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 beta-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.