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

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

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.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Cryptococcosis / microbiology
  • Cryptococcus neoformans / drug effects*
  • Cryptococcus neoformans / isolation & purification
  • Drug Resistance, Fungal*
  • Fluconazole / pharmacology*
  • Humans
  • Microbial Sensitivity Tests
  • Pyridines / pharmacology*
  • Tetrazoles / pharmacology*

Substances

  • Antifungal Agents
  • Pyridines
  • Tetrazoles
  • VT-1129
  • Fluconazole