Association between Extended Meropenem Regimen and Achievement of Aggressive PK/PD in Patients Receiving Continuous Renal Replacement Therapy for Septic AKI

Abstract

Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1–2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose.

Keywords

• meropenem
• critically ill patients
• continuous renal replacement therapy
• acute kidney injury
• pharmacokinetics/pharmacodynamics analysis
• therapeutic drug monitoring