In vitro pharmacodynamic properties of MK-0991 determined by time-kill methods

Diagn Microbiol Infect Dis. 1999 Feb;33(2):75-80. doi: 10.1016/s0732-8893(98)00130-8.

Abstract

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.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / pharmacology*
  • Candida / drug effects*
  • Candida / ultrastructure
  • Caspofungin
  • Echinocandins
  • Lipopeptides
  • Microbial Sensitivity Tests
  • Peptides*
  • Peptides, Cyclic*
  • Time Factors

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Peptides
  • Peptides, Cyclic
  • Caspofungin