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

Abstract

Summary 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.

rmtA-Dependent Transcriptome and Its Role in Secondary Metabolism, Environmental Stress, and Virulence inAspergillus flavus

“…In addition to its devastating effect on crops of economic importance, A. flavus is known to cause a deadly lung infection known as invasive aspergillosis. Although A. flavus is the second leading cause of IA after Aspergillus fumigatus , A. flavus is 100-fold more virulent than that of A. fumigatus (Ford and Friedman 1967; Mosquera et al 2001; Kamai et al 2002, Kaliamurthy et al 2003 Hedayati et al 2007).…”