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Antimicrobial Agents and Chemotherapy, October 2003, p. 3260-3269, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3260-3269.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

In Vitro Antibacterial Potency and Spectrum of ABT-492, a New Fluoroquinolone

Angela M. Nilius,* Linus L. Shen, Dena Hensey-Rudloff, Laurel S. Almer, Jill M. Beyer, Darlene J. Balli, Yingna Cai, and Robert K. Flamm{dagger}

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

Received 23 May 2003/ Returned for modification 16 June 2003/ Accepted 2 July 2003

ABT-492 demonstrated potent antibacterial activity against most quinolone-susceptible pathogens. The rank order of potency was ABT-492 > trovafloxacin > levofloxacin > ciprofloxacin against quinolone-susceptible staphylococci, streptococci, and enterococci. ABT-492 had activity comparable to those of trovafloxacin, levofloxacin, and ciprofloxacin against seven species of quinolone-susceptible members of the family Enterobacteriaceae, although it was less active than the comparators against Citrobacter freundii and Serratia marcescens. The activity of ABT-492 was greater than those of the comparators against fastidious gram-negative species, including Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Legionella spp. and against Pseudomonas aeruginosa and Helicobacter pylori. ABT-492 was as active as trovafloxacin against Chlamydia trachomatis, indicating good intracellular penetration and antibacterial activity. In particular, ABT-492 was more active than trovafloxacin and levofloxacin against multidrug-resistant Streptococcus pneumoniae, including strains resistant to penicillin and macrolides, and H. influenzae, including ß-lactam-resistant strains. It retained greater in vitro activity than the comparators against S. pneumoniae and H. influenzae strains resistant to other quinolones due to amino acid alterations in the quinolone resistance-determining regions of the target topoisomerases. ABT-492 was a potent inhibitor of bacterial topoisomerases, and unlike the comparators, DNA gyrase and topoisomerase IV from either Staphylococcus aureus or Escherichia coli were almost equally sensitive to ABT-492. The profile of ABT-492 suggested that it may be a useful agent for the treatment of community-acquired respiratory tract infections, as well as infections of the urinary tract, bloodstream, and skin and skin structure and nosocomial lung infections.

* Corresponding author. Mailing address: R47T, AP52, Abbott Laboratories, Abbott Park, IL 60064-3537. Phone: (847) 937-7706. Fax: (847) 935-0400. E-mail: angela.nilius{at}abbott.com.

{dagger} Present address: Focus Technologies, Herndon, VA 20171.

Antimicrobial Agents and Chemotherapy, October 2003, p. 3260-3269, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3260-3269.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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