title: Treatment of experimental Toxoplasma gondii infection by clarithromycin-based combination therapy with minocycline or pyrimethamine.
abstract: The efficacy of clarithromycin combined with either pyrimethamine or minocycline for treatment of experimental Toxoplasma gondii infection was investigated. 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 postinfection. Latency was evaluated by inoculation of brain homogenates from surviving mice into naive untreated mice. The combination of clarithromycin and pyrimethamine therapy caused a significantly greater reduction in mortality than did either drug alone. Similar synergy was observed between clarithromycin and minocycline. A 100% cure rate of active and latent infection was achieved in mice treated with the clarithromycin based combinations. Clarithromycin in combination with either pyrimethamine or minocycline produced efficacy comparable to combined therapy of pyrimethamine with sulfamethoxazole. The in vitro potency of clarithromycin, pyrimethamine, or minocycline against T. gondii on a mouse macrophage monolayer was not predictive of the in vivo efficacy in mice. Clarithromycin combined with minocycline or pyrimethamine could allow greater flexability for treatment of patients predisposed to the toxicity associated with standard pyrimethamine-sulfonamide or pyrimethamine-nonsulfonamide therapy. This therapy could be especially useful since clarithromycin-based therapy provides safe and effective treatment against Mycobacterium avium complex infections associated with AIDS patients.
authors.affiliation: Department of Anti-infective Microbiology, Abbott Laboratories, Abbott Park, Illinois 60064-3500.
authors.forename: J
authors.initials: J
authors.lastname: Alder
authors.forename: T
authors.initials: T
authors.lastname: Hutch
authors.forename: J A
authors.initials: JA
authors.lastname: Meulbroek
authors.forename: J C
authors.initials: JC
authors.lastname: Clement
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000818:Animals; D017291:Clarithromycin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D051379:Mice; D008911:Minocycline / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011739:Pyrimethamine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013420:Sulfamethoxazole / Q000627:therapeutic use; D014122:Toxoplasma / Q000187:drug effects; D014124:Toxoplasmosis, Animal / Q000188:drug therapy*
chemical_list: D008911:Minocycline; D017291:Clarithromycin; D013420:Sulfamethoxazole; D011739:Pyrimethamine