Association between Biliary Pathogens, Surgical Site Infection, and Pancreatic Fistula: Results of a Randomized Trial of Perioperative Antibiotic Prophylaxis in Patients Undergoing Pancreatoduodenectomy

Ryan J. Ellis, Brian C. Brajcich, Kimberly A. Bertens, Carlos H.F. Chan, Carlos Fernandez Del Castillo, Paul J. Karanicolas, Shishir K. Maithel, Bradley N. Reames, Sharon M. Weber, Roberto J. Vidri, Henry A. Pitt, Vanessa M. Thompson, Mithat Gonen, Susan K. Seo, Adam C. Yopp, Clifford Y. Ko, Michael I. D'Angelica

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Objective: To establish the association between bactibilia and postoperative complications when stratified by perioperative antibiotic prophylaxis. Background: Patients undergoing pancreatoduodenectomy experience high rates of surgical site infection (SSI) and clinically relevant postoperative pancreatic fistula (CR-POPF). Contaminated bile is known to be associated with SSI, but the role of antibiotic prophylaxis in mitigation of infectious risks is ill-defined. Methods: Intraoperative bile cultures (IOBCs) were collected as an adjunct to a randomized phase 3 clinical trial comparing piperacillin-tazobactam with cefoxitin as perioperative prophylaxis in patients undergoing pancreatoduodenectomy. After compilation of IOBC data, associations between culture results, SSI, and CR-POPF were assessed using logistic regression stratified by the presence of a preoperative biliary stent. Results: Of 778 participants in the clinical trial, IOBC were available for 247 participants. Overall, 68 (27.5%) grew no organisms, 37 (15.0%) grew 1 organism, and 142 (57.5%) were polymicrobial. Organisms resistant to cefoxitin but not piperacillin-tazobactam were present in 95 patients (45.2%). The presence of cefoxitin-resistant organisms, 92.6% of which contained either Enterobacter spp. or Enterococcus spp., was associated with the development of SSI in participants treated with cefoxitin [53.5% vs 25.0%; odds ratio (OR)=3.44, 95% CI: 1.50-7.91; P=0.004] but not those treated with piperacillin-tazobactam (13.5% vs 27.0%; OR=0.42, 95% CI: 0.14-1.29; P=0.128). Similarly, cefoxitin-resistant organisms were associated with CR-POPF in participants treated with cefoxitin (24.1% vs 5.8%; OR=3.45, 95% CI: 1.22-9.74; P=0.017) but not those treated with piperacillin-tazobactam (5.4% vs 4.8%; OR=0.92, 95% CI: 0.30-2.80; P=0.888). Conclusions: Previously observed reductions in SSI and CR-POPF in patients that received piperacillin-tazobactam antibiotic prophylaxis are potentially mediated by biliary pathogens that are cefoxitin resistant, specifically Enterobacter spp. and Enterococcus spp.

Original languageEnglish (US)
Pages (from-to)310-319
Number of pages10
JournalAnnals of surgery
Volume278
Issue number3
DOIs
StatePublished - Sep 1 2023

Keywords

  • antibiotic prophylaxis
  • pancreatoduodenectomy
  • surgical infection

ASJC Scopus subject areas

  • Surgery

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