An In Vitro Head-To-Head Comparison of Syn2836, Syn2869, Syn2903, Syn2921 Amphotericin B, Fluconazole, and Itraconazole against a Spectrum of 90 Clinically-Significant Fungi.



SynPhar Laboratories, Inc/Taiho Pharmaceutical Co. (SYN) have developed four investigational triazoles: Syn2836, Syn2869, Syn2903, and Syn2921, which were evaluated by head-to-head in vitro susceptibility testing against Amphotericin B (AMB), Fluconazole (FLU), and Itraconazole (ITRA) employing a panel of 90 clinical isolates received in the Fungus Testing Laboratory. Included were Candida albicans (CA) susceptible to FLU (10), CA resistant to FLU (10), C. glabrata (CG, 10), C. tropicalis (CT, 10), C. paratropicalis (CP, 10), C. krusei (CK, 5), C. lusitaniae 9CL 3), C. lipolytica (Cli, 1), C. guilliermondii (Cgu, 1), Cryptococcus neoformans (CN, 10), Aspergillus fumigatus (AF, 10), A. flavus (Afl, 5), A. terreus (AT, 3), and A. niger (AN, 2). Susceptibility testing for yeast fungi was accomplished using the method as outlined in NCCLS document M27-A. Macrobroth dilution testing of aspergilli was done according to this standard but modified by adjusting the inoculum to 1 X 104} as opposed to 0.5-2.5 X 103} as mandated for the yeast fungi. Other parameters include testing in RPMI-1640 with L-glutamine, without bicarbonate and buffered with MOPS for the Azoles antibiotic medium 3 (M3) for AMB. All tests were incubated at 35°C and read at both 24 and 48 hours. Test ranges for the SYN compounds and FLU were 0.125-64 micro g/ml, while AMB was 0.03-16 micro g/ml and ITRA was 0.015-8 micro g/ml. The minimum inhibitory concentration (MIC) was defined as the lowest concentration which resulted in an 80% reduction in turbidity as compared to a drug-free control tube for the azoles and no visible growth as compared to the drug-free tube for AMB. The geometric mean (GM) 48 hr MIC for SYN compounds against CA susceptible to FLU was 0.16-0.18 compared to a FLU mean of 0.28 and ITRA mean of 0.03. The GM 48 hr MIC for SYN compounds against CA resistant to FLU was 0.76-1.52 compared to FLU at 111.43 and ITRA at 0.75. Comparable results were obtained with the aspergilli with the GM 48 hr MIC for AF being 0.5-0.7 for the SYN compounds while FLU fell at 128.0 and ITRA at 0.268. These results indicate that the SYN compounds compared favorably with ITRA while being generally lower than FLU MICs. In vitro, the SYN compounds appear to have excellent activity against clinical isolates encompassing fungal species of major medical significance.

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38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th