Linezolid-Induced Lactic Acidosis: Avoiding Concomitant Use With Metformin and Monitoring Linezolid Trough Concentration

Abstract

Objective: Serum lactic acidosis has been reported as a serious adverse effect associated with linezolid. This study aims to explore the risk factors of linezolid-induced lactic acidosis.

Methods: Patients admitted to a 3600-bed university hospital, who received linezolid treatment and had at least one steady-state concentration of linezolid, were retrospectively reviewed to analyze the incidence of linezolid-induced lactic acidosis. Meanwhile, univariate and multivariate logistic regression analyses were conducted to determine the risk factors of lactic acidosis.

Results: A total of 95 adult patients were included in the study. 18.95% (18 out of 95) of patients developed lactic acidosis during linezolid treatment. Importantly, patients who concurrently used linezolid and metformin had a high risk of developing lactic acidosis (90.9%, 10 out of 11). After excluding these patients from the original database, 9.52% (8 out of the 84) of the patients developed lactic acidosis. In the population not receiving concurrent metformin treatment, univariate analysis showed that patients who developed lactic acidosis had higher linezolid C_min and serum creatinine levels or lower creatinine clearance, and multivariate analysis showed that C_min (OR: 1.114; 95% CI: 1.012–1.226; p = 0.027) was an independent risk factor for lactic acidosis.

Conclusion: The concurrent use of linezolid and metformin raises the risk of lactic acidosis. Therapeutic drug monitoring of linezolid based on C_min is recommended for decreasing the risk of lactic acidosis during linezolid treatment.