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Ketoconazole therapy of murine cryptococcal meningitis.

Abstract
Currently, even optimal therapy of cryptococcal meningitis is associated with appreciable mortality, drug toxicity, and prolonged hospitalization. Ketoconazole, a new oral imidazole, has therefore been evaluated in a murine model of cryptococcosis. Cryptococcal meningitis was induced in BALB/c mice by intracranial injection of Cryptococcus neoformans. The mice developed infection characterized by diffuse meningitis and extracerebral dissemination. Oral ketoconazole therapy prolonged survival of infected mice, but most mice ultimately succumbed to infection. Ketoconazole dramatically reduced the cryptococcal counts in the liver, but had minimal effect on counts in the brain. Paralleling these results were high concentrations of ketoconazole found in lung, spleen, and heart muscle and lower concentrations (2 to 5 micrograms/ml) found in the brain. The detection of biologically active drug in the brain, and the prolongation of survival afforded by ketoconazole, suggest a potential role for this agent in the theory of cryptococcal meningitis.
AuthorsP C Craven, J R Graybill, J H Jorgensen
JournalThe American review of respiratory disease (Am Rev Respir Dis) Vol. 125 Issue 6 Pg. 696-700 (Jun 1982) ISSN: 0003-0805 [Print] United States
PMID6283969 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antifungal Agents
  • Imidazoles
  • Piperazines
  • Ketoconazole
Topics
  • Animals
  • Antifungal Agents (therapeutic use)
  • Brain (microbiology)
  • Cryptococcosis (drug therapy, microbiology, mortality)
  • Cryptococcus neoformans (isolation & purification)
  • Female
  • Imidazoles (therapeutic use)
  • Ketoconazole
  • Liver (microbiology)
  • Male
  • Meningitis (drug therapy, microbiology, mortality)
  • Mice
  • Mice, Inbred BALB C
  • Piperazines (therapeutic use)

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