Toxoplasma gondii: fluconazole and itraconazole activity against toxoplasmosis in a murine model.

Abstract

Toxoplasma gondii is an important opportunistic pathogen affecting immunocompromised patients with AIDS. Toxoplasmic encephalitis is responsible for high morbidity and mortality. In this study, we investigated the activity of the antifungals fluconazole (FLZ) and itraconazole (ITZ) against T. gondii in mice infected with the Me49 strain. As previously reported for ITZ, FLZ also demonstrated a selective effect against T. gondii in vitro; the IC(50) values obtained for FLZ were 8.9 microM and 3.1 microM after 24h and 48 h of treatment, respectively. A 10-day treatment of mice with orally or intraperitoneally administered 20mg/kg/day FLZ showed a significant survival difference compared to untreated mice. The administration of 20mg/kg/day ITZ significantly reduced the brain cyst burden compared to untreated mice but did not exert significant protection against death. The results obtained in this work are rather promising as ITZ and FLZ are safe and low-cost drugs available on the market.