Comparison of d0870 and fluconazole in the treatment of murine cryptococcal meningitis

A. L. Correa, G. Velez, M. Albert, M. Luther, M. G. Rinaldi, J. R. Graybill

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Cryptococcal meningitis is a common infection in patients with AIDS. Using a murine cryptococcosis model, we compared treatment with a new triazole, D0870, and fluconazole. Groups of ICR (Institute for Cancer Research) mice were infected intracerebrally with eight different isolates of Cryptococcus neoformans variety neoformans with different in vitro susceptibilities to fluconazole. For survival studies mice were challenged with two to four times LD50 or six to nine times LD50. Treatment was given for 10 days. Mice were observed through to day 30. To assess the effect of treatment on fungal tissue burden, mice received a three to five times LD50 inoculum and treatment for 10 days. They were sacrificed on day 12 and serial dilutions of brain homogenates were cultured. Fluconazole prolonged survival primarily in isolates which were susceptible in vitro. D0870 prolonged survival in all isolates except one, which was also resistant in vitro to D0870 and fluconazole. Both drugs reduced colony counts of all isolates. D0870 warrants further development for use in cryptococcosis, and appears effective for isolates relatively resistant to fluconazole. There is a relative correlation of in vivo and in vitro susceptibility to D0870 as well as fluconazole.

Original languageEnglish (US)
Pages (from-to)367-374
Number of pages8
JournalMedical mycology
Volume33
Issue number6
DOIs
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Infectious Diseases

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