In vitro pharmacodynamic modelling simulating free serum concentrations of fluoroquinolones 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 fluoroquinolones and ciprofloxacin. Free (protein unbound) serum concentrations were simulated using peak serum concentrations and AUC(24), achieved after standard oral doses for treatment of community-acquired respiratory infections. Respiratory fluoroquinolones reduced the inoculum of isolates of multidrug-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, ciprofloxacin had a bacteriostatic (<3 log(10) reduction of the initial inoculum) effect, with rapid regrowth occurring over 48 h. Bacterial regrowth and the development of resistant mutants did not occur with any of the respiratory fluoroquinolones. Rapid regrowth and the development of resistant mutants, with MICs two- to eight-fold higher than the MIC before treatment, occurred with ciprofloxacin. These data suggest that the new respiratory fluoroquinolones with a free AUC(24)/MIC of 35-63 reduce the inoculum of multidrug-resistant S. pneumoniae below the level of detection without regrowth or development of resistance over 48 h. This study also demonstrated the poor activity of ciprofloxacin against S. pneumoniae.
Department of Medical Microbiology, Faculties of Medicine and Pharmacy, University of Manitoba, Canada. ggzhanel@pcs.mb.ca
G G
GG
Zhanel
M
M
Walters
N
N
Laing
D J
DJ
Hoban
D000284:Administration, Oral; D000890:Anti-Infective Agents / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D003198:Computer Simulation; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D006801:Humans; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000502:physiology
D000890:Anti-Infective Agents; D002939:Ciprofloxacin