CAN-296-P is effective against cutaneous candidiasis in guinea pigs

• Published in: International journal of antimicrobial agents 2003-08, Vol.22 (2), p.168-171
• Main Authors: Ben-Josef, Avital M., Cutright, Jessica L., Manavathu, Elias K., Sobel, Jack D.
• Format: Article
• Language: English
• Subjects: Administration, Topical; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agent; Antifungal agents; Antifungal Agents - administration & dosage; Antifungal Agents - isolation & purification; Antifungal Agents - therapeutic use; Biological and medical sciences; Candida albicans; Candidiasis, Cutaneous - drug therapy; Complex carbohydrate; Disease Models, Animal; Female; Glucosamine - administration & dosage; Glucosamine - analogs & derivatives; Glucosamine - isolation & purification; Glucosamine - therapeutic use; Guinea Pigs; In vivo fungal infection; Medical sciences; Mucor - chemistry; Pharmacology. Drug treatments
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/S0924-8579(03)00111-0

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 ≥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.