Prophylactic antibiotics for pancreaticoduodenectomy: study protocol for a multicenter randomized controlled trial comparing tazobactam/piperacillin versus ampicillin/sulbactam

Pancreaticoduodenectomy (PD) is associated with a high incidence of surgical site infection (SSI), reported in 20-40% of cases. In patients undergoing preoperative biliary drainage (PBD), the risk is further increased due to biliary contamination. Tazobactam/piperacillin (TAZ/PIPC) has been shown to reduce SSI compared with cephalosporins; however, no prospective trial has directly compared TAZ/PIPC with ampicillin/sulbactam (ABPC/SBT), which is widely used in pancreatic surgery. This study aims to evaluate the superiority of TAZ/PIPC over ABPC/SBT in preventing SSI after PD.

This is a multicenter, open-label, randomized controlled trial. A total of 320 patients undergoing PD will be randomized (1:1) to receive either TAZ/PIPC or ABPC/SBT as perioperative prophylactic antibiotics. Randomization will be stratified by PBD, minimally invasive surgery (MIS), and pancreatic ductal adenocarcinoma (PDAC). Antibiotics will be administered within 60 min before incision, redosed intraoperatively every 2-4 h, and continued every 8 h until postoperative day 1. The primary endpoint is the incidence of SSI within 30 days postoperatively, defined according to CDC criteria. Secondary endpoints include postoperative complications (Clavien-Dindo ≥IIIa), clinically relevant postoperative pancreatic fistula (ISGPS grade B/C), delayed gastric emptying, postpancreatectomy hemorrhage, bile leakage, mortality, reoperation, readmission, C. difficile colitis, and detection of antimicrobial-resistant organisms.

This trial will provide the first direct comparison between TAZ/PIPC and ABPC/SBT in PD. The results are expected to contribute to optimizing perioperative antibiotic strategies while balancing SSI prevention and antimicrobial resistance.

Japan Registry of Clinical Trials (jRCT), jRCTs051260063.