DC-159a yielded MICs of <or=1 mug/ml against 316 strains of both quinolone-susceptible and -resistant pneumococci (resistance was defined as a levofloxacin MIC >or=4 microg/ml). Although the MICs for DC-159a against quinolone-susceptible pneumococci were a few dilutions higher than those of gemifloxacin, the MICs of these two compounds against 28 quinolone-resistant pneumococci were identical. The DC-159a MICs against quinolone-resistant strains did not appear to depend on the number or the type of mutations in the quinolone resistance-determining region. DC-159a, as well as the other quinolones tested, was bactericidal after 24 h at 2x MIC against 11 of 12 strains tested. Two of the strains were additionally tested at 1 and 2 h, and DC-159a at 4x MIC showed significant killing as early as 2 h. Multistep resistance selection studies showed that even after 50 consecutive subcultures of 10 strains in the presence of sub-MICs, DC-159a produced only two mutants with maximum MICs of 1 microg/ml.