Treatment of infections caused by Gram-negative pathogens: current status on the pharmacokinetics/pharmacodynamics of parenteral and inhaled polymyxins in patients

Int J Antimicrob Agents. 2020 Dec;56(6):106199. doi: 10.1016/j.ijantimicag.2020.106199. Epub 2020 Oct 17.

Abstract

Polymyxins are increasingly used as a last resort for the treatment of infections caused by multidrug-resistant Gram-negative bacteria in patients. Over the last decade, significant progress has been made in understanding the pharmacokinetics/pharmacodynamics/toxicodynamics (PK/PD/TD) of parenteral and inhaled polymyxins. This mini-review provides an overview of polymyxin chemistry, different dose definitions, and the latest research on their clinical use, toxicities, and PK/PD after intravenous and inhalation administration. Optimising the PK/PD/TD of polymyxins in patients is critical to maximise their efficacy while minimising toxicities and the emergence of resistance.

Keywords: Critically ill patients; Cystic fibrosis; Pharmacokinetics/pharmacodynamics; Safety; Toxicodynamics; Ventilator-associated pneumonia.

Publication types

  • Review

MeSH terms

  • Administration, Inhalation
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Critical Illness
  • Drug Resistance, Multiple, Bacterial / physiology
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Pneumonia, Ventilator-Associated / drug therapy
  • Polymyxins / administration & dosage
  • Polymyxins / pharmacokinetics*
  • Polymyxins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Polymyxins