Influence of renal function on trough serum concentrations of piperacillin in intensive care unit patients.
OBJECTIVE
To explore the effects of renal function estimated by measured creatinine clearance (Cl(CR)) on trough serum concentration (C(min)) of piperacillin given to critically ill patients.


METHODS
Prospective observational study.


METHODS
An intensive care unit and research ward in a university hospital.


METHODS
Seventy critically ill patients, including 22 with severe trauma.


METHODS
All subjects received an intravenous infusion of piperacillin 4 g three times (n = 61) or four times (n = 9) per day. Piperacillin C(min) values were determined 24 h after treatment started and compared to the French breakpoint defining antibiotic susceptibility against Enterobacteriaceae (8 mg/l) or Pseudomonas sp. (16 mg/l).


RESULTS
Median (range) piperacillin C(min) was 11.9 (< 1-156.3) mg/l, with a great variability among patients. Although the median value was close to the breakpoints, sub-therapeutic plasma levels were frequently observed. Piperacillin C(min) was lower than the breakpoint for Enterobacteriaceae in 37% of patients, and lower than the breakpoint for P. aeruginosa in 67% of them. A strong relationship was observed between piperacillin C(min) and Cl(CR): the higher the Cl(CR,) the lower the piperacillin C(min )in serum. For patients with a Cl(CR) < 50 ml/min, enough piperacillin C(min) was achieved in most patients with 12 g piperacillin per day. For patients with higher Cl(CR) values, a piperacillin daily dose of 16 g or more may be warranted.


CONCLUSIONS
In critically ill patients, therapeutic monitoring must be part of the routine, and knowledge of Cl(CR) value may be useful for the choice of adequate initial piperacillin dosing.
Conil
Jean-Marie
JM
Laboratoire de Cinétique des Xénobiotiques, UMR 181 Physiopathologie et Toxicologie Expérimentale, Faculté des Sciences Pharmaceutiques de Toulouse, Toulouse, France. conil.jm@chu-toulouse.fr
Georges
Bernard
B
Mimoz
Olivier
O
Dieye
Eric
E
Ruiz
Stéphanie
S
Cougot
Pierre
P
Samii
Kamran
K
Houin
Georges
G
Saivin
Sylvie
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood*; D003422:Critical Care / Q000379:methods; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010878:Piperacillin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D003404:Creatinine; D010878:Piperacillin