Hepatic and pancreatic surgeries are associated with a high risk of surgical site infections, particularly in patients with preoperative biliary drainage, which is frequently associated with bacterial colonization of bile. In this context, perioperative antibiotic prophylaxis is essential, and recent guidelines recommend the use of piperacillin/tazobactam in selected high-risk patients.
However, piperacillin, like other β-lactam antibiotics, exhibits pharmacokinetic variability that may be exacerbated during major surgery due to factors such as fluid shifts, hypoalbuminemia, and changes in volume of distribution. These alterations may result in suboptimal antibiotic exposure during the perioperative period, potentially compromising prophylactic efficacy.
Despite these concerns, standard dosing regimens remain unchanged across different types of major abdominal surgery, including hepatic and pancreatic procedures, which differ significantly in terms of duration, physiological impact, and intraoperative management.
The PROPHTAZ study is a prospective, single-center observational pharmacokinetic study designed to evaluate whether standard perioperative administration of piperacillin/tazobactam achieves predefined pharmacokinetic/pharmacodynamic (PK/PD) targets in patients undergoing hepatic or pancreatic surgery. The primary objective is to determine the proportion of patients achieving adequate PK/PD exposure during surgery. Secondary objectives include describing perioperative plasma concentrations, assessing pharmacokinetic variability, identifying factors associated with target non-attainment, and comparing outcomes between surgical subgroups.
This study aims to provide clinically relevant data to assess the adequacy of current prophylactic dosing strategies and to support potential optimization of antibiotic administration in high-risk surgical patients.
Adults > or = to 18 years old
Scheduled for major hepatic or pancreatic surgery
Receiving piperacillin/tazobactam as perioperative antibiotic prophylaxis according to guidelines
decline to participate
Known allergy of beta-lactam
The study population consists of adult patients undergoing elective hepatic or pancreatic surgery at a tertiary care university hospital (CHRU Nancy, France). Eligible patients are those receiving perioperative antibiotic prophylaxis with piperacillin/tazobactam according to current clinical guidelines, particularly in the context of preoperative biliary drainage or high risk of biliary contamination. These patients represent a high-risk surgical population for surgical site infections, characterized by complex procedures, potential intraoperative hemodynamic variations, and significant pharmacokinetic variability. Patients are managed in a perioperative setting including the operating room and postoperative admission to a surgical intensive care or intermediate care unit.
Cohort
Prospective
Not listed
PK/PD target attainment of piperacillin
Proportion of patients achieving the predefined\* PK/PD target during the perioperative period \*estimated free concentration of piperacillin (80% of the total concentration) above the MIC of the isolated pathogen from bile samples throughout the surgical procedure (from incision to wound closure)
Plasma piperacillin concentration
Total (measured) et free (estimated) concentration of piperacilline throughout at two timepoints: surgical incision and wound closure
Factors associated with target attainment
Analysis of clinical and biological covariates associated with pharmacokinetic variability and the achievement of pharmacodynamic targets
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