title: Antifungal dynamics of LY 303366, an investigational echinocandin B analog, against Candida ssp.
abstract: 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 buffered morpholinepropanesulfonic acid (MOPS) was utilized as growth medium. Samples were obtained at predetermined time points over 24 hours and streaked for colony count determination. Against C. albicans (one strain) and C. glabrata isolates, LY 303366 exhibited fungicidal (> or = three log10 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 multiples of the MIC tested. With the exception of one C. glabrata strain, the 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 time of fungal exposure to the drug. Additionally, these data suggest that use of the current interpretive endpoint for MICs in RPMI may underestimate 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 303366 MICs.
authors.affiliation: Colleges of Pharmacy, University of Iowa, Iowa City, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Ernst
authors.forename: M E
authors.initials: ME
authors.lastname: Klepser
authors.forename: E J
authors.initials: EJ
authors.lastname: Wolfe
authors.forename: M A
authors.initials: MA
authors.lastname: Pfaller
mesh_terms: D000077612:Anidulafungin; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects; D054714:Echinocandins; D005656:Fungal Proteins; D006801:Humans; D008826:Microbial Sensitivity Tests; D010455:Peptides; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D000077612:Anidulafungin; C007572:echinocandin B