Association Between Biliary Pathogens, Surgical Site Infection, and Pancreatic Fistula

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 eitherEnterobacterspp. orEnterococcusspp., 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, specificallyEnterobacterspp. andEnterococcusspp.