Work

An easy-to-use predictive score for identifying patients at risk of suboptimal linezolid exposure and candidates for therapeutic drug monitoring

Year: 2025

Type: article

Abstract: • Standard linezolid dosing results in therapeutic plasma concentrations in only one-third of patients. • Sub- and supra-therapeutic linezolid exposures are associated with patient-specific factors including age, renal function, critical illness, liver disease and dose/body weight ratio. • A predictive score was developed to identify patients at high risk of out-of-range concentrations. • The score demonstrated excellent accuracy in identifying patients at risk of linezolid overexposure and had moderate performance for underexposure. • This tool supports targeted implementation of TDM to optimize linezolid dosing and improve patient outcomes. Due to the high interindividual pharmacokinetic variability, only between 34.5-57.5% patients treated with linezolid fall within its therapeutic range with standard dosing. This study aimed to develop and validate a simple-to-use predictive score to identify patients at risk of sub- or supra-therapeutic linezolid exposure who may benefit from therapeutic drug monitoring (TDM). A retrospective observational study was conducted using data from 819 patients treated with linezolid and undergoing TDM (2011-2022). Linezolid trough concentrations were classified as sub-therapeutic, therapeutic and supra-therapeutic (< 2 mg/L, between 2-7 mg/L and > 7 mg/L, respectively). A multinomial logistic regression model was used to develop a predictive score, which was externally validated in a separate cohort of 73 patients. Discrimination performance was assessed using ROC curve. Only 31.5% of patients achieved therapeutic concentrations. Median linezolid trough concentrations were 3.9 mg/L (range: 0.5–63.7 mg/L). Independent predictors of sub-therapeutic concentrations were a younger age, a low linezolid dose/body weight, augmented renal clearance and intensive care unit admission. Predictors of supra-therapeutic concentrations were a higher dose/body weight, renal impairment, and liver cirrhosis. The predictive model showed high accuracy for identifying patients at risk of supra-therapeutic exposure (AUC 82% derivation; 90% validation), while performance was moderate for underexposure (AUC 63% derivation; 49% validation). An online calculator was implemented to facilitate score use in clinical practice. The predictive score provides clinicians with an effective tool to support individualized linezolid therapy and guide TDM implementation, reducing the risk of toxicity or treatment failure.

Source: International Journal of Antimicrobial Agents

DOI: 10.1016/j.ijantimicag.2025.107661