Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients

Introduction: The correlation between total and free polymyxin B (PMB including PMB1 and PMB2) exposure in vivo and acute kidney injury (AKI) remains obscure. This study explores the relationships between plasma exposure of PMB1 and PMB2 and nephrotoxicity, and investigates the risk factors for PMB-induced acute kidney injury (AKI) in critically ill patients. Methods: Critically ill patients who used PMB and met the criteria were enrolled. The total plasma concentration and plasma binding of PMB1 and PMB2 were analysed by liquid chromatography–tandem mass spectrometry and equilibrium dialysis. Results: A total of 89 patients were finally included, and AKI developed in 28.1% of them. The peak concentration of PMB1 (C_max(B1)) (adjusted odds ratio (AOR) = 1.68, 95% CI 1.08–2.62, p= 0.023), baseline BUN level (AOR = 1.08, 95% CI 1.01–1.16, p= 0.039) and hypertension (AOR = 3.73, 95% CI 1.21–11.54, p= 0.022) were independent risk factors for PMB-induced AKI. The area under the ROC curve of the model was 0.799. When C_max(B1) was 5.23 μg/ml or more, the probability of AKI was higher than 50%. The ratio of PMB1/PMB2 decreased after PMB preparation entered into the body. The protein binding rate in critically ill patients indicated significant individual differences. Free C_max(B) and free C_max(B1) levels in the AKI group were significantly (p< 0.05) higher than those in the non-AKI group. Total and free concentrations of PMB in patients showed a positive correlation. Conclusions: Both the ROC curve and logistic regression model showed that C_max(B1) was a good predictor for the probability of PMB-induced AKI. Early therapeutic drug monitoring (TDM) of PMB should be considered in critically ill patients. Compared with C_min(B), C_max(B) and C_max(B1) may be helpful for the early prediction of PMB-induced AKI in critically ill patients.