[New pathogens and mode of action of azithromycin: Toxoplasma gondii]

Azithromycin can inhibit the growth of Toxoplasma gondii tachyzoïtes in vitro, but the effect is only observed with prolonged incubation with the drug, reflecting the delayed mode of action of this macrolide on the parasite. Azithromycin is probably acting by inhibition of protein synthesis but the site of action and fixation in the parasite has not been demonstrated. Azithromycin is also effective against intracystic bradyzoïtes in vitro, but long term administration of azithromycin to chronically infected mice failed to reduce the mean number of brain cysts. In models of acute toxoplasmosis, azithromycin was found to have a limited effect on brain infection, whereas parasites were cleared from blood and lungs of infected mice, resulting in a significant protection of treated mice comparatively to untreated controls. When azithromycin is combined with pyrimethamine or sulfadiazine, an additive effect is observed in vitro, and a remarkable synergistic effect is observed in vivo in the treatment of acute toxoplasmosis. Together, these results are in favor of the use of azithromycin in combined therapies for the treatment and/or prophylaxis of toxoplasmosis.