Abstract
Because combination therapy is required to treat human toxoplasmosis, we examined combinations of the ketolides HMR 3004 and HMR 3647 with atovaquone, clindamycin or sulphadiazine in a murine model of toxoplasmosis. An oral dose of 50 mg/kg/day of HMR 3004 protected 30% of mice lethally infected with Toxoplasma gondii. The same dose protected 100% of infected mice when administered in combination with non-protective doses of atovaquone, clindamycin or sulphadiazine. Similar results were noted with 25 mg/kg/day of HMR 3647. These results demonstrate that these drug combinations are highly effective for treating toxoplasmosis in mice.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Bacterial Agents / administration & dosage
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Anti-Bacterial Agents / therapeutic use*
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Antiprotozoal Agents / administration & dosage
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Antiprotozoal Agents / therapeutic use*
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Atovaquone
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Clindamycin / administration & dosage
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Clindamycin / therapeutic use*
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Drug Therapy, Combination
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Female
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Ketolides*
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Macrolides*
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Mice
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Naphthoquinones / administration & dosage
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Naphthoquinones / therapeutic use
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Sulfadiazine / administration & dosage
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Sulfadiazine / therapeutic use
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Toxoplasma
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Toxoplasmosis, Animal / drug therapy*
Substances
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Anti-Bacterial Agents
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Antiprotozoal Agents
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Ketolides
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Macrolides
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Naphthoquinones
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RU 64004
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Sulfadiazine
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Clindamycin
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telithromycin
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Atovaquone