title: Mutant prevention concentration-based pharmacokinetic/pharmacodynamic indices as dosing targets for suppressing the enrichment of levofloxacin-resistant subpopulations of Staphylococcus aureus.
abstract: MIC- and mutant prevention concentration (MPC)-based pharmacokinetic/pharmacodynamic (PK/PD) indices were compared for suitability as attainment targets for restricting amplification of levofloxacin-resistant mutant subpopulations. When three Staphylococcus aureus strains were examined with a hollow-fiber PK/PD model, area under the concentration-time curve over 24 h (AUC24)/MPC values of >25 and maximum concentration of drug in serum (Cmax)/MPC values of >2.2 predicted resistance outcome among different isolates with an interisolate kappa coefficient of 1. MIC-based mutant-restrictive PK/PD values varied >8-fold and exhibited only a moderate interisolate agreement (kappa coefficient of 0.5). Thus, MPC-based PK/PD indices are more suitable than MIC-based indices for predicting mutant-restricting fluoroquinolone doses when multiple bacterial isolates are considered.
authors.affiliation: Department of Clinical Pharmacology, PLA (301) General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Liang
authors.forename: Nan
authors.initials: N
authors.lastname: Bai
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Karl
authors.initials: K
authors.lastname: Drlica
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin