The activity of DC-159a, a novel orally administered fluorinated quinolone, was evaluated by reference broth microdilution or agar dilution methods against 1,149 recently collected clinical isolates from five continents. Against pathogens associated with community-acquired respiratory tract infections (CA-RTIs), the MIC(90)s were 0.12 microg/ml for Streptococcus pneumoniae, 0.015 to 0.03 microg/ml for Haemophilus influenzae, 0.03 microg/ml for Moraxella catarrhalis, and 0.12 microg/ml for beta-hemolytic streptococci. Similarly, DC-159a was potent against various types of staphylococci (MIC(90) range, 0.03 to 2 microg/ml), Enterococcus faecalis (MIC(90), 4 microg/ml), wild-type isolates of the family Enterobacteriaceae (MIC(90) range, 0.06 to 2 microg/ml), wild-type Pseudomonas aeruginosa (MIC(90), 2 microg/ml), and Acinetobacter spp. (MIC(90), 0.12 microg/ml). Fluoroquinolone-nonsusceptible organism subsets usually had elevated DC-159a MICs, but the MICs were often two- to fourfold lower than those of levofloxacin and moxifloxacin. In conclusion, DC-159a appears to possess a balanced broad spectrum of activity that exceeds the activities of the currently marketed fluoroquinolones, especially against pathogens that cause CA-RTIs.