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Mitten, M.J. et al.

Mitten, Meulbroek, Nukkala, Paige, Jarvis, Oleksijew, Tovcimak, Hernandez, Alder, Ewing, Or, Ma, Nilius, Mollison, Flamm,

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

ABT-773 is a novel ketolide effective against antibacterial-resistant respiratory tract pathogens. The pharmacokinetic profile of ABT-773 was studied in rats and consisted of a mean peak concentration in plasma of 1.07 microg/ml and an area under the concentration-time curve (AUC) of 12.03 microg. h/ml when the compound was delivered at a dose of 25 mg/kg of body weight. It concentrated in rat lung tissue, with a lung tissue-to-plasma ratio of 29 based on the AUC. In acute systemic infections in mice, ABT-773 showed efficacy against macrolide-susceptible strains of Staphylococcus aureus, Streptococcus pneumoniae, S. pyogenes, and Listeria monocytogenes. Additionally, ABT-773 improved the survival of mice infected with resistant S. pneumoniae containing either the ermB gene, the mefE gene, or altered penicillin binding protein genes. In a rat lung model of infection, ABT-773 demonstrated 50% effective doses lower than those of comparator macrolides when evaluated against the following strains of S. pneumoniae: a macrolide-lincosamide-streptogramin 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 treatment of respiratory tract infections.[1]

References

Efficacies of ABT-773, a new ketolide, against experimental bacterial infections. Mitten, M.J., Meulbroek, J., Nukkala, M., Paige, L., Jarvis, K., Oleksijew, A., Tovcimak, A., Hernandez, L., Alder, J.D., Ewing, P., Or, Y.S., Ma, Z., Nilius, A.M., Mollison, K., Flamm, R.K. Antimicrob. Agents Chemother. (2001) [Pubmed]

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