In vitro activities of ABT-492, ciprofloxacin, levofloxacin, trovafloxacin, moxifloxacin, gatifloxacin, and gemifloxacin were compared. ABT-492 was more potent against quinolone-susceptible and -resistant grampositive organisms, had activity similar to that of ciprofloxacin against certain members of the family Enterobacteriaceae, and had comparable activity against quinolone-susceptible, nonfermentative, gram-negative organisms. Bactericidal activity of ABT-492 was also evaluated.Antimicrobial resistance continues to be problematic. Resistance rates in other U.S. studies were examined. More than 30% of Streptococcus pneumoniae clinical isolates are penicillin nonsusceptible, and approximately 25% are macrolide resistant (7, 10). In Haemophilus influenzae, ␤-lactamase-mediated ampicillin resistance is about 28% (11). In uncomplicated urinary tract infections, 10 to 20% of Escherichia coli isolates are resistant to trimethoprim-sulfamethoxazole and 33 to 40% are resistant to ampicillin (8, 13). Methicillin resistance in nosocomial Staphylococcus aureus has increased from 2.1% to 26-44%, and methicillin-resistant S. aureus (MRSA) is becoming a problem in community-acquired infections (1, 9, 22, 23).Fluoroquinolones have broad-spectrum activity. Newer quinolones demonstrate increased potency against S. pneumoniae, staphylococci, H. influenzae, and some enterococci and have a potency equivalent to that of ciprofloxacin against members of the family Enterobacteriaceae (3,5,12,15,16). In the United States, quinolone resistance remains low in S. pneumoniae and has been reported only rarely in H. influenzae (2,6,14,25).ABT-492 is a new fluoroquinolone with increased activity, compared to levofloxacin, trovafloxacin, and ciprofloxacin, against gram-positive organisms and activity similar to that of ciprofloxacin against certain gram-negative, quinolone-susceptible and -resistant organisms (20). The in vitro activities of ABT-492, moxifloxacin, gatifloxacin, gemifloxacin, levofloxacin, trovafloxacin, and ciprofloxacin were evaluated against 919 quinolone-susceptible and -resistant gram-positive and gramnegative pathogens. MIC ranges and MICs inhibiting 50% (MIC 50 ) and 90% (MIC 90 ) of the tested strains are shown in Table 1. Time-kill analyses of ABT-492, ciprofloxacin, and moxifloxacin were also performed.Clinical isolates dating from 1983 to 2000 from the Abbott culture collection and reference strains from the American Type Culture Collection (Manassas, Va.) were tested. Strains were classified as quinolone susceptible or resistant on the basis of levofloxacin or ciprofloxacin susceptibility for grampositive and gram-negative organisms, respectively, according to the interpretive criteria of the National Committee for Clinical Laboratory Standards (NCCLS) (17).ABT-492 and comparator quinolones were synthesized at Abbott Laboratories (Abbott Park, Ill.). Penicillin and oxacillin were purchased from Sigma Chemical Company (St. Louis, Mo.).MIC determinations and quality control tests were performed by the NCCLS broth mi...