Influence of renal function on trough serum concentrations of piperacillin in intensive care unit patients

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.

Prospective observational study.

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

Seventy critically ill patients, including 22 with severe trauma.

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).

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.

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.