Comparative activities of macrolide derivatives on murine listeriosis

The new macrolide derivatives such as clarithromycin, roxithromycin and azithromycin have only slightly stronger in vitro antibacterial activity on Listeria monocytogenes than the older derivatives such as erythromycin and spiramycin. In vivo, however, the new macrolides exert a much better therapeutic action on murine listeriosis. Among the new derivatives, clarithromycin is the most active. Azithromycin has one characteristic advantage: it is still active several days after cessation of therapy because of its long half-life. This strong therapeutic activity may be due to the known intracellular accumulation of macrolides in macrophages, which is essential for the eradication of intracellular bacteria such as L. monocytogenes. In spite of the strong intracellular accumulation the effector function of the defense system is not impaired, because the course of infection with a macrolide-resistant strain of L. monocytogenes in mice was not enhanced by macrolide treatment.