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 48hours of therapy. Pharmacokinetic parameters were gathered from previously published studies. The AUC/MIC ratio of at least 400 and an average of AUC at > 700mgh/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 ≤1mg/L, and definite therapy with actual MIC of 1mg/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.