CONCENTRATION-DEPENDENT KILLING OF ANTIBIOTIC-RESISTANT PNEUMOCOCCI BY THE METHOXYQUINOLONE MOXIFLOXACIN

The in-vitro activity of the methoxyquinolone moxifloxacin (Bay 12-803 9) was compared with that of ciprofloxacin, levofloxacin, norfloxacin, ofloxacin and sparfloxacin against 220 pneumococcal isolates. Moxiflo xacin was more active than the comparator quinolones against all strai ns including 60 strains intermediately susceptible to penicillin, 60 s trains resistant to penicillin and 40 strains resistant to the macroli des. When the activity of the moxifloxacin was compared with that of o ral beta-lactams, macrolides and azalides used to treat respiratory in fections, the drug was as active as penicillin, co-amoxiclav and cefur oxime against penicillin-susceptible strains and as active as clarithr omycin and erythromycin against macrolide-susceptible strains. The dru g was more active than any oral beta-lactam agent against intermediate or fully penicillin-resistant strains and more active than any of the macrolides against macrolide-resistant strains. In time-kill assay st udies, moxifloxacin showed concentration-dependent killing at about th e MIC. The mean log(10) reduction in colony count for nine strains eac h tested in triplicate was 1.2 log(10) after 6 h of incubation at 2 x MIC of moxifloxacin. The log(10) killing at 6 h increased to 2.74 log( 10) at 4 x MIC, 3.75 log(10) at 8 x MIC and 4.17 log(10) at 16 x MIC. Because of the enhanced potency of this quinolone against pneumococci, concentrations of 8 x MIC50 were achieved at 0.48-0.96 mg/L. These da ta suggest that orally administered moxifloxacin is likely to be highl y active at physiological concentrations against penicillin- and macro lide-resistant pneumococci.