TREATMENT OF SYSTEMIC CANDIDIASIS IN NEUTROPENIC DOGS WITH KETOCONAZOLE

Google Scholar
  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (8) , 791-795
Abstract
The present study evaluated the activity of ketoconazole in neutropenic dogs with systemic candidiasis. Five dog pairs were made neutropenic by intravenous cyclophosphamide (50 mg/kg) and challenged with either 106 or 107 colony-forming units (CFU) of Candida albicans. Half of the dogs received ketoconazole (10 mg/kg) daily beginning 24 h after challenge. All were killed at 96 h and liver, spleen, and kidney were cultured. Of four dogs given 106 CFU, to untreated dogs had 9 .times. 103 to 1 .times. 105 CFU/g wet tissue, compared to 0 CFU in ketoconazole-treated dogs. With inoculum increased to 107 CFU, three untreated dogs had 2 .times. 104 to 3 .times. 105 CFU/g wet tissue, while three ketoconazole dogs had 0-5 .times. 105 CFU/g wet tissue. The effect of ketoconazole on autologous marrow reconstitution in dogs with systemic candidiasis was examined by infusing autologous cryopreserved marrow into four dogs one day after lethal whole body irradiation (800 rad). Once neutropenic, they were challenged with 107 CFU of C. albicans. Two dogs received no ketoconazole and died of disseminated candidiasis, without marrow reconstitution. Two dogs received ketoconazole for 25 days. Prompt marrow recovery occurred and they remained healthy. There was no evidence of infection at death. These studies quantitatively demonstrate the in vivo effectiveness of ketoconazole in reducing tissue infection with C. albicans in neutropenic dogs. They provide in vivo evidence that ketoconazole can prevent or cure systemic candidiasis in the bone marrow transplant setting without significant inhibition of marrow recovery.