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INT-009 Pharmacokinetics of linezolid and meropenem in intensive care unit patients receiving continuous renal replacement therapy
  1. IKT Gilcher
  1. Department of Pharmacy, Johannes Gutenberg University Medical Center

Abstract

Background Intensive care unit (ICU) patients often suffer from infections and acute renal failure and might need continuous renal replacement therapy commonly applied by veno-venous hemodialysis (CVVHD) or hemodiafiltration (CVVHDF). In this case there are no dosage recommendations in the product informations of antibiotics and literature data are scarce. The risk for therapy failure, development of resistance and adverse drug effects is elevated.

Purpose Aim of the presented study was to find out if standard therapy of Linezolid (LZ) and Meropenem (MP) results in adequate plasma levels in surgical ICU patients receiving CVVHD(F).

Materials and Methods Surgical ICU patients receiving CVVHD(F) and 600 mg LZ b.i.d. and/or 1 g MP t.i.d. were enrolled in the study. We determined steady state plasma levels throughout one dosing interval by high-performance liquid chromatography with UV/Vis-detection. Using the resulting plasma level curve essential pharmacokinetic parameters for therapy rating were calculated, for example time of dosing interval in which plasma level exceeds minimal inhibitory concentration of the bacteria (t >MIC) or area under the inhibitory curve (AUIC).

Results 30 ICU patients were enrolled in the study. 80% of LZ patients with CVVHD(F) didn’t reach target AUIC. On the other hand 15% of LZ patients had elevated plasma levels resulting in overdose. 17 of 20 MP patients (85%) showed adequate plasma levels, 3 were overdosed as a result of 5-fold extended elimination half-life.

Conclusions LZ is underdosed in critically ill patients receiving CVVHD(F). Dose adjustment to 600 mg t.i.d. and therapeutic drug monitoring might be useful. MP standard dose is appropriate in CVVHD(F)-patients with the possibility to reduce dose in the late phase of therapy.

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