MICs and MBCs of clarithromycin against Mycobacterium avium within human macrophages

The inhibitory and bactericidal activities of clarithromycin were determined quantitatively against the intracellular populations of five Mycobacterium avium strains growing in monocyte-derived human macrophages. The MICs were 1.0 microgram/ml, and the MBCs ranged from 16.0 to 64.0 micrograms/ml; these values were similar to the MICs and MBCs found in broth cultures at pH 7.4 and were substantially lower than those found in broth cultures at pHs 6.8 and 5.0. Since the intracellular environment has a neutral or even an acidic pH, relatively low MICs and MBCs found in macrophage cultures can be associated with the fact that the drug concentrations in macrophages are substantially higher than those in the medium in which these cells are cultivated. Pretreatment of the macrophages 2 days prior to infection decreased the MICs twofold in comparison with results of experiments in which the drug was added to already infected macrophages.