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

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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.


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


American Society for Microbiology