TREATMENT OF EXPERIMENTAL TOXOPLASMA-GONDII INFECTION BY CLARITHROMYCIN-BASED COMBINATION THERAPY WITH MINOCYCLINE OR PYRIMETHAMINE

The efficacy of clarithromycin combined with either pyrimethamine or m inocycline for treatment of experimental Toxoplasma gondii infection w as investigated. Mice were infected intraperitoneally with 2 x 10(3) t o 2 x 10(4) T. gondii strain RH or TS4 tachyzoites. Mortality was reco rded for 35 days postinfection. Latency was evaluated by inoculation o f brain homogenates from surviving mice into naive untreated mice. The combination of clarithromycin and pyrimethamine therapy caused a sign ificantly greater reduction in mortality than did either drug alone. S imilar synergy was observed between clarithromycin and minocycline. A 100% cure rate of active and latent infection was achieved in mice tre ated with the clarithromycin based combinations. Clarithromycin in com bination with either pyrimethamine or minocycline produced efficacy co mparable to combined therapy of pyrimethamine with sulfamethoxazole. T he in vitro potency of clarithromycin, pyrimethamine, or minocycline a gainst T. gondii on a mouse macrophage monolayer was not predictive of the in vivo efficacy in mice. Clarithromycin combined with minocyclin e or pyrimethamine could allow greater flexability for treatment of pa tients predisposed to the toxicity associated with standard pyrimetham ine-sulfonamide or pyrimethamine-nonsulfonamide therapy. This therapy could be especially useful since clarithromycin-based therapy provides safe and effective treatment against Mycobacterium avium complex infe ctions associated with AIDS patients.