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    ABSTRACT: In vitro and in vivo antibacterial activities of modithromycin against Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae were examined. MICs were determined by the broth microdilution method. Experimental infection of epithelial cell line A549 was performed to compare the intracellular activity and lasting effects of the antimicrobial agents. To evaluate in vivo efficacy, the rat pulmonary infection model was used. Modithromycin had MICs of ≤ 1 mg/L against all the clinical strains of both streptococci, including erythromycin-resistant strains. In particular, the MICs of modithromycin for erm(B)- or mef(A)-carrying S. pyogenes were 16-32 times or 2-4 times lower than those of telithromycin, respectively. The MIC(90) of modithromycin for H. influenzae was 8 mg/L, which was 4 times higher than that of telithromycin. Modithromycin, as well as azithromycin, showed a lasting inhibitory effect on bacterial growth of cell-associated H. influenzae compared with telithromycin and levofloxacin after removal of the agents from the apical medium. In the pulmonary infection model, modithromycin showed greater or comparable efficacy against erm(B)-carrying S. pneumoniae and H. influenzae, respectively, than telithromycin, regardless of having an MIC that was 2 or 4 times higher for these strains. Modithromycin has the most potent anti-S. pyogenes activity of the antimicrobial agents tested. Modithromycin also has the better in vivo efficacy against S. pneumoniae and H. influenzae, which might be due to its lasting intracellular activity.
    No preview · Article · Jul 2011 · Journal of Antimicrobial Chemotherapy