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
Ultra-Violet (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.