Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs.
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.
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
Kirsten
K
Nielsen
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
Priya
P
Vedula
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
Kyle D
KD
Smith
Infectious Diseases Institute, Makerere University, Kampala, Uganda.
David B
DB
Meya
Viamet Pharmaceuticals, Inc., Durham, NC, USA.
Edward P
EP
Garvey
Viamet Pharmaceuticals, Inc., Durham, NC, USA.
William J
WJ
Hoekstra
Viamet Pharmaceuticals, Inc., Durham, NC, USA.
Robert J
RJ
Schotzinger
Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
David R
DR
Boulware
D000935:Antifungal Agents / Q000494:pharmacology*; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011725:Pyridines / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*
D000935:Antifungal Agents; D011725:Pyridines; D013777:Tetrazoles; C000612857:VT-1129; D015725:Fluconazole
CYP51; Cryptococcus; VT-1129; antifungal; azole