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The role of fluconazole in the early treatment and prophylaxis of experimental invasive aspergillosis.

Abstract
The efficacy of fluconazole against Aspergillus fumigatus was assessed in an immunosuppressed temporarily leukopenic rabbit model of invasive aspergillosis. Therapy with fluconazole at 60 or 120 mg/kg/day was begun 24 h after lethal challenge and compared to that with amphotericin B at 1.5 mg/kg/day. Fluconazole reduced mortality compared with that in untreated controls and at 120 mg/kg/day reduced the tissue burden of A. fumigatus 10- to 100-fold in liver, kidney, and lung. However, amphotericin B was more effective in sterilizing tissues. Both fluconazole and amphotericin B dramatically decreased or eliminated circulating aspergillus antigen. Prophylaxis with fluconazole, begun 48 h before sublethal challenge, sterilized liver and kidney tissues and significantly reduced the tissue burden in lung. Early treatment with fluconazole reduced mortality and reduced antigenemia but did not sterilize tissues. Fluconazole prophylaxis at these doses prevented dissemination of invasive aspergillosis. Fluconazole was shown to have activity in the early treatment and prophylaxis of experimental invasive aspergillosis.
AuthorsT F Patterson, D George, P Miniter, V T Andriole
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 164 Issue 3 Pg. 575-80 (Sep 1991) ISSN: 0022-1899 [Print] United States
PMID1869843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fluconazole
Topics
  • Animals
  • Aspergillosis (drug therapy, microbiology, mortality, prevention & control)
  • Aspergillus fumigatus (drug effects)
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Fluconazole (therapeutic use)
  • Immune Tolerance
  • Organ Specificity
  • Rabbits

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