July 26, 2023
What Is the Proper Antibiotic Prophylaxis for a Pancreatoduodenectomy (Whipple Procedure)?By Aldon Li, MD, FIDSA
Medical and surgical society guidelines recommend the use of first or second generation cephalosporins prior to incision to decrease surgical site infection (SSI) risk in gastroduodenal procedures, where the most common pathogenic organisms are coliforms, staphylococci, streptococci, enterococci, and anaerobes. Administration of these antimicrobials was found to reduce postoperative infection rates from 2%-66% in patients without cephalosporin prophylaxis to 0%-22% in patients who received prophylaxis. However, a small study looking at biliary tract pathogenic bacteria in patients undergoing pancreatoduodenectomy (PD) found that 97% of recovered bile bacteria were resistant to cefazolin and 83% were resistant to cefoxitin.
A recent multicentered study in JAMA, involving hospitals in the U.S. and Canada that participate in the ACS-NSQIP Program, randomized adults undergoing elective open PD (excluding laparoscopic or robotic procedures) to receive either piperacillin-tazobactam or cefoxitin within 60 minutes of incision, with additional doses during the operation every 2-4 hours until close of incision.
The primary endpoint was the development of SSI (as defined by CDC) within 30 days of the surgical procedure. Secondary endpoints observed the development of postoperative complications within 30 days after surgery, including mortality and Clostridioides difficile infection (CDI).
Between November 2017 and August 2021, the authors randomized 778 patients; 378 received piperacillin-tazobactam and 400 cefoxitin. The trial was stopped early after interim analysis found the piperacillin-tazobactam group had an almost 50% decrease in the odds of contracting an SSI compared to the cefoxitin group (19% vs 32% respectively; P < .001). The piperacillin-tazobactam group had a lower point estimate for mortality (but was not statistically significant) and significantly lower odds of developing CDI.
Aside from the limitations in the ACS-NSQIP Program as already discussed thoroughly in the accompanying editorial, the current study provides good evidence to strongly consider deviation from current guidelines to use piperacillin-tazobactam in patients undergoing PD. Future studies should define the microbiological milieu driving the large differences between the groups in this study to improve antibiotic stewardship practices, as piperacillin-tazobactam and cefoxitin have similar antimicrobial coverage, with piperacillin-tazobactam offering broader spectrum of activity against Enterococcus, Pseudomonas, and other enterics like Enterobacter, Citrobacter, Aeromonas, and Bacteroides. The authors speculate the lower risk of CDI in the piperacillin-tazobactam group stems from the decreased use of additional antibiotics given lower postoperative infectious complications, but further analysis of CDI rates should be done 60-90 days after surgery, given that CDI risk is known to be higher 3 months after antibiotic exposure.
