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


CONCLUSIONS
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.
Dahyot-Fizelier
Claire
C
Inserm ERI-23, Poitiers, France.
Lefeuvre
Sandrine
S
Laksiri
Leila
L
Marchand
Sandrine
S
Sawchuk
Ronald J
RJ
Couet
William
W
Mimoz
Olivier
O
D000368:Aged; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001202:Ascitic Fluid / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016638:Critical Illness / Q000628:therapy; D005260:Female; D006801:Humans; D015378:Imipenem / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D017551:Microdialysis / Q000379:methods*; D008875:Middle Aged; D008956:Models, Chemical; D010538:Peritonitis / Q000188:drug therapy / Q000378:metabolism*; D012720:Severity of Illness Index
D000900:Anti-Bacterial Agents; D015378:Imipenem
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