Indocyanine green clearance test as a predictor of linezolid overexposure in septic patients

Abstract

Hepatic impairment increases the risk of drug overexposure in septic patients. However, there is a lack of effective indicators to predict overexposure risk. The indocyanine green (ICG) clearance test is a helpful method for dynamically assessing hepatic function and perfusion. This study aimed to investigate whether the ICG test could serve as a potential predictor of linezolid trough concentration (Cmin) and to compare its efficacy with that of conventional liver function markers. A total of 35 consecutive septic patients treated with linezolid were grouped into either linezolid Cmin of ≤7 µg/mL or >7 µg/mL. Correlations between linezolid Cmin and ICG-PDR (plasma disappearance rate), ICG-R15 (retention ratio after 15 min) and other traditional indicators were analysed by Spearman's rank test. A multivariable regression model was employed to discern factors contributing independently to overexposure. Statistical differences were observed between groups for APACHE II score (P=0.031), SOFA score (P=0.018), creatinine clearance (CLCr) (P=0.003), thrombocytes (P=0.039), lactate (P=0.003), ICG-PDR (P < 0.001) and ICG-R15 (P < 0.001). Moreover, linezolid Cmin was correlated with ICG-PDR (ρ=-0.628, P < 0.001), ICG-R15 (ρ=0.676, P < 0.001) and CLCr (ρ=-0.503, P=0.002). ICG-PDR was identified as an independent predictor of linezolid overexposure, with an optimal cut-off value of 17.70%/min (93.3% sensitivity, 85.0% specificity; P < 0.001). This pilot clinical trial represents the first investigation of potential of the ICG test to predict linezolid overexposure in septic patients.