European Journal of Clinical Pharmacology

, Volume 74, Issue 4, pp 405–411 | Cite as

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

  • Nobuaki MoriEmail author
  • Yoshio Kamimura
  • Yuki Kimura
  • Shoko Hirose
  • Yasuko Aoki
  • Seiji Bito
Clinical Trial



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.


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.


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).


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.


Linezolid-associated lactic acidosis Vancomycin-associated lactic acidosis Propensity score-matched analysis Renal insufficiency 



We would like to thank Editage ( for the English language editing and Publication Support.

Author’s contributions

NM, YK, and SB contributed to conception and design of the study. All authors contributed to acquisition of data and data analysis. NM mainly contributed to drafting this article. All authors contributed to the critical revision and gave final approval of the manuscript.

Compliance with ethics standards

This study was approved by the NTMC ethics committee (IRB protocol number: R16-102) and was carried out in accordance with the Declaration of Helsinki principles. The need for patient consent was waived owing to the retrospective nature of the study. Information about the study was made public through postings on facility notice boards and webpages. Patients and their representative agents had the right to refuse study participation.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of General Internal MedicineNational Hospital Organization, Tokyo Medical CenterTokyoJapan
  2. 2.Department of EmergencyNational Hospital Organization, Tokyo Medical CenterTokyoJapan
  3. 3.Department of PharmacologyNational Hospital Organization, Tokyo Medical CenterTokyoJapan

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