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.