Pharmacokinetics of short versus extended infusion meropenem dosing in critically ill patients: a pilot study

Objective: To test whether a prolonged 3-hour infusion of meropenem 500 mg achieves an equivalent proportion of time above the minimal inhibitory concentration (MIC) (VoT(MIC)) to that of meropenem 1000 mg given over 30 minutes. Design, setting and participants: A randomised crossover study in 10 critically ill patients. Method: We administered meropenem as a 1000 mg, 30-minute infusion or as a 500 mg, 3-hour infusion. We determined serial plasma concentrations for each dosing episode and performed comparisons of %T-MIC at different MICs. Outcome measures: The percentage of time that meropenem was above its MIC. Results: For low MICs (<= 2 mg/L), both regimens attained a %T-MIC >40% in all patients. For an MIC of 4 mg/L, this target was attained in all but one patient, but with an MIC of 8 mg/L, three patients in each group had a %T-MIC <40%. There was no difference in target attainment between the two regimens for MICs up to 8 mg/L. There was marked variability in the pharmacokinetic and hence the pharmacokinetic pharmacodynamic parameters between individuals. Several patients had elevated creatinine clearances and, with both regimens, their target attainment was poor. Conclusions: Meropenem at 1000 mg over 30 minutes achieved a similar %T-MIC to meropenem at 500 mg given over 3 hours. Meropenem pharmacokinetics were highly variable from individual to individual.