ERNST EJ, ROLING EE, KEELE DJ, KLEPSER ME; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. A-2204.

University of Iowa College of Pharmacy, Iowa City, IA

BACKGROUND: FK-463 is an investigational, echinocandin antifungal agent, isolated from the culture broth of Coleophoma empedri. We sought to characterize the post antifungal effects (PAFE) of FK-463 against Candida species. METHODS: Ten isolates, four C. albicans and two of each C. tropicalis, C. krusei, and C. glabrata were selected for testing. MICs were determined prior to testing by adapting approved NCCLS methods for FK-463. PAFEs were determined using a standard inoculum (1-5x10[5 ]CFU/ml) of yeast suspended in RPMI with MOPS culture medium alone or with FK-463 at concentrations of 0.25, 1, or 4xMIC. Yeast were incubated at 35 degreesC for 0.5 hours, followed by three cycles of centrifugation and resuspension in warm media for drug removal. Samples were removed at predetermined time points, diluted and plated on potato dextrose agar for colony counting up to 22 hours following the final wash. The colony counts were graphed versus time and the resulting curve fit using the 3 parameter Hill equation. The PAFE was calculated as the difference in time for control and test isolates to grow 1 log[10] above that observed following drug removal. RESULTS: MICs ranged from 0.0039 microg/ml to 0.25 microg/ml for all test isolates. A PAFE was observed for each isolate tested. The PAFE was influenced by concentration, with the highest concentration resulting in the longest observed PAFE in each case. At 0.25xMIC, observed PAFEs ranged from -0.4 to 0.5, -0.02 to 2, 2.4 to 4, and 0.09 to 0.19 hours for C. albicans, C. tropicalis, C. krusei, and C. glabrata, respectively. At concentrations equal to the MIC PAFEs ranged from -0.3 to 11 hours. The highest concentration tested, 4xMIC, resulted in PAFE of more than 9.8 hours in 5/10 isolates tested (range 0.9 to >19.5 hours). CONCLUSIONS: FK-463 produced a measurable PAFE against all Candida species tested, which was enhanced by increasing the concentration tested.

Publication Types:

• Meeting Abstracts

Keywords:

• Antifungal Agents
• Candida
• Lipoproteins
• Miconazole
• Microbial Sensitivity Tests
• Peptides, Cyclic
• micafungin

Other ID:

• GWAIDS0028954

UI: 102268586

From Meeting Abstracts