The impact of continuous renal replacement therapy on antibiotic pharmacokinetics in critically ill patients

Expert Opin Drug Metab Toxicol. 2021 May;17(5):543-554. doi: 10.1080/17425255.2021.1902985. Epub 2021 Mar 28.

Abstract

Introduction: Mortality due to severe infections in critically ill patients undergoing continuous renal replacement therapy (CRRT) remains high. Nevertheless, rapid administration of adequate antibiotic therapy can improve survival. Delivering optimized antibiotic therapy can be a challenge, as standard drug regimens often result in insufficient or excessive serum concentrations due to significant changes in the volume of distribution and/or drug clearance in these patients. Insufficient drug concentrations can be responsible for therapeutic failure and death, while excessive concentrations can cause toxic adverse events.Areas covered: We performed a narrative review of the impact of CRRT on the pharmacokinetics of the most frequently used antibiotics in critically ill patients. We have provided explanations for the changes in the PKs of antibiotics observed and suggestions to optimize dosage regimens in these patients.Expert opinion: Despite considerable efforts to identify optimal antibiotic dosage regimens for critically ill patients receiving CRRT, adequate target achievement remains too low for hydrophilic antibiotics in many patients. Whenever possible, individualized therapy based on results from therapeutic drug monitoring must be given to avoid undertreatment or toxicity.

Keywords: Aminoglycosides; acute kidney injury; antibiotics; beta-lactams; critically ill patients; glycopeptides; lipopeptides; pharmacokinetics; renal replacement therapy; sepsis.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics*
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / mortality
  • Continuous Renal Replacement Therapy*
  • Critical Illness
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods
  • Humans

Substances

  • Anti-Bacterial Agents