title: In vivo activity of the macrolide antibiotics azithromycin, roxithromycin and spiramycin against Toxoplasma gondii.
abstract: The macrolide antibiotics azithromycin, roxithromycin and spiramycin were examined in parallel for in vivo activity against Toxoplasma gondii. Azithromycin was considerably more active in protecting mice against death due to acute toxoplasmosis even when the other two antibiotics were used at twice its dose. The higher activity of azithromycin prompted a further examination of its activity against five different strains of Toxoplasma gondii, including two isolated from patients with AIDS. Although variable degrees of protection against death were noted, treatment with 200 mg/kg/day for ten days was sufficient to promote survival of 100% of mice infected with inocula as high as 1 x 10(5) tachyzoites of Toxoplasma gondii. 90% of mice inoculated with 1 x 10(5) tachyzoites of strain MO, isolated from an AIDS patient, and treated orally with 200 mg/kg/day for ten days survived the infection whereas only 40% of mice infected with the same inoculum of the SOU strain, also isolated from an AIDS patient, survived. Tissue concentrations of azithromycin were examined in treated infected and non-infected mice. In both groups of mice azithromycin attained high concentrations in liver, spleen and heart, which exceeded concurrent serum levels by 25- to 200-fold. The concentrations in the brain were almost tenfold higher than the concentrations in serum after treatment with 200 mg/kg/day for ten days. Moreover, the concentrations in brains of infected mice were approximately two-fold higher than in brains of non-infected mice.
authors.affiliation: Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, California 94301.
authors.forename: F G
authors.initials: FG
authors.lastname: Araujo
authors.forename: R M
authors.initials: RM
authors.lastname: Shepard
authors.forename: J S
authors.initials: JS
authors.lastname: Remington
mesh_terms: D000818:Animals; D017963:Azithromycin; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D051379:Mice; D015575:Roxithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D015572:Spiramycin / Q000494:pharmacology / Q000627:therapeutic use*; D014018:Tissue Distribution; D014122:Toxoplasma / Q000187:drug effects*; D014124:Toxoplasmosis, Animal / Q000188:drug therapy*
chemical_list: D015575:Roxithromycin; D004917:Erythromycin; D015572:Spiramycin; D017963:Azithromycin