Kinetics of imipenem distribution into the peritoneal fluid of patients with severe peritonitis studied by microdialysis

Abstract

Background and objectives: A microdialysis study of meropenem distribution in the peritoneal fluid of patients with peritonitis has suggested that there is significant peripheral drug degradation. The aims of the present study were to investigate the plasma and peritoneal fluid pharmacokinetics of imipenem, a relatively unstable antibacterial, in patients with severe peritonitis, and to relate measured unbound concentrations to the minimum inhibitory concentrations required for susceptible and intermediately susceptible bacteria.

Methods: Microdialysis catheters were placed into the peritoneal cavity through peritoneal drains in nine critically patients. Imipenem concentrations in plasma and in peritoneal fluid were analysed using compartmental modelling.

Results: A model that considered elimination from a peripheral compartment described the data and was used to simulate steady-state concentration profiles in plasma and peritoneal fluid during various dosing regimens. Using recommended dosing regimens (500 mg every 6 hours, 1000 mg every 8 hours and 1000 mg every 6 hours), simulated unbound peritoneal fluid concentrations of imipenem in patients with severe peritonitis reached values sufficient for antibacterial effects against susceptible bacteria. However, the adequacy of regimens in patients with severe peritonitis whose infections involve intermediately susceptible bacteria is questionable.

Conclusion: The results of this study are consistent with those previously observed with meropenem and confirm the usefulness of microdialysis for assessment of peritoneal fluid distribution of antibacterials.