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Treatment of experimental Toxoplasma gondii infection by Clarithromycin based combination therapies.


Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:139.

High efficacy of clarithromycin based therapies was demonstrated for treatment of experimental Toxoplasma gondii infection. Mice were infected intraperitoneally with 2 x 10(3) to 2 x 10(4) T. Gondii strain RH or TS4 tachyzoites. Mortality was recorded for 35 days and latency was evaluated by inoculation of brain homogenates from surviving mice into naive mice. The combination therapy of clarithromycin and pyrimethamine, or clarithromycin and minocycline caused a significantly (p less than 0.05) greater reduction in mortality than did either drug alone. A 100% cure rate of active and latent infection was achieved in mice treated with the clarithromycin based combination therapies, which was comparable to the standard sulfonamide based therapies. The in vitro MIC of clarithromycin against T. Gondii on a mouse macrophage monolayer was 150 mg/ml, while the MIC values for minocycline and pyrimethamine were 20 mg/kg and 1.25 mg/ml. The mechanisms of the therapeutic synergy are not clear since significant in vitro synergy between clarithromycin and either pyrimethamine or minocycline was not achieved and the serum concentrations were below the MIC values. Clarithromycin combined with minocycline or pyrimethamine could allow greater therapeutic flexibility and avoid the toxicity associated with pyrimethamine or sulfonamides. Clarithromycin based therapies could be especially useful in immunocompromised patients since clarithromycin monotherapy provides safe and effective treatment against several other opportunistic pathogens, including Mycobacterium avium.

Candida albicans/*DRUG EFFECTS Cell Division/DRUG EFFECTS Microbial Sensitivity Tests Saccharomyces cerevisiae/DRUG EFFECTS/GROWTH & DEVELOPMENT Tamoxifen/*PHARMACOLOGY ABSTRACT


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