Disseminated aspergillosis due to Aspergillus flavus in an experimental model: efficacy of azole therapy.

The aim of this investigation was to create a reproducible experimental model of disseminated Aspergillus flavus aspergillosis, and to compare the relative therapeutic efficacies of itraconazole and fluconazole in this model. Temporarily immunosuppressed male Wistar rats received intravenous challenge by A. flavus conidia. Treatment was initiated 24 h later with oral itraconazole (1 mg kg-1 BW day-1), oral fluconazole (1 mg kg-1 BW day-1) or excipient only (infected-untreated rats); this was continued for 10 days. At this time, although 100% mortality had occurred among all infected-untreated rats, no mortality was noted among the control-uninfected, infected-itraconazole-treated or infected-fluconazole-treated rats. After killing, essential organs were processed for microbiological and histopathological studies. Aspergillus flavus was recovered in high colony counts from the organs of infected-untreated rats (lungs > liver > brain > kidneys), but in significantly lower colony counts, or not at all, from the organs of itraconazole-treated and fluconazole-treated rats. Histopathological alterations were pronounced in tissues of infected-untreated rats, but less so in treated rats. These data suggest that administration of itraconazole or fluconazole sufficiently early may prevent, or retard, progression of lesions in disseminated aspergillosis.