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Antimicrobial Agents and Chemotherapy, September 2004, p. 3630-3635, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3630-3635.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Designing Fluoroquinolone Breakpoints for Streptococcus pneumoniae by Using Genetics instead of Pharmacokinetics-Pharmacodynamics

H. J. Smith,^1,2,* A. M. Noreddin,^1,2 C. G. Siemens,¹ K. N. Schurek,¹ J. Greisman,¹ C. J. Hoban,¹ D. J. Hoban,^1,2 and G. G. Zhanel^1,3

Department of Medical Microbiology, Faculty of Medicine, University of Manitoba,¹ Departments of Clinical Microbiology,² Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada³

Received 8 January 2004/ Returned for modification 17 March 2004/ Accepted 28 April 2004

We determined fluoroquinolone microbiological resistance breakpoints for Streptococcus pneumoniae by using genetic instead of pharmacokinetic-pharmacodynamic parameters. The proposed microbiological breakpoints define resistance as the MIC at which >50% of the isolates carry quinolone resistance-determining region mutations and/or, if data are available, when Monte Carlo simulations demonstrate a <90% chance of bacteriological eradication. The proposed microbiological resistant breakpoints are as follows (in micrograms per milliliter): gatifloxacin, >0.25; gemifloxacin, >0.03; levofloxacin, >1; and moxifloxacin, >0.12. Monte Carlo simulations of the once daily 400-mg doses of gatifloxacin and 750-mg doses levofloxacin demonstrated a high level of target attainment (free-drug area under the concentration-time curve from 0 to 24 h/MIC ratio of 30) by using these new genetically derived breakpoints.

Present address: Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, Minn.

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