Continuous infusion versus intermittent administration of meropenem in critically ill patients

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (C-SS) was 11.9 +/- 5.0 mg/L; area under the curve (AUC) was 117.5 +/- 12.9 mg/L.h. The maximum and minimum serum concentrations of meropenem (C-max, C-min) and total meropenem clearance (CItot) for IA were 110.1 +/- 6.9 mg/L, 8.5 +/- 1.0 mg/L and 9.4 +/- 1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.