In vitro activities of the ketolides telithromycin (HMR 3647) and HMR 3004compared to those of clarithromycin against slowly growing mycobacteria atpHs 6.8 and 7.4

The in vitro activities of HMR 3647 (telithromycin) and HMR 3004, two novel semisynthetic ketolides, were investigated and compared with that of the r eference macrolide drug, clarithromycin, against 34 strains of slowly growi ng mycobacteria at pHs 6.8 and 7.4, as determined radiometrically, The MICs at pH 7.4 were about 1 to 2 dilutions lower than those observed at pH 6.8. in terms of the highest to the lowest activity; the three antibiotics coul d be classified as follows: clarithromycin > HMR 3004 > HMR 3647, Among the species tested, Mycobacterium bovis BCG, M. ulcerans, M. avium, and M. par atuberculosis were moderately susceptible to HMR 3004 and HMR 3647 (MICs at pH 7.4, less than or equal to 5.0 and less than or equal to 20.0 mu g/ml, respectively, versus less than or equal to 1.25 mu g/ml for clarithromycin) , whereas M. tuberculosis, M. africanum, M. bovis, and M. simiae were resis tant (MICs, greater than or equal to 10.0 and greater than or equal to 40.0 mu g/ml, respectively, at pH 7.4), Although not more active than clarithro mycin in vitro, the high level of intracellular accumulation of the two ket olides inside phagocytes warrants further screening in experimental animal models.