Piperacillin‐tazobactam dosing in anuric acute kidney injury patients receiving continuous renal replacement therapy

Abstract

AbstractIntroduction: To determine appropriate dosing of piperacillin‐tazobactam in critically ill patients receiving continuous renal replacement therapy (CRRT).Methods: The databases of PubMed, Embase, and ScienceDirect were searched. We used the Medical Subject Headings of “piperacillin‐tazobactam,” “CRRT,” and “pharmacokinetics” or related terms or synonym to identify the studies for reviews. A one‐compartment pharmacokinetic model was conducted to predict piperacillin levels for the initial 48 h of therapy. The pharmacodynamic target was 50% of free drug level above the minimum inhibitory concentration (MIC) and 4 times of the MIC. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose.Results: Our simulation study reveals that the dosing regimen of piperacillin‐tazobactam 12 g/day is appropriate for treating Pseudomonal infection with KDIGO recommended effluent rate of 25–35 mL/kg/h. The MIC values of each setting were an important factor to design piperacillin‐tazobactam dosing regimens.Conclusion: The Monte Carlo simulation can be a useful tool to evaluate drug dosing in critically ill acute kidney injury patients receiving CRRT when limited pharmacokinetic data are a concern. Clinical validation of these results is needed.