Elucidating the Pharmacokinetics/Pharmacodynamics of Aerosolized Colistin against Multidrug-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Mouse Lung Infection Model

Antimicrob Agents Chemother. 2018 Jan 25;62(2):e01790-17. doi: 10.1128/AAC.01790-17. Print 2018 Feb.

Abstract

The pharmacokinetics/pharmacodynamics (PK/PD) of aerosolized colistin was investigated against Acinetobacter baumannii and Klebsiella pneumoniae over 24 h in a neutropenic mouse lung infection model. Dose fractionation studies were performed over 2.64 to 23.8 mg/kg/day, and the data were fitted to a sigmoid inhibitory model. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC) in the epithelial lining fluid was the most predictive PK/PD index for aerosolized colistin against both pathogens. Our study provides important pharmacological information for optimizing aerosolized colistin.

Keywords: Acinetobacter baumannii; Gram-negative bacteria; Klebsiella pneumoniae; polymyxin; pulmonary administration; respiratory tract infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects*
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Colistin / pharmacokinetics*
  • Colistin / pharmacology*
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Klebsiella pneumoniae / drug effects*
  • Lung / microbiology
  • Mice
  • Microbial Sensitivity Tests / methods
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / microbiology

Substances

  • Anti-Bacterial Agents
  • Colistin