Toxoplasma gondii: fluconazole and itraconazole activity against toxoplasmosis in a murine model.
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.
Martins-Duarte
Erica S
ES
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, CCS Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.
Lemgruber
Leandro
L
de Souza
Wanderley
W
Vommaro
Rossiane C
RC
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D020128:Inhibitory Concentration 50; D017964:Itraconazole / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D013997:Time Factors; D014122:Toxoplasma / Q000187:drug effects; D014124:Toxoplasmosis, Animal / Q000188:drug therapy*
D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D017964:Itraconazole; D015725:Fluconazole