Pharmacokinetics of meropenem during continuous renal replacement therapy in critically ill patients

Abstract

Introduction: Early administration of effective intravenous antimicrobials is recommended for the management of the patients with sepsis. Although Meropenem (MEPM) is one of the first-line drugs in patients with sepsis because of its broad spectrum, the optimal dose in the critical care settings especially during continuous renal replacement therapy (CRRT) has not been established since therapeutic drug monitoring of MEPM has not been popular. Methods: Eighteen critically ill patients who received CRRT were enrolled in this study. One gram of MEPM was administered over 1 hour, every 12 hours, and blood samples at 1, 2, 6, 9 and 12 hours after administration were collected on day 1, 2 and 5. All samples were stored at -80°C until analysis. The measurement of the blood concentration of MEPM was performed using high performance liquid chromatography with ultraviolet detection (HPLC-UV). Results: The patients were 66.2±15.0 years old, 8 were male, their mean body weight was 71.7±20.8 kg, and their mean estimated creatinine clearance was 36.2±20.0 mL/min. CRRT was provided at 22.5 ±6.0 ml/kg/h. The peak concentration of the first administration of MEPM was 51.0±14.8 μ g/mL. All patients achieved time above minimum inhibitory concentration (TAM)> 50%, if minimum inhibition concentration (MIC) ≤4μ g/mL. Seventy eight % and 60% of the patients achieved TAM>50%, if MIC ≤8μ g/mL and ≤16μ g/mL, respectively. Conclusions: One gram of MEPM every 12 hours was an appropriate dose for the patients who received CRRT.