Efficacies of ABT-773, a new ketolide, against experimental bacterial infections

ABT-773 is a novel ketolide effective against antibacterial-resistant respi ratory tract pathogens. The pharmacokinetic profile of ABT-773 was studied in rats and consisted of a mean peak concentration in plasma of 1.07 mug/ml and an area under the concentration-time curve (AUC) of 12.03 mug (.) h/ml when the compound was delivered at a dose of 25 mg/kg of body weight. It c oncentrated in rat lung tissue, with a lung tissue-to-plasma ratio of 29 ba sed on the AUC. In acute systemic infections in mice, ABT-773 showed effica cy against macrolide-susceptible strains of Staphylococcus aureus, Streptoc occus pneumoniae, S. pyogenes, and Listeria monocytogenes. Additionally, AB T-773 improved the survival of mice infected with resistant S. pneumoniae c ontaining either the ermB gene, the mefE gene, or altered penicillin bindin g protein genes. In a rat lung model of infection, ABT-773 demonstrated 50% effective doses lower than those of comparator macrolides when evaluated a gainst the following strains of S. pneumoniae: a macrolide-lincosamide-stre ptogramin B-susceptible strain, an ermB strain, and an mefE strain. ABT-773 was also effective against Haemophilus influenzae lung infections in rats. Thus, ABT-773 may prove to be a useful new antibacterial agent for the tre atment of respiratory tract infections.