β-lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review

Clin Exp Pharmacol Physiol. 2012 Jun;39(6):489-96. doi: 10.1111/j.1440-1681.2012.05715.x.

Abstract

1. Infections and related sepsis are two of the most prevalent issues in the care of critically ill patients, with mortality as high as 70%. Appropriate antibiotic selection, as well as adequate dosing, is important to improve the clinical outcome for these patients. 2. β-Lactams are the most common antibiotic class used in critically ill sepsis patients because of their broad spectrum of activity and high tolerability. β-Lactams exhibit time-dependent antibacterial activity. Therefore, concentrations need to be maintained above the minimum inhibitory concentration (MIC) of pathogenic bacteria. β-Lactams are hydrophilic antibiotics with small distribution volumes similar to extracellular water and are predominantly excreted through the renal system. 3. Critically ill patients experience a myriad of physiological changes that result in changes in the pharmacokinetics (PK) of hydrophilic drugs such as β-lactams. A different approach to dosing with β-lactams may increase the likelihood of positive outcomes considering the pharmacodynamics (PD) of β-lactams, as well as the changes in PK in critically ill patients. 4. The present review describes the strategies for dose optimization of β-lactams in critically ill patients in line with the PK and PD of these drugs.

Publication types

  • Review

MeSH terms

  • Critical Illness / epidemiology
  • Critical Illness / therapy*
  • Dose-Response Relationship, Drug
  • Humans
  • Infusions, Intravenous
  • Sepsis / drug therapy
  • Sepsis / epidemiology
  • Sepsis / metabolism
  • beta-Lactam Resistance / drug effects
  • beta-Lactam Resistance / physiology
  • beta-Lactams / administration & dosage
  • beta-Lactams / pharmacokinetics*
  • beta-Lactams / pharmacology*

Substances

  • beta-Lactams