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Your next patient is scheduled for a pancreatoduodenectomy. You are concerned about the risk of surgical site infection and are considering options for perioperative antibiotic prophylaxis. According to a recent study comparing a cephalosporin (cefoxitin) against a broad-spectrum antimicrobial combination (piperacillin-tazobactam), which of the following is the MOST likely outcome with the administration of piperacillin-tazobactam?
(A) Longer hospital stay X
(B) Higher rate of mortality X
(C) Lower rate of surgical site infection ✔
Gain insight on this topic, and many others, with Summaries of Emerging Evidence (SEE) 2025 – Volume 41A now available. The content is aggregated from 30 international medical journals to streamline your learning and improve your practice.
Pancreatoduodenectomy is associated with significant postoperative morbidity, such as pancreatic fistula and surgical site infection (SSI). Several factors contribute to the high rate of SSI: postoperative anastomotic leak, pancreatic fistulas, preoperative biliary instrumentation (bile inoculation with bacteria), and intraoperative intra-abdominal bile contamination. Current guidelines recommend first or second generation cephalosporins for perioperative prophylaxis, but they provide limited coverage of resistant organisms that are thought to contribute significantly to postoperative SSI after these surgical procedures.
A recent pragmatic randomized controlled trial was conducted using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data registry to evaluate the effectiveness of broad-spectrum coverage (piperacillin-tazobactam) versus cefoxitin for the prevention of postoperative SSI following pancreatoduodenectomy. This open-label trial of adults was conducted from 2017 to 2021 at 26 centers in the United States and Canada. The initial enrollment was 967 patients who were equally randomized to the 2 antibiotic regimens. The trial was terminated early with 778 evaluable patients (n = 378 patients in the piperacillin-tazobactam group, n = 400 patients in the cefoxitin group), due to attainment of the efficacy threshold. Patients received either cefoxitin (2 g intravenously) or piperacillin-tazobactam (3.375 g or 4.5 g intravenously) within 60 minutes of incision, and additional doses of the antibiotics were administered every 2 to 4 hours until the end of surgery. Antibiotics were not to be given beyond 24 hours after incision closure. The primary outcome was the development of any SSI within 30 days of the procedure.
The primary outcome occurred in 19.8% (75 of 378) of patients in the piperacillin-tazobactam group versus 32.8% (131 of 400) in the cefoxitin group. The absolute risk difference was –13% (95% CI, –19.1% to –6.9%). Lower rates of superficial SSI and organ space SSI were also found in the piperacillin-tazobactam group. No difference was found between groups in any of the numerous secondary outcomes. Notably, patients in the piperacillin-tazobactam group had lower rates of pancreatic fistula formation. The median hospital length of stay was 7 days for both groups and the 30-day mortality rate was low in both groups (1.3% in the piperacillin-tazobactam group vs 2.5% in the cefoxitin group).
In summary, a recent multicenter, pragmatic randomized trial that compared cefoxitin with piperacillin-tazobactam for the prevention of SSI in patients undergoing pancreatoduodenectomy found that patients who received piperacillin-tazobactam perioperatively had a lower rate of postoperative SSI. The study authors concluded that piperacillin-tazobactam prophylaxis should become the standard of care for patients undergoing this surgery.
Reference
Date of last update: January 15, 2025
