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In vivo activity of the macrolide antibiotics azithromycin, roxithromycin and spiramycin against Toxoplasma gondii
F G Araujo1, R M Shepard, J S Remington
1Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, California 94301.
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.
Insights
Azithromycin shows superior in vivo activity against Toxoplasma gondii compared to other macrolides. This antibiotic effectively protected mice against toxoplasmosis, even in strains from AIDS patients.
Area of Science:
- Infectious Diseases
- Pharmacology
- Immunology
Background:
- Toxoplasma gondii is an opportunistic parasite causing toxoplasmosis.
- Macrolide antibiotics are used to treat various infections.
- The efficacy of macrolides against T. gondii requires further investigation.
Purpose of the Study:
- To compare the in vivo activity of azithromycin, roxithromycin, and spiramycin against Toxoplasma gondii.
- To evaluate the effectiveness of azithromycin against different strains of T. gondii, including those from immunocompromised patients.
- To determine azithromycin tissue distribution in infected and non-infected mice.
Main Methods:
- In vivo efficacy study in mice infected with T. gondii.
- Comparative treatment with azithromycin, roxithromycin, and spiramycin.
- Assessment of survival rates and tissue drug concentrations.
Main Results:
- Azithromycin demonstrated significantly higher activity than roxithromycin and spiramycin in protecting mice against acute toxoplasmosis.
- Azithromycin treatment (200 mg/kg/day for 10 days) resulted in 100% survival in mice infected with high inocula of T. gondii.
- High concentrations of azithromycin were found in mouse tissues, particularly the brain, exceeding serum levels.
Conclusions:
- Azithromycin is a highly effective macrolide antibiotic for treating toxoplasmosis in vivo.
- Azithromycin's favorable tissue distribution, especially in the brain, contributes to its efficacy.
- Further research into azithromycin for toxoplasmosis treatment is warranted.