Telithromycin Is Active against Mycobacterium avium in Mice despite Lacking Significant Activity in Standard In Vitro and Macrophage Assays and Is Associated with Low Frequency of Resistance during Treatment

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Abstract
The activity of telithromycin, a new ketolide, was evaluated in vitro and in vivo against Mycobacterium avium complex (MAC) strains. The MIC of telithromycin for several M. aviumisolates obtained from the blood of AIDS patients ranged from 16 to >128 μg/ml (MIC at which 90% of isolates are inhibited, >128 μg/ml), and the compound did show activity in the macrophage system at concentrations greater than 8 or 16 μg/ml, but this was dependent on the MAC strain used. Telithromycin was then administered to mice infected with MAC strain 101 for 4 weeks at doses of 100, 200, or 400 mg/kg of body weight/day. Treatment with 100 and 200 mg/kg/day was bacteriostatic, but at 400 mg/kg/day telithromycin was bactericidal for MAC strains. The frequency of the emergence of resistance to telithromycin was low despite prolonged usage (12 weeks). This study demonstrates that telithromycin is active in vivo against MAC and warrants further evaluation.