Comparative analysis of lactic acidosis induced by linezolid and vancomycin therapy using cohort and case-control studies of incidence and associated risk factors

Eur J Clin Pharmacol. 2018 Apr;74(4):405-411. doi: 10.1007/s00228-017-2377-1. Epub 2017 Dec 8.


Purpose: Lactic acidosis is a rare complication of linezolid (LZD) therapy, and its incidence and risk factors remain unknown. This study aimed to compare the incidence of LZD-associated lactic acidosis (LALA) and vancomycin (VAN)-associated lactic acidosis (VALA) and investigate the risk factors for LALA.

Methods: We performed a retrospective cohort study using propensity score-matched analyses comparing the incidence of lactic acidosis between LZD and VAN therapy. We included adult patients administered LZD or VAN between April 2014 and March 2016 and extracted patient baseline data. In a case-control study, we identified the risk factors of lactic acidosis in patients treated with LZD.

Results: We identified 94 and 313 patients who were administered LZD and VAN, respectively. The incidence of lactic acidosis after LZD and VAN therapy was 10.6 and 0.3%, respectively. After propensity score-matched analyses, the incidence of lactic acidosis with LZD therapy was significantly higher than that with VAN therapy [10.0% (8/80) vs. 0% (0/80), respectively; risk difference, 0.1; 95% confidence interval (CI), 0.03-0.17; p = 0.004]. In a case-control study, 10 patients with LALA were matched to 20 non-lactic acidosis patients by age and sex. Patients with LALA were more likely to have renal insufficiency than non-lactic acidosis patients that were in the univariate analysis (odds ratio, 7.4; 95% CI, 1.0-84.4; p = 0.02).

Conclusions: This study indicates that LALA occurs more frequently than VALA does and is associated with renal insufficiency. Therefore, close monitoring of kidney function and serum lactate is recommended during LZD therapy.

Keywords: Linezolid-associated lactic acidosis; Propensity score-matched analysis; Renal insufficiency; Vancomycin-associated lactic acidosis.

Publication types

  • Comparative Study

MeSH terms

  • Acid-Base Equilibrium / drug effects*
  • Acidosis, Lactic / chemically induced*
  • Acidosis, Lactic / diagnosis
  • Acidosis, Lactic / epidemiology
  • Acidosis, Lactic / physiopathology
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Biomarkers / blood
  • Chi-Square Distribution
  • Comorbidity
  • Female
  • Humans
  • Incidence
  • Lactic Acid / blood
  • Linezolid / adverse effects*
  • Male
  • Middle Aged
  • Odds Ratio
  • Prognosis
  • Propensity Score
  • Renal Insufficiency / epidemiology
  • Renal Insufficiency / physiopathology
  • Retrospective Studies
  • Risk Factors
  • Vancomycin / adverse effects*


  • Anti-Bacterial Agents
  • Biomarkers
  • Lactic Acid
  • Vancomycin
  • Linezolid