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

Authors

H. J. Smith, University of Manitoba
Ayman M. Noreddin, Chapman UniversityFollow
C. G. Siemens, University of Manitoba
K. N. Schurek, University of Manitoba
J. Greisman, University of Manitoba
C. J. Hoban, University of Manitoba
D. J. Hoban, University of Manitoba
G. G. Zhanel, University of Manitoba

Document Type

Article

Publication Date

2004

Abstract

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 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.

Comments

This article was originally published in Antimicrobial Agents and Chemotherapy, volume 48, issue 9, in 2004. DOI: 10.1128/AAC.48.9.3630-3635.2004

Recommended Citation

Smith HJ, Noreddin AM, Siemens CG, et al. Designing Fluoroquinolone Breakpoints for Streptococcus pneumoniae by Using Genetics instead of Pharmacokinetics-Pharmacodynamics. Antimicrobial Agents and Chemotherapy. 2004;48(9):3630-3635. doi:10.1128/AAC.48.9.3630-3635.2004.

Copyright

American Society for Microbiology