Association of elevated linezolid trough concentrations with hyperlactatemia in elderly patients: a multicenter observational study in China

The association between hyperlactatemia (HLA) and linezolid concentrations in elderly patients remains poorly understood. This study aimed to explore the associations among linezolid trough concentrations, HLA, and clinical outcomes in elderly patients. Elderly patients receiving linezolid treatment at four tertiary hospitals in Beijing between May 2021 and June 2023 were enrolled. Linezolid concentrations and arterial lactate levels were dynamically monitored, and risk factors for HLA and mortality were analyzed to develop a clinical prediction model. A total of 231 patients were studied, among whom 116 (50.2%) developed HLA. The median average trough concentration (C ave ) of linezolid was higher in the HLA group than in the non-HLA group (31.9 vs. 26.8 mg/L, P = 0.01). C ave of linezolid increased with age and was positively correlated with arterial lactate levels ( r = 0.766, P < 0.001) after adjusting for confounding factors. C ave of linezolid (OR = 1.225 [per 10 mg/L], P = 0.017) and respiratory failure (OR = 1.934, P = 0.022) were independently correlated with HLA, with an AUC of 0.709 (sensitivity 65.8%, specificity 72.5%). The optimal cutoff value of C ave of linezolid for predicting increased HLA risk was 22.4 mg/L. Elevated linezolid concentration was independently associated with 30-day mortality in exploratory analyses (OR = 1.029, P = 0.026). Elevated linezolid concentration was independently associated with higher arterial lactate levels, and was exploratorily associated with 30-day mortality in elderly patients. Given the observational design and the limited number of events, these findings should be considered hypothesis-generating. Routine combined monitoring of linezolid concentration and arterial lactate is recommended to guide timely dosage adjustment and reduce adverse outcomes. Chinese Clinical Trial Registry (trial registration number: ChiCTR2100045707; April 23, 2021).