High plasma linezolid concentration and impaired renal function affect development of linezolid-induced thrombocytopenia

J Antimicrob Chemother. 2013 Sep;68(9):2128-33. doi: 10.1093/jac/dkt133. Epub 2013 Apr 26.

Abstract

Objectives: Thrombocytopenia is sometimes observed during linezolid therapy. Here, we aimed to investigate the factors affecting linezolid-induced thrombocytopenia.

Methods: A prospective observational study was performed between October 2009 and February 2011; 30 patients were included. Plasma linezolid trough concentrations were measured on days 3, 7 and 14 after initial drug administration. Platelet counts and haemoglobin levels were also monitored.

Results: Thrombocytopenia occurred in 17 patients (56.7%). Median linezolid trough concentrations on day 3 were significantly higher in patients with renal impairment (creatinine clearance <60 mL/min) than in patients without renal impairment (14.7 versus 4.8 mg/L; P < 0.0001). Median linezolid trough concentrations on day 3 in patients who developed thrombocytopenia were also significantly higher than those in patients who did not (13.4 versus 4.3 mg/L, P < 0.0001). Development of thrombocytopenia occurred significantly more frequently in patients with linezolid trough concentration >7.5 mg/L (OR, 90.0; P < 0.0001) and renal impairment (OR, 39.0; P = 0.0002). The Kaplan-Meier plot showed that the median time from the initiation of therapy to development of thrombocytopenia was 11 days.

Conclusions: Patients with renal impairment are more likely to have a high plasma linezolid concentration. In addition, a high plasma linezolid concentration and renal impairment significantly affected the development of linezolid-induced thrombocytopenia. Further studies are required to evaluate whether therapeutic drug monitoring-guided dosage adjustment of linezolid decreases the adverse effects while maintaining treatment efficacy in patients with renal dysfunction.

Keywords: adverse effects; anti-MRSA agents; haematological toxicity; renal dysfunction; therapeutic drug monitoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / adverse effects*
  • Acetamides / pharmacokinetics*
  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Female
  • Humans
  • Kidney Diseases / physiopathology*
  • Kidney Function Tests
  • Linezolid
  • Male
  • Middle Aged
  • Oxazolidinones / administration & dosage
  • Oxazolidinones / adverse effects*
  • Oxazolidinones / pharmacokinetics*
  • Plasma / chemistry*
  • Prospective Studies
  • Thrombocytopenia / chemically induced*

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Linezolid