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Mutant Prevention Concentration-Based Pharmacokinetic/Pharmacodynamic Indices as Dosing Targets for Suppressing the Enrichment of Levofloxacin-Resistant Subpopulations of Staphylococcus aureus▿

By Beibei Liang, Nan Bai, Yun Cai, Rui Wang, Karl Drlica and Xilin Zhao

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

Topics: Experimental Therapeutics
Publisher: American Society for Microbiology
OAI identifier: oai:pubmedcentral.nih.gov:3088181
Provided by: PubMed Central
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