading fungal pathogen causing chronic infections, especially in patients with certain immune deficiencies, prompting the need for new antifungal therapies due to rising azole resistance.
- The study tested the effectiveness of new drugs VT-1161 and VT-1129 against both azole-susceptible and azole-resistant strains of C. albicans using clinical isolates and a mouse model.
- Results showed that both drugs had strong in vitro activity against most strains, with VT-1161 proving particularly effective in clearing infections in a mouse model, even with resistant strains.
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