Background The appropriate dosing of imipenem for critically ill AKI patients undergoing CRRT remains scarce. Purpose This study aimed to (1) gather the available published pharmacokinetic studies conducted in septic patients receiving continuous renal replacement therapy (CRRT) and (2) to define the optimal imipenem dosing regimens in these populations via Monte Carlo simulations. Methods The databases of PubMed, Embase, and ScienceDirect were searched from inception to May 2020. We used the Medical Subject Headings of “Imipenem,” “CRRT,” and “pharmacokinetics” or related terms or synonym to identify the studies for systematic reviews. A one-compartment pharmacokinetic model was conducted to predict imipenem levels for the initial 48 h of therapy. The pharmacodynamic target was 40% of free drug level above 4 times of the MIC (40% fT > 4 MIC). The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. Results Eleven articles were identified and included for our systematic review. The necessary pharmacokinetic parameters such as the volume of distribution and the CRRT clearance were mentioned in 100 and 90.9%, respectively. None of the current studies reported the complete necessary parameters. A regimen of 750 mg q 6 h was the optimal dose for the predilution-CVVH and CVVHD modality with two effluent rates (25 and 35 mL/kg/h) for the pharmacodynamic target of 40% fT > 4MIC. Conclusions None of the current studies showed the complete necessary pharmacokinetic parameters for drug dosing. Pharmacodynamic target significantly contributed to imipenem dosing regimens in these patients. Different effluent rates and types of CRRT had minimal impact on dosing regimens. Clinical validation of the recommendation is necessary.

<b><i>Introduction:</i></b> The optimal meropenem dosing regimens in critically ill patients receiving continuous renal replacement therapy (CRRT) based on pharmacokinetic and pharmacodynamic (PD) concepts are not well established. This study aimed to (1) gather the available published pharmacokinetic studies conducted in septic patients receiving CRRT and (2) to define the optimal meropenem dosing regimens in these populations via Monte Carlo simulations. <b><i>Methods:</i></b> We used Medical Subject Headings “meropenem,” “continuous renal replacement therapy,” and “pharmacokinetics” or related terms to identify studies for systematic review. A one-compartment pharmacokinetic model was conducted to predict meropenem levels for the initial 48 h of therapy. The PD targets were 40% of free drug above a threshold of 1 times the minimum inhibitory concentration (MIC) (40% fT &gt; MIC), 4 times the MIC (40% fT &gt; 4MIC), and an additional target of free drug level above 1 times MIC 100% of the time (fT &gt; MIC). The dose that achieved at least 90% of the probability of target attainment (PTA) was defined as an optimal dose. <b><i>Results:</i></b> Twenty-one articles were included for our systematic review. The necessary pharmacokinetic parameters such as volume of distribution and CRRT clearance were cited in 90.5 and 71.4% of articles, respectively. None of the published studies reported completed necessary parameters. A regimen of 750 mg q 8 h was found to be the optimal dose for pre-dilution continuous venovenous hemofiltration and continuous venovenous hemodialysis modality using two effluent rates (25 and 35 mL/kg/h) which achieved the PD target of 40% fT &gt; 4MIC. <b><i>Conclusion:</i></b> None of the published studies showed the necessary pharmacokinetic parameters. PD target significantly contributed to meropenem dosage regimens in these patients. Differing effluent rates and types of CRRT shared similar dosing regimens. Clinical validation of the recommendation is suggested.