In vitro pharmacodynamic properties of MK-0991 determined by time-kill methods.
MK-0991 has demonstrated activity against a variety of fungal pathogens. We evaluated the MIC endpoint for MK-0991 by reading the endpoint using three methods and comparing these results with minimum fungicidal concentrations and electron micrographs. The concentration that resulted in 80% inhibition of fungal growth compared with control, similar to the endpoint for the azole antifungal agents, provided the most consistent results. Additionally, we investigated the time-kill properties of this agent against two isolates each of Candida albicans, Candida glabrata and Candida tropicalis at concentrations ranging from 0.125 x MIC to 16 x MIC. Kill curves were performed using RPMI buffered with morpholine propanesulfonic acid as growth media. Samples were obtained at predetermined time points over 24 h and plated for colony counting. Fungicidal activity was observed with one isolate of C. albicans, two isolates of C. glabrata, and one isolate of C. tropicalis. MK-0991 displayed concentration-dependent activity, which was fungicidal or fungistatic depending on the isolate tested.
Ernst
E J
EJ
College of Pharmacy, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
Klepser
M E
ME
Ernst
M E
ME
Messer
S A
SA
Pfaller
M A
MA
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000648:ultrastructure; D000077336:Caspofungin; D054714:Echinocandins; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010455:Peptides; D010456:Peptides, Cyclic; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D000077336:Caspofungin