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. 2017 Jun 1;55(4):453-456.
doi: 10.1093/mmy/myw089.

Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs

Kirsten Nielsen  1 , Priya Vedula  1 , Kyle D Smith  1 , David B Meya  2 , Edward P Garvey  3 , William J Hoekstra  3 , Robert J Schotzinger  3 , David R Boulware  4
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Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs

Kirsten Nielsen et al. Med Mycol. .

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.

Keywords: CYP51; Cryptococcus; VT-1129; antifungal; azole.

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