Piperacillin-tazobactam versus cefoxitin as perioperative prophylaxis for pancreatoduodenectomy: real world evidence from the EPIC Cosmos database

HPB (Oxford). 2025 Nov 4:S1365-182X(25)01675-2. doi: 10.1016/j.hpb.2025.10.012. Online ahead of print.

ABSTRACT

BACKGROUND: Antimicrobial prophylaxis with piperacillin-tazobactam was recently demonstrated to reduce the incidence of surgical site infections (SSI) and pancreatic fistula following open pancreatoduodenectomy (PD) compared with cefoxitin. Larger scale, real-world data to confirm effectiveness of piperacillin-tazobactam are lacking.

METHODS: Patients undergoing open PD between 2016 and 2024 were identified in the EPIC Cosmos database. Exposure included perioperative administration of piperacillin-tazobactam versus cefoxitin as antimicrobial prophylaxis. Outcomes included development of SSI, pancreatic fistula, sepsis, multidrug-resistant (MDR) infections, and mortality (all 30-day outcomes).

RESULTS: Among 4039 patients who underwent open PD, 2496 (61.8 %) received perioperative cefoxitin, while 1543 (38.2 %) received piperacillin-tazobactam. Over time, piperacillin-tazobactam replaced cefoxitin as the predominant antimicrobial prophylaxis (p-trend <0.001). Patients who received piperacillin-tazobactam had a higher Charlson comorbidity index, more frequently had a history of diabetes, smoking and more frequently had preoperative biliary stent placed compared with individuals who received cefoxitin (all p < 0.05). Patients receiving piperacillin-tazobactam had a lower incidence of any SSI, superficial SSI, deep incisional/organ space SSI, pancreatic fistula and sepsis compared with cefoxitin (all p < 0.05). No difference was observed in 30-day MDR infections or mortality (p > 0.05).

CONCLUSIONS: The use of prophylactic piperacillin-tazobactam was associated with better perioperative outcomes compared with cefoxitin among patients undergoing open PD.

PMID:41260995 | DOI:10.1016/j.hpb.2025.10.012