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

Alejandro KrolewieckiDepartment of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

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Shalom LeonDepartment of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

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Phillip ScottDepartment of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

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David AbrahamDepartment of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

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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.

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