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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,
P.
Ewing,
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.

Present address: Cubist Pharmaceuticals, Cambridge, MA
02139.

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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