In vitro pharmacodynamic modelling simulating free serum concentrations offluoroquinolones against multidrug-resistant Streptococcus pneumoniae

An in vitro pharmacodynamic model was used to compare bacterial killing and the development of resistant mutants in the presence of respiratory fluoro quinolones and ciprofloxacin. Free (protein unbound) serum concentrations w ere simulated using peak serum concentrations and AUC(24), achieved after s tandard oral doses for treatment of community-acquired respiratory infectio ns. Respiratory fluoroquinolones reduced the inoculum of isolates of multid rug-resistant Streptococcus pneumoniae below the level of detection in the model at 12 h and did not allow regrowth to occur over 48 h. In contrast, c iprofloxacin had a bacteriostatic (<3 log(10) reduction of the initial inoc ulum) effect, with rapid regrowth occurring over 48 h. Bacterial regrowth a nd the development of resistant mutants did not occur with any of the respi ratory fluoroquinolones. Rapid regrowth and the development of resistant mu tants, with MICs two- to eight-fold higher than the MIC before treatment, o ccurred with ciprofloxacin. These data suggest that the new respiratory flu oroquinolones with a free AUC(24)/MIC of 35-63 reduce the inoculum of multi drug-resistant S. pneumoniae below the level of detection without regrowth or development of resistance over 48 h. This study also demonstrated the po or activity of ciprofloxacin against S. pneumoniae.