Therapy of systemic histoplasmosis in immunosuppressed mice with the triazole D0870.
Because histoplasmosis is a life-threatening disease in AIDS and other compromised patients, we examined the efficacy of D0870 (Zeneca) in immunosuppressed mice against systemic histoplasmosis. Oral therapy with fluconazole given once daily (QD) was ineffective in prolonging survival, whereas itraconazole given once or twice daily (BID), fluconazole given BID or D0870 given QD or given every other day (QOD) were efficacious (P < 0.001). Burdens of Histoplasma capsulatum in the liver and spleen of survivors showed that D0870 given QD or QOD and itraconazole given BID caused dose-responsive reduction of infectious burden. Infection was cleared more readily from the liver than from the spleen. Overall, D0870 was > or = 20-fold more efficacious than fluconazole or itraconazole and itraconazole was > ten-fold better than fluconazole for the treatment of systemic histoplasmosis in the immunosuppressed model.
Clemons
K V
KV
Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128, USA.
Martinez
M
M
Homola
M E
ME
Stevens
D A
DA
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D003348:Cortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use; D006660:Histoplasmosis / Q000188:drug therapy* / Q000276:immunology; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017964:Itraconazole / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D014230:Triazoles / Q000627:therapeutic use*
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D014230:Triazoles; C058219:ICI 195739; D017964:Itraconazole; D015725:Fluconazole; D003348:Cortisone