ANTIFUNGAL DYNAMICS OF LY-303366, AN INVESTIGATIONAL ECHINOCANDIN-B ANALOG, AGAINST CANDIDA SSP

Two isolates each of Candida albicans, Candida tropicalis, and Candida glabrata were selected for time-kill curve testing against LY 303366 at concentrations ranging from 0.125 x MIC to 16 x MIC. RPMI 1640 buff ered with morpholinepropanesuulfonic acid (MOPS) was utilized as growt h medium. Samples were obtained at predetermined time points over 24 h ours and streaked for colony count determination. Against C. albicans (one strain) and C. glabrata isolates, LY 303366 exhibited fungicidal (greater than or equal to three log(10) reduction in CFU) activity. In contrast, fungistatic activity was observed with LY 303366 against C. albicans (one strain) and C. tropicalis isolates at all of the multip les of the MIC tested. With the exception of one C. glabrata strain, t he rate and extent of activity against test isolates was not enhanced with concentrations exceeding the MIC. Our data indicate that maximal antifungal activity with LY 303366 may be achieved by optimizing the t ime of fungal exposure to the drug. Additionally, these data suggest t hat use of the current interpretive endpoint for MICs in RPMI may unde restimate the antifungal activity of LY 303366. Thus, the MIC endpoint may need to be re-evaluated, or perhaps an alternative media, such as antibiotic medium #3, should be utilized for determination of LY 3033 66 MICs. (C) 1997 Elsevier Science Inc.