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.
Schell
W A
WA
Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
De Almeida
G M
GM
Dodge
R K
RK
Okonogi
K
K
Perfect
J R
JR
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