Clinical pharmacokinetic/pharmacodynamic profile of linezolid in severely ill intensive care unit patients

Int J Antimicrob Agents. 2011 Oct;38(4):296-300. doi: 10.1016/j.ijantimicag.2011.05.007. Epub 2011 Jul 8.


Severely ill Intensive Care Unit (ICU) patients have an increased risk of developing multiresistant Gram-positive infections, largely due to the inappropriate use of antimicrobials. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) profile of linezolid, an antibiotic against Gram-positive infections, was characterised in eight critically ill patients admitted to the ICU. Remarkable variation amongst patients in the PK parameters of linezolid was observed, including a 5-7-fold difference in peak serum concentration (C(max)) (mean±standard deviation 15.70±6.58 mg/L) and 12-h area under the serum concentration-time curve (AUC(0-12)) (96.73±56.45 mg h/L), although the minimum inhibitory concentration (MIC) was similar amongst patients. In particular, variation amongst patients was found in the ratio of AUC(0-24)/MIC (range 31.66-216.82, mean 96.73) and the percentage of time that the serum concentration exceeded the MIC (T>MIC) (range 53.4-100%), two parameters used to predict linezolid efficacy. These variations highlight the importance of individual monitoring of linezolid PK/PD properties in critically ill patients. Furthermore, it was observed that regardless of AUC(0-24)/MIC and T>MIC values, the clinical and microbiological responses of patients were primarily affected by the individual's pathophysiological condition. In summary, these findings point to highly variable PK/PD properties of linezolid in severely ill patients, providing the rationale for targeting linezolid dosage to each individual patient's specific properties. An optimal dosage regimen based on individual PK/PD properties and pathophysiological conditions will help reduce the occurrence of resistance in Gram-positive bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / blood
  • Acetamides / pharmacokinetics
  • Acetamides / pharmacology*
  • Acetamides / therapeutic use
  • Adult
  • Aged
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Area Under Curve
  • Critical Illness
  • Drug Resistance, Multiple, Bacterial
  • Female
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / physiology
  • Gram-Positive Bacterial Infections / drug therapy
  • Gram-Positive Bacterial Infections / metabolism*
  • Humans
  • Intensive Care Units*
  • Linezolid
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Oxazolidinones / blood
  • Oxazolidinones / pharmacokinetics
  • Oxazolidinones / pharmacology*
  • Oxazolidinones / therapeutic use
  • Treatment Outcome


  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Linezolid