Activities of rifabutin, clarithromycin, and ethambutol against two virulent strains of Mycobacterium avium in a mouse model

Rifabutin, clarithromycin, and ethambutol, which were administered at concentrations similar to those used in clinical trials that are now under way, were tested for their capacities to inhibit the growth of two highly virulent isolates of Mycobacterium avium in inbred C57BL/6 mice and in vitro in a bone marrow-derived murine macrophage model. In the latter model rifabutin and clarithromycin had modest activities against strain 101 and somewhat better activities against strain 2-151. When they were tested in vivo, however, the best results, against strain 101 were seen when the three drugs were given in combination, whereas against strain 2-151 the combination therapy showed no significant improvement over that of clarithromycin given alone. It will be of interest to note to what degree the eventual outcomes of the current trials correlate with the predictions of these animal model systems.