title: In vitro pharmacodynamic activities of ABT-492, a novel quinolone, compared to those of levofloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
abstract: 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.
authors.affiliation: Department of Pharmacy Practice, The University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Shana M
authors.initials: SM
authors.lastname: Gunderson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hayes
authors.forename: John P
authors.initials: JP
authors.lastname: Quinn
authors.forename: Larry H
authors.initials: LH
authors.lastname: Danziger
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones; D006193:Haemophilus influenzae / Q000187:drug effects*; D007700:Kinetics; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects*; D015242:Ofloxacin / Q000494:pharmacology*; D010403:Penicillin Resistance; D015363:Quinolones / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C477891:delafloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D001618:beta-Lactamases