Pharmacokinetics of meropenem in intensive care unit patients receiving continuous veno-venous hemofiltration or hemodiafiltration

Objective: To evaluate an intravenous meropenem dosage regimen in adult int ensive care patients with acute renal failure treated by continuous renal r eplacement therapy. Design: A prospective, clinical study. Setting: General intensive care unit of a university hospital. Patients: Ten critically ill adult patients being treated with meropenem an d receiving continuous veno-venous hemofiltration (hemofiltration rates, 1- 2 L/hr) (n = 5) or continuous venovenous hemodiafiltration (hemofiltration rates, 1-1.5 L/hr; dialysis rates, 1-1.5 L/hr) (0 = 5) via a polyacrylonitr ile hollow fiber 0.9-m(2) filter. Interventions: Patients received a meropenem dose of 1 g iv every 12 hrs as a 5-min bolus. Measurements and Main Results: Meropenem concentrations were measured bit h igh-performance liquid chromatography in serum taken at timed intervals and in ultrafiltrate/dialysate to determine serum concentration-time profiles, derive pharmacokinetic variable estimates, and determine sieving coefficie nts and filter clearances The serum concentrations were examined to see whe ther they were above the minimum inhibitory concentrations (MICs) for patho gens that may be encountered in intensive care patients. Serum concentratio ns exceeded 4 mg/L (MIC90 for Pseudomonas aeruginosa) during 67% of the dos age period in all patients. Sub-MIC90 concentrations were obtained in three patients immediately before treatment and in one patient 12 hrs after trea tment. Mean (SD) (n = 10) pharmacokinetic variable estimates were as follow s: elimination half-life, 5.16 hrs (1.83 hrs); volume of distribution, 0.35 L/kg (0.10 L/kg); and total clearance, 4.30 L/hr (1.38 L/hr). A sieving co efficient of 0.93 (0.06) (n = 9) indicated free flow across the filter. The fraction cleared by the extracorporeal route was 48% (13%) (n = 9), which is clinically important. Conclusions: A meropenem dose of 1 g iv every 12 hrs provides adequate seru m concentrations in the majority of patients receiving continuous veno-veno us hemofiltration or continuous venovenous hemofiltration with a 0.9-m(2) p olyacrylonitrile filter at combined ultrafiltrate/dialysate flow rates of u p to 3 L/hr. A lower dose would not be sufficient for the empirical treatme nt of potentially life-threatening infections in all patients.