ABSTRACT
In this study, we investigated the in vivo efficacy of anidulafungin during the early phase of disseminated candidiasis in a neutropenic murine model and compared the results with those obtained for fluconazole. Antifungal efficacy was evaluated by reduction of fungal burden in the tissues of infected animals at periodic intervals during the first day of treatment. The fungal burden in tissues of drug-treated mice was reduced compared with controls in a time-dependent manner. At 24h after drug treatment, a >2 log(10) reduction of fungal burden in the kidney was obtained in the anidulafungin- and caspofungin-treated mice compared with a ca. 1.2 log(10) reduction in fluconazole-treated mice (P<0.003). There was no significant difference in the splenic fungal burden at 24h. Thus, echinocandins have excellent antifungal activity in the early phase of disseminated Candida albicans infection and may contribute to an improved outcome in critically ill immunocompromised/neutropenic patients.
Subject(s)
Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Echinocandins/therapeutic use , Fluconazole/therapeutic use , Neutropenia/complications , Anidulafungin , Animals , Candida albicans/drug effects , Candida albicans/isolation & purification , Caspofungin , Colony Count, Microbial , Disease Models, Animal , Female , Humans , Immunocompromised Host , Kidney/microbiology , Lipopeptides , Mice , Mice, Inbred ICR , Spleen/microbiology , Treatment OutcomeABSTRACT
The fungal burdens (number of CFU per pair of lungs) in mice infected with Aspergillus fumigatus AB16.4 (for which the amphotericin B [AMB] MIC was elevated) and W73355 (drug-susceptible parent) were reduced by 21 and 81%, respectively, after 5 days of AMB treatment (2 mg/kg/day), indicating that AB16.4 also shows reduced susceptibility to AMB in a murine pulmonary aspergillosis model.
Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Aspergillus fumigatus/drug effects , Drug Resistance, Bacterial , Lung Diseases, Fungal/drug therapy , Lung/microbiology , Amphotericin B/pharmacology , Animals , Antifungal Agents/pharmacology , Aspergillosis/drug therapy , Aspergillosis/microbiology , Aspergillus fumigatus/isolation & purification , Colony Count, Microbial , Disease Models, Animal , Female , Humans , Laboratories , Lung Diseases, Fungal/microbiology , Mice , Mice, Inbred DBAABSTRACT
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.
