The efficacy of clarithromycin in a murine model of acute toxoplasmosis was studied. Clarithromycin was administered alone and concurrently with minocycline, and eficacy was assessed by survival rates and sequential determination of parasite burden in blood, brains, and lungs. ILmited protection resulted from administration of each drug alone, whereas a remarkable synergistic effect followed concurrent administration.Survival of mice treated with 200 mg of clarithromycin plus 20 mg of minocycline per kg of body weight dalfy was 95%; that of mice treated with 50 mg of clarithromycin plus 50 mg of minocycline per kg daily was 93%.The parasite burden in the blood and organ tissues of these mice was markedly reduced compared with that in mice treated with a single agent. In mice treated with 200 mg of carithromycin plus 50 mg of minocyline per kg per day, survival was 100%o during the 30-day experliment; no parasites were found in blood and tissues.The combination of pyrimethamine and sulfadiazine is the standard therapy for toxoplasmic encephalitis. However, the incidence of side effects is high; skin reaction due to the sulfonamide and hematologic toxicity due to pyrimethamine have been reported with high frequency (8). Alternative regimens involving the replacement of one of the two components by another drug are currently being investigated. The combination of pyrimethamine plus clindamycin and the combination of pyrimethamine plus clarithromycin proved efficient for treatment of patients with toxoplasmic encephalitis (5, 7); other drug combinations using a macrolide have also been effective in an experimental model of acute toxoplasmosis (6). We designed a study to identify a combination of drugs that might make the use of folate inhibitors unnecessary. Since clarithromycin and minocycline are individually active against Toxoplasma gondii (3, The treatment regimens associated with at least 50% survival by day 30 were then reevaluated by using larger groups of mice. Both survival rate and the kinetics of blood and tissue infection were evaluated. In these larger-sample experiments, mice were randomly allocated to separate groups: 30 mice served as controls (no treatment), and each treatment group consisted of 40 mice. The regimens con- Mice were studied for 30 days after infection. Monitoring of infection involved the estimation of survival rates by using the Kaplan Meier product limit method and sequential examination of parasite burden in blood, brains, and lungs on days 4, 7, 10, 14, 22, and 30 after infection; on day 30, liver and spleen tissues were also examined. At each time point, five mice from each group were sacrificed and blood and organ homogenates were cultured as described previously (12). Briefly, serial fourfold dilutions of each blood or organ suspension were prepared in the culture medium, and then 40 ,ul of each dilution was inoculated into duplicate wells of tissue culture plates.
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