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  • Title: In vitro intracellular activity and in vivo efficacy of modithromycin, a novel bicyclolide, against Legionella pneumophila.
    Author: Sato T, Tateda K, Kimura S, Ishii Y, Yamaguchi K.
    Journal: Antimicrob Agents Chemother; 2011 Apr; 55(4):1594-7. PubMed ID: 21220530.
    Abstract:
    The in vitro and in vivo activities of modithromycin, a novel bicyclolide, against Legionella pneumophila were compared with those of telithromycin, clarithromycin, azithromycin, and levofloxacin. All the test agents decreased the intracellular growth of viable L. pneumophila bacteria over 96 h of incubation in both types of cells used, A/J mouse-derived macrophages and A549 human alveolar epithelial cells, at extracellular concentrations of 4× and 16× MIC, respectively. However, when the agents were removed from the medium after exposure for 2 h, regrowth of intracellular bacteria occurred in both cell systems when they were exposed to telithromycin, clarithromycin, and levofloxacin but not when they were exposed to modithromycin and azithromycin. Once-daily administration of modithromycin at a dose of 10 mg/kg of body weight for 5 days led to a significant decrease of intrapulmonary viable L. pneumophila bacteria in immunosuppressed A/J mice. The efficacy of modithromycin was superior to the efficacies of telithromycin and clarithromycin and comparable to the efficacies of azithromycin and levofloxacin. In addition, modithromycin and azithromycin inhibited the intrapulmonary regrowth of bacteria even at 72 h after the last treatment, but telithromycin and levofloxacin did not. These results suggested that modithromycin has longer-lasting cellular pharmacokinetic features like azithromycin. In conclusion, modithromycin, as well as azithromycin, has excellent in vitro and in vivo bactericidal activities and persistent efficacy against intracellular L. pneumophila. Modithromycin should be a useful agent for treatment of pulmonary infections caused by this pathogen.
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