In vitro pharmacodynamic activities of ABT-492, a novel quinolone, compared to those of Levofloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

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 mug/ml); beta-lactamase-positive and beta-lactamase-negative Haemophilus influenzae strains (MICs ranging from 0.000313 to 0.00125 mug/ml); and beta-lactamase-positive and beta-lactamase-negative Moraxella catarrhalis strains (MICs ranging from 0.001 to 0.0025 mug/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.