In vitro and in vivo efficacy of the triazole TAK-187 against Cryptococcus neoformans.

Abstract

Multiple isolates of Cryptococcus neoformans, including those with fluconazole resistance, were tested to assess the in vitro activity of the new triazole TAK-187. MICs of TAK-187 were at least eightfold lower than those of fluconazole, and fungicidal concentrations for most isolates were 4 microg/ml or less. TAK-187 also was evaluated as intermittent therapy using two dosages in a rabbit model of experimental cryptococcal meningitis. Compared to daily treatment with fluconazole, as little as two doses of TAK-187 given 7 days apart were found to be effective. Plasma and cerebrospinal fluid TAK-187 concentrations were many times higher than MICs and fungicidal concentrations. Based upon its therapeutic efficacy and long half-life in the rabbit model, TAK-187 should be investigated for intermittent dosing in treatment or suppression of cryptococcal infections in humans.

• Authors: W A Schell, G M De Almeida, R K Dodge, K Okonogi, J R Perfect
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 42 Issue 10 Pg. 2630-2 (Oct 1998) ISSN: 0066-4804 [Print] United States
• PMID: 9756767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Triazoles
• TAK 187

Topics

• Animals
• Antifungal Agents (pharmacology)
• Cryptococcosis (drug therapy)
• Cryptococcus neoformans (drug effects)
• Microbial Sensitivity Tests
• Rabbits
• Triazoles (pharmacology)