Objectives We aimed to assess the effectiveness and nephrotoxicity of polymyxin B in critically ill patients with nosocomial pneumonia and to evaluate the utility of its therapeutic drug monitoring (TDM). Methods We retrospectively analyzed patients who received polymyxin B treatment for ≥48 h since the establishment of polymyxin B TDM in a 26‐bed tertiary referral intensive care unit. Univariate and multivariate analyses were conducted to assess the variables associated with polymyxin B effectiveness and nephrotoxicity. Results A total of 62 patients were enrolled. Most (56.5%) of the patients performed TDM, 54.3% of them reached the therapeutic target of area under curve across 24 h at steady state (AUCss,24h) of 50–100 mg h L−1, and 10 patients had an AUCss,24h value of <50 mg h L−1. Thirty‐six (58.1) and 31 (50.0%) patients had favorable clinical and microbiological responses, respectively. Reaching the therapeutic target of AUCss,24h (odds ratio [OR] = 13.15, p = 0.015), a favorable microbiological response (OR = 40.80, p = 0.00), and complicated with septic shock (OR = 0.12, p = 0.021) were independently associated with favorable clinical outcomes of polymyxin B treatment. The incidence of acute kidney injury (AKI) was 45.2%. A lower creatinine clearance (OR = 0.96, p = 0.008) and concomitant treatment with loop diuretics (OR = 5.93, p = 0.046) were predictive of nephrotoxicity. Conclusion Our findings show that TDM of polymyxin B is a valuable intervention, and the achievement of its optimal pharmacodynamic target can improve treatment outcome. Renal insufficiency and concomitant treatment with loop diuretics were found to be associated with the risk of nephrotoxicity.

What is known and objective: The presence of extracorporeal membrane oxygenation (ECMO) is suggested to further exacerbate the pharmacokinetics (PK) alterations that occur during critical illness. The objectives of this study were to determine the population PK model of polymyxin B in critically ill patients with or without ECMO support investigated the influence of ECMO on PK variability and to identify an optimal dosing strategy.Methods: Forty-four critically ill patients were enrolled, including eight patients with ECMO support. Eight serial serum samples were collected from each patient at steady state. The population PK was determined using NONMEM and Monte Carlo simulation was performed to evaluate the exposures of different dosing regimens. Results:The PK analyses included 342 steady-state concentrations and a twocompartment model was optimal for polymyxin B PK data modelling. In the final model, creatinine clearance (CL CR ) was the significant covariate on CL (typical value 1.27 L/h; between-subject variability 15.1%) and ECMO did not show a significant impact on the polymyxin B PK. Additionally, we found that the PK parameter estimates of patients with and without ECMO support were mostly similar. Based on Monte Carlo simulations, the dose escalation of polymyxin B in patients with increased CL CR improved the probability of achieving required exposure. For patients with CL CR ≤ 120 ml/min, a dosage regimen of 100 mg every 12 h may represent the optimal regimen at an MIC of 1 mg/L.What is new and conclusion: The impact of ECMO on the polymyxin B PK is likely to be minimal. Our study showed a potential relationship between CL CR and polymyxin B CL, and the dose of polymyxin B should be adjusted in patients with increased CL CR .