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 fungicidial 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 agonist two isolated 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. (C) 1999 Elsevier Science Inc.