MIC and time-kill study of activities of DU-6859a, ciprofloxacin, levofloxacin, sparfloxacin, cefotaxime, imipenem, and vancomycin against nine penicillin-susceptible and -resistant pneumococci

Abstract

MIC and time-kill methods were used to test the activities of DU-6859a, ciprofloxacin, levofloxacin, sparfloxacin, cefotaxime, imipenem, and vancomycin against nine penicillin-susceptible, -intermediate, and -resistant pneumococci. The MIC of penicillin for penicillin-susceptible strains was 0.016 μg/ml, those for intermediate strains were 0.25 to 1.0 μg/ml, and those for resistant strains were 2.0 to 4.0 μg/ml. Of the four quinolones tested, DU-6859a had the lowest MIC (0.064 μg/ml), followed by sparfloxacin (0.25 to 0.5 μg/ml) and levofloxacin and ciprofloxacin (both 1.0 to 4.0 μg/ml). Vancomycin inhibited all strains at MICs of 0.25 to 0.5 μg/ml. The MICs of imipenem and cefotaxime for penicillin-susceptible, -intermediate, and -resistant strains were 0.004 to 0.008, 0.008 to 0.032, and 0.25 μg/ml and 0.016, 0.125 to 0.5, and 2.0 μg/ml, respectively. DU-6859a was bactericidal at eight times the MICs (0.5 μg/ml) for seven of the nine strains after 4 h and bactericidal for all nine strains after 6 h at eight times the MICs and after 12 h at two times the MICs. By comparison, sparfloxacin, the next most active quinolone, was uniformly bactericidal at two times the MICs only after 24 h, with little activity after 2 h. Levofloxacin and ciprofloxacin were bactericidal against all strains after 12 h at eight times the MICs and against all strains at 24 h at four times the MICs. Imipenem was bactericidal against all strains, at concentrations exceeding the MICs, after 24 h. Cefotaxime was also uniformly bactericidal only after 24 h of incubation at two times the MICs. Vancomycin, despite having uniformly low MICs for all strains irrespective of their penicillin susceptibility, was uniformly bactericidal only at two times the MICs after 24 h.