Effect of rifabutin on the phagocytosis and intracellular growth of Mycobacterium intracellulare in mouse resident and activated peritoneal and alveolar macrophages.

In order to understand the discrepant results between in vitro and in vivo activity of rifabutin (LM 427) against Mycobacterium intracellulare, we studied its effects upon the phagocytosis of M. intracellulare by resident and activated mouse peritoneal and alveolar macrophages and upon growth of M. intracellulare inside these cells. Rifabutin (ansamycin, LM 427) had no effect on the viability of resident or activated peritoneal or alveolar macrophages or on the phagocytosis of M. intracellulare by resident peritoneal macrophages. In activated peritoneal and alveolar macrophages, it had a dose-related effect on the phagocytic index and intracellular growth of M. intracellulare. Macrophages from mice pretreated with 10 or 20 mg/kg of rifabutin either orally or intraperitoneally for 4 to 10 days showed inhibition of intracellular growth of M. intracellulare in a dose-related manner. The route of administration or further addition of the drug did not enhance the inhibitory activity of these macrophages. These results indicate that rifabutin has the potential of killing M. intracellulare persisters inside macrophages.