To define the serum pharmacokinetics of a fixed-dose of piperacillin/tazobactam at 24, 48, and 72 hours of therapy when administered as a continuous infusion in critically ill trauma patients.
Prospective, open-label pharmacokinetic analysis.
A Shock/Trauma Intensive Care Unit in a university hospital.
Ten adult patients with a documented Pseudomonas aeruginosa or Acinetobacter baumanii infection with a cefepime minimum inhibitory concentration (MIC) greater than or equal to 4 μg/mL.
All subjects received a 4/0.5 g bolus dose of piperacillin/tazobactam over 30 minutes followed by a 16/2 g per day continuous infusion. Serum piperacillin/tazobactam concentrations were analyzed at 30 minutes after the bolus dose (Cmax) and at steady-state (Css) during the continuous infusion (24, 48, and 72 hours). Piperacillin/tazobactam serum concentrations were determined using high-performance liquid chromatography.
The median piperacillin and tazobactam Css observed during the continuous infusion were 34.22 μg/mL (interquartile range [IQR], 28.91 - 48.21) and 5.49 μg/mL (IQR, 4.29 - 7.05), respectively. The median piperacillin and tazobactam Cmax after the initial loading dose were respectively, 72.28 µg/mL (IQR, 59.46 - 84.00) and 7.83 µg/mL (IQR, 6.94 - 9.09). A total of 96.4% (27/28) of the serum piperacillin Css measured were above the minimum inhibitory concentration (MIC) of the pathogen isolated, with 85% (24/28) being at least 2 times the MIC. For isolates with a MIC ≥ 32 μg/mL, only 53.6% (15/28) of the serum piperacillin Css were above the MIC.
Although we found a wide variability in serum piperacillin/tazobactam concentrations, the administration of a 16/2 g per day dose as a continuous infusion achieves optimal pharmacokinetic parameters for commonly isolated microorganisms in critically ill trauma patients. In the presence of elevated MICs (> 16 µg/mL) more aggressive dosing of piperacillin/tazobactam or use of an alternative antimicrobial may be warranted in this patient population.