ABT-492 is a novel
quinolone with potent activity against gram-positive, gram-negative, and atypical pathogens, making this compound an ideal candidate for the treatment of community-acquired
pneumonia. We therefore compared the in vitro pharmacodynamic activity of
ABT-492 to that of
levofloxacin, an
antibiotic commonly used for the treatment of
pneumonia, through MIC determination and time-kill kinetic analysis.
ABT-492 demonstrated potent activity against
penicillin-sensitive,
penicillin-resistant, and
levofloxacin-resistant Streptococcus pneumoniae strains (MICs ranging from 0.0078 to 0.125 micro g/ml);
beta-lactamase-positive and
beta-lactamase-negative Haemophilus influenzae strains (MICs ranging from 0.000313 to 0.00125 micro g/ml); and
beta-lactamase-positive and
beta-lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to 0.0025 micro g/ml), with MICs being much lower than those of
levofloxacin. Both
ABT-492 and
levofloxacin demonstrated concentration-dependent bactericidal activities in time-kill kinetics studies at four and eight times the MIC with 10 of 12 bacterial isolates exposed to
ABT-492 and with 12 of 12 bacterial isolates exposed to
levofloxacin. Sigmoidal maximal-effect models support concentration-dependent bactericidal activity. The model predicts that 50% of maximal activity can be achieved with concentrations ranging from one to two times the MIC for both
ABT-492 and
levofloxacin and that near-maximal activity (90% effective concentration) can be achieved at concentrations ranging from two to five times the MIC for
ABT-492 and one to six times the MIC for
levofloxacin.