In vitro susceptibility of penicillin-resistant Streptococcus pneumoniae to levofloxacin, selection of resistant mutants, and time-kill synergy studies of levofloxacin combined with vancomycin, teicoplanin, fusidic acid, and rifampin.

Among 180 clinical isolates of pneumococci, no strains were found to be resistant to levofloxacin (MIC, > or = 4 micrograms/ml) whereas 9% were resistant to ofloxacin and 7% were resistant to ciprofloxacin. Synergism was demonstrated by time-kill studies in nine of nine strains for the combination of levofloxacin and vancomycin and in six of nine strains for levofloxacin plus teicoplanin. The combinations of levofloxacin with rifampin or fusidic acid were indifferent. Resistant mutants could be selected using incremental concentrations of levofloxacin. For two of nine strains that were initially susceptible to levofloxacin, the MICs reached the resistance range (> or = 4 micrograms/ml). In contrast, ciprofloxacin and ofloxacin selected mutants from the susceptible to the resistant range more frequently (four of six and six of seven strains, respectively). These data argue for further study of levofloxacin against penicillin-resistant pneumococci.