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Antimicrobial Agents and Chemotherapy, September 2001, p. 2585-2593, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2585-2593.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Efficacies of ABT-773, a New Ketolide, against Experimental Bacterial Infections

M. J. Mitten,* J. Meulbroek, M. Nukkala, L. Paige, K. Jarvis, A. Oleksijew, A. Tovcimak, L. Hernandez, J. D. Alder,dagger P. Ewing,Dagger Y. S. Or,§ Z. Ma, A. M. Nilius, K. Mollison, and R. K. Flamm

Infectious Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064-3537

Received 12 October 2000/Returned for modification 25 February 2001/Accepted 5 June 2001

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 µg/ml and an area under the concentration-time curve (AUC) of 12.03 µg · 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.

* Corresponding author. Mailing address: D47T, AP-3, Abbott Laboratories, Abbott Park, IL 60064-3537. Phone: (847) 937-8449. Fax: (847) 938-4777. E-mail: michael.j.mitten{at}abbott.com.

dagger Present address: Cubist Pharmaceuticals, Cambridge, MA 02139.

Dagger Present address: Angell Memorial Animal Hospital, Boston, MA 02139.

§ Present address: Enanta Pharmaceuticals, Cambridge, MA 02139.

Antimicrobial Agents and Chemotherapy, September 2001, p. 2585-2593, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2585-2593.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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