Activity of azithromycin against Leishmania major in vitro and in vivo.

Azithromycin, an azalide antibiotic of the macrolide family, concentrates in the tissues and especially in macrophages. Because Leishmania parasites reside in these cells, we tested this antibiotic for a possible antileishmanial activity in vitro and in vivo. Azithromycin decreased the Leishmania major promastigote count in cell-free cultures at log phase approximately 50-fold. In macrophage cultures infected with L. major amastigotes, azithromycin caused a significant decrease in parasite levels with an ED50 of 12 microg/ml. The activity in vivo was evaluated after infection of the footpads of susceptible BALB/cByJ mice and resistant C57BL/6J mice with L. major. Treatment of BALB/cByJ mice with azithromycin, 100 to 200 mg/kg/d, resulted in a significant decrease in lesion size and in the number of parasites per lesion, whereas no effect was seen in the treated C57BL/6J mice. Azithromycin has activity against L. major in vitro and in vivo. Given the severity of the disease and the limitations of the available therapeutic agents, azithromycin may have a significant role in the treatment of this group of diseases.