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. Design: Prospective observational study. Setting: An intensive care unit and research ward in a university hospital. Patients: Seventy critically ill patients, including 22 with severe trauma. Interventions: 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.