Int J Antimicrob Agents. 2023 Oct 13:107006. doi: 10.1016/j.ijantimicag.2023.107006. Online ahead of print.
Hepatic impairments increase the risk of drug overexposure in septic patients. However, there is a lack of effective indicators to predict overexposure risks. The indocyanine green (ICG) clearance test is a helpful method for dynamically assessinghepatic function and perfusion. The objective of this study was to investigate whether the ICG test could serve as a potential predictor of the linezolid trough concentration (Cmin), and we compared its efficacy with that of conventional liver function markers. Thirty-five consecutive septic patients treated with linezolid were subgrouped into either linezolid Cmin≤7μg/mL or linezolid Cmin>7μg/mL. Correlations between the linezolid Cmin and ICG-PDR (plasma disappearance rate), ICG-R15 (retention ratio after 15 minutes), and other traditional indicators were analyzed by the Spearman’s rank test. We employed a multivariable regression model to discern factors contributing independently to overexposure. Statistical differences were observed between groups for the acute physiology and chronic health evaluation (APACHE) II score (p=0.031), sepsis organ failure assessment (SOFA) score (p=0.018), creatinine clearance rate(CCR) (p=0.003), thrombocytes (p=0.039), lactate (p=0.003), ICG-PDR (p<0.001), and ICG-R15 (p<0.001). Moreover, linezolid Cminwas correlated with ICG-PDR (rho=-0.628, p<0.001), ICG-R15 (rho= 0.676, p<0.001), and CCR (rho=-0.503, p=0.002). We identified ICG-PDR as an independent predictor of linezolid overexposure, with an optimal cut-off value of 17.70%/minute (93.3% sensitivity, 85.0% specificity, p < 0.001). This pilot clinical trial represents the first investigation of the potential of the ICG test to predict linezolid overexposure in septic patients.