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

To test whether a prolonged 3-hour infusion of meropenem 500mg achieves an equivalent proportion of time above the minimal inhibitory concentration (MIC) (%TMIC) to that of meropenem 1000mg given over 30 minutes.

A randomised crossover study in 10 critically ill patients.

We administered meropenem as a 1000mg, 30-minute infusion or as a 500mg, 3-hour infusion. We determined serial plasma concentrations for each dosing episode and performed comparisons of %TMIC at different MICs.

The percentage of time that meropenem was above its MIC.

For low MICs (≤2 mg/L), both regimens attained a %TMIC >40% in all patients. For an MIC of 4mg/L, this target was attained in all but one patient, but with an MIC of 8mg/L, three patients in each group had a %TMIC <40%. There was no difference in target attainment between the two regimens for MICs up to 8mg/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.

Meropenem at 1000mg over 30 minutes achieved a similar %TMIC to meropenem at 500mg given over 3 hours. Meropenem pharmacokinetics were highly variable from individual to individual.