Evaluation of recommended doses of meropenem in patients with augmented renal clearance, a prospective observational study

Abstract

Aim: Augmented Renal Clearance (ARC) is a common phenomenon among critically ill patients and create sub-therapeutic concentrations of antibiotics, due to an increase in renal clearance of them. We evaluated the Pharmacokinetic and Pharmacodynamic (PK/PD) properties of recommended doses of meropenem in critically ill patients with ARC. Methods: Adult critically ill patients with confirmed ARC, based on 12-hour Creatinine Clearance (CrCl) ([?]130 ml/min/1.73 m2), who received standard doses of meropenem enrolled. Two blood samples were gathered from each participant, at the steady-state time, to determination of peak and trough concentrations. Serum concentrations of meropenem were measured by High-Performance Liquid Chromatography (HPLC) with UltraViolet (UV) detector. Results: From eighteen paired samples (peak and trough concentrations) that were obtained from 16 critically ill patients, peak concentrations were significantly lower in group 1 (received meropenem 1g every 8 hours) than group 2 (received meropenem 2g every 8 hours) (mean ±SD, 5.95 ±3.39 μg/mL vs. 11.93± 4.18 μg/mL, respectively, p= 0.005). Trough concentration were sub-threshold (< 2 μg/mL) in 10 patients of group 1 (83.3%) and 3 patients of group 2 (50%). ft > MIC [?] 50% was achieved in 83.3% of patients in both groups whereas 16.6% of patients of group 1 and 33.3% of patients of group 2 had ft> MIC= 100%. Conclusion: ARC is an essential cause of sub-therapeutic concentrations of meropenem in critically ill patients, and higher than the recommended doses of meropenem administered as an intermittent infusion may be necessary to achieve the PD targets and improve efficacy.

Pharmacokinetics, Pharmacodynamics, and Dosing Considerations of Novel β-Lactams and β-Lactam/β-Lactamase Inhibitors in Critically Ill Adult Patients: Focus on Obesity, Augmented Renal Clearance, Renal Replacement Therapies, and Extracorporeal Membrane Oxygenation

“…Similarly, although MEVs’ PKs were not described for an ARC setting, extrapolation from meropenem use among ICU patients with ARC might be considered. Different reports have highlighted reduced meropenem concentrations in such settings, coupled with required regimens’ modifications to attain a PD target [ 60 , 72 , 73 , 74 ]. Moreover, keeping in mind the predominant renal CL of vaborbactam, studies are therefore required to characterize ARC effects on MEV in terms of not only altered PK/required dosage adjustments, but also retained efficacy.…”