Sequential Time-Kill, a Simple Experimental Trick To Discriminate between Pharmacokinetics/Pharmacodynamics Models with Distinct Heterogeneous Subpopulations versus Homogenous Population with Adaptive Resistance

Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00788-20. doi: 10.1128/AAC.00788-20. Print 2020 Jul 22.

Abstract

Experiments were conducted with polymyxin B and two Klebsiella pneumonia isogenic strains (the wild type, KP_WT, and its transconjugant carrying the mobile colistin resistance gene, KP_MCR-1) to demonstrate that conducting two consecutive time-kill experiments (sequential TK) represents a simple approach to discriminate between pharmacokinetics/pharmacodynamics models with two heterogeneous subpopulations or adaptive resistance.

Keywords: Klebsiella pneumoniae; PK/PD model; antibiotic resistance; pharmacodynamics; polymyxin B; sequential time-kill.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / pharmacokinetics
  • Anti-Bacterial Agents* / pharmacology
  • Colistin / pharmacokinetics
  • Colistin / pharmacology
  • Drug Resistance, Bacterial* / genetics
  • Klebsiella Infections* / drug therapy
  • Klebsiella pneumoniae / genetics
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Colistin