Broad-spectrum antibiotic prophylaxis ok for reducing surgical site infection after pancreatic surgery

The study of 778 patients undergoing open pancreatoduodenectomy revealed that piperacillin-tazobactam as perioperative prophylaxis lowered postoperative surgical-site infections (SSIs), pancreatic fistula and several downstream sequelae of SSI.

There is no proper understanding of the effect of broad-spectrum antimicrobial surgical prophylaxis in reducing surgical site infections. Therefore, Michael I. D'Angelica, Memorial Sloan Kettering Cancer Center, New York, New York, and colleagues aimed to define the effect of broad-spectrum perioperative antimicrobial prophylaxis (prevention) on postoperative incidence of SSI compared with standard care antibiotics in a pragmatic, open-label, multicenter, randomized phase 3 clinical trial. The authors noted that postoperative SSI incidence remains high after pancreatoduodenectomy despite improvements in perioperative mortality.

They addressed whether perioperative broad-spectrum antibiotics reduce postoperative surgical site infection after open pancreatoduodenectomy.

The trial, conducted at 26 hospitals across the US and Canada, included adult patients undergoing open pancreatoduodenectomy for any indication. Those with allergies to study medications, chronic steroid use, significant kidney dysfunction, active infections, and pregnancy were excluded.

778 Participants were block randomized in a ratio of 1:1 to receive intravenous piperacillin-tazobactam as perioperative antimicrobial prophylaxis (intervention group; n=378, 66.8 years; 61.6% men) or standard care cefoxitin (control group; n=400, median age, 68.0 years, 55.8% men).

The study's primary outcome was the development of postoperative SSI within 30 days. Secondary endpoints were sepsis, 30-day mortality, and clinically relevant postoperative pancreatic fistula development.

The authors reported the following findings:

• The trial was stopped at an interim analysis based on a predefined stopping rule.
• Of 778 participants, the SSI percentage at 30 days was lower in the perioperative piperacillin-tazobactam versus the cefoxitin group (19.8% vs 32.8%).
• Participants treated with piperacillin-tazobactam versus cefoxitin had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, −3.3%) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, −6.3%).
• Mortality rates at 30 days were 1.3% among participants treated with piperacillin-tazobactam and 2.5% among those receiving cefoxitin.

Perioperative use of piperacillin-tazobactam as antimicrobial prophylaxis reduced the risk of postoperative surgical site infection compared with standard care in patients undergoing pancreatoduodenectomy.

The authors observed that the reduction was seen irrespective of the presence of preoperative biliary stent and supported piperacillin-tazobactam as standard care for open pancreatoduodenectomy.

Reference:

D’Angelica MI, Ellis RJ, Liu JB, et al. Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial. JAMA. Published online April 20, 2023. doi:10.1001/jama.2023.5728