Pharmacokinetics and total elimination of meropenem and vancomycin in intensive care unit patients undergoing extended daily dialysis

Objective: Extended daily dialysis (EDD) combines the advantage of both intermittent hemodialysis and continuous renal replacement therapy: excellent detoxification accompanied by cardiovascular tolerability. The aim of this study was to evaluate pharmacokinetics of meropenem and vancomycin in critically ill patients with renal failure undergoing EDD. Design: Prospective clinical study. Setting: Surgical intensive care unit in a tertiary care center. Patients: We studied intensive care patients with anuric acute renal failure being treated with EDD and receiving meropenem (n = 10) or vancomycin (n = 10) therapy. Interventions: The antibiotics were administered 6 hrs (1.0 g meropenem) or 12 hrs (1.0 g vancomycin) before EDD was started in order to study the pharmacokinetics before and during EDD. In addition to the application of different methods to calculate pharmacokinetic parameters, the total dialysate concentration of both drugs was measured. Results: Based on the amount of the drug recovered from the collected spent dialysate, the fraction of drug removed by one dialysis treatment was 18% for meropenem and 26% for vancomycin. Dosing regimes for intermittent hemodialysis and continuous renal replacement therapy cannot be used for critically ill patients treated with EDD. Conclusion: Our data suggest that patients treated with EDD by means of a high-flux dialyzer (polysulphone; surface area, 1.3 m(2); blood and dialysate flow, 160 mL/min; EDD time, 480 mins) and current dosing regimens run the risk of being significantly underdosed, which may have detrimental effects on critically ill patients with life-threatening infections. The exact dose has to be tailored according to weight and severity of illness as well as the current minimal inhibitory concentration against the incriminated bacteria. Whenever possible, therapeutic drug monitoring should be performed.