In vitro and in vivo efficacy of the triazole TAK-187 against Cryptococcus neoformans.
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.
Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
W A
WA
Schell
G M
GM
De Almeida
R K
RK
Dodge
K
K
Okonogi
J R
JR
Perfect
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D003453:Cryptococcosis / Q000188:drug therapy; D003455:Cryptococcus neoformans / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D014230:Triazoles / Q000494:pharmacology*; D005466:Fluorocarbons
D000935:Antifungal Agents; D014230:Triazoles; C105227:TAK 187; D005466:Fluorocarbons