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

Meropenem is a new carbapenem antibiotic with a broad spectrum of activity against Gram-positive and Gram-negative strains including β-lactamase producers. Thus, it is particularly useful in intensive care patients (pts) with septic complications due to unknown pathogens. The present study was conducted to evaluate the pharmacokinetic properties of meropenem in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH).

All pts received one single dose of 1 g meropenem intravenously. High-flux polysulfone membranes (Diafilter-30, Amicon, Ireland) were used as dialyzer. Meropenem serum concentrations as well as filtrate aliquots were determined by high-performance liquid chromatography.

Peak serum concentrations were 28.1 ± 2.7 μg/ml, trough levels 6.6 ± 1.5 μg/ml after 6 h CVVH. The post-to-pre hemodialysis ratio was 0.24 ± 0.06, total removal was 35.8 ± 10.1% and the mean difference of meropenem concentration between arterial and venous line was 23.4 ± 4.9%. The calculated pharmacokinetic parameters were: half-life 2.3 ± 0.4 h, elimination constant 0.31 ± 0.05 h^-1, AUC 118.0 ± 15.8 mg/l/h and the clearance during CVVH was 49.7 ± 8.3 ml/h. No side effects were seen.

The calculated total daily meropenem requirements in these patients with acute renal failure and CVVH was 2482 ± 321 mg. Based upon these data we conclude that patients with severe infections on CVVH can be treated effectively with 1 g meropenem every 8 h.