title: CAN-296-P is effective against cutaneous candidiasis in guinea pigs.
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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Wayne State University, 427 Lande Building, 505E Canfield, Detroit, MI 48201, USA. benjosef@kci.wayne.edu
authors.forename: Avital M
authors.initials: AM
authors.lastname: Ben-Josef
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cutright
authors.forename: Elias K
authors.initials: EK
authors.lastname: Manavathu
authors.forename: Jack D
authors.initials: JD
authors.lastname: Sobel
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D002179:Candidiasis, Cutaneous / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D005944:Glucosamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000627:therapeutic use*; D006168:Guinea Pigs; D009089:Mucor / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; C111294:CAN 296; D005944:Glucosamine