Pharmacokinetics of linezolid in critically ill patients

ABSTRACT

Introduction: Linezolid is an oxazolidinone antibiotic active against Gram-positive bacteria, and is most commonly used to treat life-threatening infections in critically ill patients. The pharmacokinetics of linezolid are profoundly altered in critically ill patients, partly due to decreased function of vital organs, and partly because life-sustaining drugs and devices may change the extent of its excretion.

Areas covered: This article is summarizes key changes in the pharmacokinetics of linezolid in critically ill patients. The changes summarized are clinically relevant and may serve as rationale for dosing recommendations in this particular population.

Expert opinion: While absorption and penetration of linezolid to tissues are not significantly changed in critically ill patients, protein binding of linezolid is decreased, volume of distribution increased, and metabolism may be inhibited leading to non-linear kinetics of elimination; these changes are responsible for high inter-individual variability of linezolid plasma concentrations, which requires therapeutic plasma monitoring and choice of continuous venous infusion as the administration method. Acute renal or liver failure decrease clearance of linezolid, but renal replacement therapy is capable of restoring clearance back to normal, obviating the need for dosage adjustment. More population pharmacokinetic studies are necessary which will identify and quantify the influence of various factors on clearance and plasma concentrations of linezolid in critically ill patients.

KEYWORDS:

• Linezolid
• critically ill patients
• pharmacokinetics
• therapeutic drug monitoring

Article highlights

• Linezolid has excellent penetration in all tissues and organs including central nervous system of critically ill patients.

• Plasma concentrations of linezolid in critically ill are subject to high interindividual variability, requiring therapeutic drug monitoring.

• Continuous venous infusion is linezolid administration method of choice in critically ill patients because it keeps therapeutic plasma concentrations more reliably.

• Severe liver failure and end-stage renal failure decrease linezolid clearance for 50% and 20%, respectively.

• Renal replacement therapy brings linezolid clearance to normal, and dosage adjustment is not necessary.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.