Correlation of Meropenem Plasma Levels with Pharmacodynamic Requirements in Critically Ill Patients Receiving Continuous Veno-Venous Hemofiltration

Background: In patients with acute renal failure, the pharmacokinetics of meropenem depend on the operational characteristics of the renal replacement therapy. Dosage recommendations are based on the correlation of plasma levels with pharmacodynamic requirements. Methods: Eight critically ill patients with acute renal failure were treated by continuous veno-venous hemofiltration with a filtrate flow of 1,600 ml/h and received 500 mg of meropenem every 12 h. Plasma and hemofiltrate concentrations of meropenem at steady state were determined by HPLC. Results: Peak levels in plasma amounted to 39.5 ± 10.5 mg/l (mean ± SD) and trough levels were 2.4 ± 1.5 mg/l. The minimal inhibitory concentration (MIC) for susceptible bacteria (4 mg/l) was covered for 40% of the dosing interval or longer in all patients. The MIC for intermediately susceptible organisms (8 mg/l) was covered for 33% in 6 of the 8 patients. The elimination half-life was prolonged to 3.63 ± 0.77 h. The sieving coefficient of meropenem was 0.91 ± 0.10 and the recovery in hemofiltrate amounted to 30.9 ± 11.5% of the dose. Conclusions: A dosage of 500 mg twice daily provides appropriate serum levels for the treatment of infections caused by susceptible bacteria. A higher dosage is adequate for infections by intermediately susceptible bacteria or for renal replacement therapies with markedly higher filtrate flow rates.