SPK-843, a New Polyene Antibiotic with Potent In Vitro Activity and a Strong Fungicidal Effect.

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Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy


Background: Not only low MIC levels but also a more rapid fungicidal effect than existing antifungals would be required for the successful treatment for deep-seated mycosis. SPK-843, a new parenteral antifungal polyene, was examined for its in vitro antifungal activity and fungicidal potency. Methods/Results: The antifungal activity of SPK-843 against 107 clinical isolates of Candida spp., 12 of Cryptococcus neoformans, and 31 of Aspergillus spp. was compared to those of amphotericin B (AMPH), fluconazole (FLCZ) and other antifungals using a broth microdilution method specified by NCCLS. The geometric mean MIC values in µg/mL of SPK-843 versus AMPH were 0.268 vs. 0.445 for Candida albicans, 0.293 vs. 0.25 for C. glabrata, 0.233 vs. 0.467 for C. krusei, 0.149 vs. ?0.132 for Cryptococcus neoformans, 0.287 vs. 0.66 for Aspergillus flavus, 0.441 vs. 0.266 for A. fumigatus, and ?0.051 vs. 0.205 for A. niger, respectively. The frequency (%) of relatively insensitive strains (MIC: over 0.5 µg/mL) to SPK-843, AMPH and FLCZ was 4, 7 and 41 for Candida spp., 0, 0 and 50 for C. neoformans, and 6, 13 and 100 for Aspergillus spp., respectively. The fungicidal action of SPK-843 against C. albicans and C. neoformans was compared to those of AMPH and FLCZ in a time-kill study using MOPS-buffered RPMI1640. SPK-843 at 0.125-2 µg/mL decreased viable cells of C. albicans and C. neoformans more rapidly (below the assay limit within 30-60 minutes) than in the same concentrations of AMPH. Conclusion: The well-balanced MICs with no resistant strain and the rapid fungicidal action of SPK-843 revealed a more distinctive antifungal potency from any other existing antifungals, proving its clinical usefulness against deep-seated mycosis.

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Conference Year: 2000

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