BACKGROUND: Infections with Toxoplasma gondii poses a great hazard to immunocompromised patients and to pregnant women. Currently, the recommended therapy for toxoplasmosis is the synergistic combination of pyrimethamine and sulfadiazine (P/S). However, this therapeutic regimen may be toxic or only partially effective. Because pyrimethamine is potentially teratogenic, its use during the early months of pregnancy is not recommended. There is a critical need for newer and safer compounds for the treatment of toxoplasmosis. These considerations led us to evaluate other potential therapeutic agents--minocycline, clindamycin, roxithromycin, azithromycin, clarithromycin and miocamycin--as well as comparison of P/S and spiramycin efficacy against T. gondii. METHODS: The activity of antibiotics was tested in a murine model of acute toxoplasmosis. NMRI mice were infected intraperitoneally with 200 tachyzoites of the highly virulent RH strain of T. gondii, and treated, every 12 h or 24 h, for ten consecutive days. RESULTS: P/S (a dose of 4/250 mg/kg of body weight per day), minocycline (200 mg/kg) and azithromycin (200 mg/kg) were the most active compounds (100% of mice survival). Clindamycin, roxithromycin, spiramycin and clarithromycin were less effective. Miocamycin was not effective in this model. CONCLUSIONS: Our findings support the view that minocycline and azithromycin could be useful in many cases of toxoplasmosis. Clinical studies are needed to determinate the relative efficacy and safety of these antibiotics for the treatment of toxoplasmosis in humans.
BACKGROUND: Infections with Toxoplasma gondii poses a great hazard to immunocompromised patients and to pregnant women. Currently, the recommended therapy for toxoplasmosis is the synergistic combination of pyrimethamine and sulfadiazine (P/S). However, this therapeutic regimen may be toxic or only partially effective. Because pyrimethamine is potentially teratogenic, its use during the early months of pregnancy is not recommended. There is a critical need for newer and safer compounds for the treatment of toxoplasmosis. These considerations led us to evaluate other potential therapeutic agents--minocycline, clindamycin, roxithromycin, azithromycin, clarithromycin and miocamycin--as well as comparison of P/S and spiramycin efficacy against T. gondii. METHODS: The activity of antibiotics was tested in a murine model of acute toxoplasmosis. NMRI mice were infected intraperitoneally with 200 tachyzoites of the highly virulent RH strain of T. gondii, and treated, every 12 h or 24 h, for ten consecutive days. RESULTS:P/S (a dose of 4/250 mg/kg of body weight per day), minocycline (200 mg/kg) and azithromycin (200 mg/kg) were the most active compounds (100% of mice survival). Clindamycin, roxithromycin, spiramycin and clarithromycin were less effective. Miocamycin was not effective in this model. CONCLUSIONS: Our findings support the view that minocycline and azithromycin could be useful in many cases of toxoplasmosis. Clinical studies are needed to determinate the relative efficacy and safety of these antibiotics for the treatment of toxoplasmosis in humans.