Pharmacokinetics of linezolid in critically ill patients on continuous renal replacement therapy: Influence of residual renal function on PK/PD target attainment

J Crit Care. 2019 Apr:50:69-76. doi: 10.1016/j.jcrc.2018.11.016. Epub 2018 Nov 17.


Purpose: To assess the pharmacokinetics of linezolid in septic patients undergoing continuous renal replacement therapy (CRRT) and investigate whether residual renal function affects the probability of attaining the pharmacokinetic/pharmacodynamic (PK/PD) target.

Material and methods: Prospective study conducted in three Spanish hospitals. Linezolid concentrations were measured in plasma and effluent samples and pharmacokinetic parameters were calculated. The probability of target attainment (PTA) and the cumulative fraction of response (CFR) were calculated considering AUC24/MIC>80 and %T>MIC > 85% as the PK/PD indexes related to efficacy.

Results: In anuric patients (CrCl<10 mL/min), the contribution of extracorporeal Cl to total Cl was higher (47% vs 16%) than in patients with residual renal function (CrCl≥10 mL/min). For an MIC of 2 mg/L, AUC24/MIC>80 was achieved in >85% of the anuric patients, but in <15% of the patients with residual renal function.

Conclusions: The standard dose (600 mg q12h) ensures a moderately high probability of treatment success in anuric patients when the infection is due to microorganisms with MIC≤2 mg/L; although higher doses increase the probability of treatment success, the safety is compromised. In patients with residual renal function, the standard dose is insufficient, but 900 mg q8h provide higher probability of treatment success without compromising the safety.

Keywords: Continuous renal replacement therapy; Critically ill patients; Linezolid; Pharmacokinetic/pharmacodynamics; Residual renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Continuous Renal Replacement Therapy*
  • Creatine / metabolism
  • Critical Illness / therapy*
  • Female
  • Humans
  • Kidney / metabolism
  • Linezolid / pharmacokinetics*
  • Linezolid / therapeutic use
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Monte Carlo Method
  • Prospective Studies


  • Anti-Bacterial Agents
  • Linezolid
  • Creatine