Optimal vancomycin dosing regimens for critically ill patients with acute kidney injury during continuous renal replacement therapy: A Monte Carlo simulation study

Purpose: This study aims to determine the optimal vancomycin dosing in critically ill patients with acute kidney injury receiving continuous renal replacement therapy (CRRT) using Monte Carlo simulation. Methods: A one compartment pharmacokinetic model was conducted to define vancomycin deposition for the initial 48 hours of therapy. Pharmacokinetic parameters were gathered from previously published studies. The AUC(24)/MIC ratio of at least 400 and an average of AUC(0-24) at > 700 mgh/L were utilized to evaluate efficacy and nephrotoxicity, respectively. The doses achieved at least 90% of the probability of target attainment (PTA) with the lowest risk of nephrotoxicity defined as the optimal dose. Results: The regimens of 1.75grams every 24hours and 1.5grams loading followed by 500mg every 8hours were recommended for empirical therapy of an MRSA infection with expected MIC <= 1 mg/L, and definite therapy with actual MIC of 1 mg/L. The probabilities of nephrotoxic results from these regimens were 35%. Conclusions: A higher dose of vancomycin than the current literature-based recommendation was needed in CRRT patients. (C) 2019 Elsevier Inc. All rights reserved.