Antibacterial effect of telithromycin (HMR 3647) and comparative antibiotics against intracellular Legionella pneumophila

The activity of the ketolide telithromycin (HMR 3647) against intracellular Legionella pneumophila strain L-1033 was compared with the activities of erythromycin and levofloxacin. To assay intracellular antibacterial activity, human monocytes were allowed to adhere to wells in 24-well tissue culture plates and were then exposed to L. pneumophila cells for 1 h to allow phagocytosis to occur. Antibiotics were added to the wells after removal of unphagocytosed bacteria. Quantitative bacterial cell counts were made from lysed monocytes at 0, 24, 48, 72 and 96 h. The antibacterial effects of antibiotics against intracellular L. pneumophila L-1033 were concentration and time dependent; at 10 x MIC the activity of telithromycin was greater than that of erythromycin and was less than that of levofloxacin (P < 0.01); telithromycin-rifampicin combinations showed no synergy or interference; and removal of telithromycin from assays at 24 h did not affect its intracellular antibacterial activity. In conclusion, the ketolide telithromycin has excellent activity against intracellular L. pneumophila strain L-1033 and should be evaluated for therapy of legionnaires' disease.