Perioperative Pharmacokinetic/Pharmacodynamic Target Attainment of Piperacillin During Major Hepatic and Pancreatic Surgery

PROPHTAZ: Evaluation of Pharmacokinetic/Pharmacodynamic Target Attainment of Piperacillin During Major Hepatic and Pancreatic Surgery, a Prospective Observational Pharmacokinetic Study

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.

Inclusion Criteria:

• Adults > or = to 18 years old
• Scheduled for major hepatic or pancreatic surgery
• Receiving piperacillin/tazobactam as perioperative antibiotic prophylaxis according to guidelines

Exclusion Criteria:

• decline to participate
• Known allergy of beta-lactam