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Journal of Antimicrobial Chemotherapy (2001) 47, 435-440
© 2001 The British Society for Antimicrobial Chemotherapy

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

George G. Zhanela,b,c,d,e,*, Michael Waltersc,d, Nancy Laingb,d and Daryl J. Hobanb,d

a Department of Medical Microbiology, Faculties of b Medicine and c Pharmacy, University of Manitoba; d Departments of Clinical Microbiology and e Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada

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 AUC24, 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 log10 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 AUC24/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.

* Correspondence address. Microbiology, Health Sciences Centre, MS673, 820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9. Tel: +1-204-787-4902; Fax: +1-204-787-4699; E-mail: ggzhanel{at}pcs.mb.ca


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