Designing Fluoroquinolone Breakpoints for Streptococcus pneumoniae Using Genetics instead of Pharmacokinetics/Pharmacodynamics
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.
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.
American Society for Microbiology