ABSTRACT
CAN-296 is a naturally occurring, heat-stable complex carbohydrate isolated from the cell wall of Mucor rouxii. Previously, CAN-296 demonstrated impressive in vitro fungicidal activity against a wide spectrum of pathogenic yeast, including azole-resistant isolates. The effect of CAN-296 on Candida albicans is rapid, concentration-dependent, and lethal. CAN-296-P is a chitosan-pyrithione derivative of CAN-296 containing 4% solution of chitosan with 25% substitution of pyrithione. Like CAN-296, it has in vitro fungicidal activity with a minimum inhibitory concentration (MIC) of 0.156 mg/l for C. albicans. The therapeutic effect of topical CAN-296-P on cutaneous candidiasis caused by C. albicans in guinea pigs was investigated. Three different C. albicans isolates, including one fluconazole-resistant strain (R 637601-9), were tested. After immunosuppression with cyclophosphamide, infection under occlusive dressing was achieved and treated within 48 h after the initial infection. Once-a-day topical application of 0.125, 0.25, 0.5, 1, 2, and 4% CAN-296-P solution was administrated for a period of 1, 3, 5, and 7 days. CAN-296-P at a concentration > or =0.25% was found to be as effective in clearing the infection as was 2% miconazole. Effectiveness in eradicating candidiasis with CAN-296-P was concentration-dependent and free of local adverse effects. Can-296-P is a novel, highly active topical fungicidal agent, with broad potential for clinical use.
