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

Abstract

Objective: Establish the association between bactibilia and postoperative complications when stratified by perioperative antibiotic prophylaxis. Background: Patients undergoing pancreatoduodenectomy (PD) 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 (IOBC) were collected as an adjunct to a randomized phase 3 clinical trial comparing piperacillin-tazobactam with cefoxitin as perioperative prophylaxis in patients undergoing PD. After complication 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 one 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 or Enterococcus species, was associated with development of SSI in participants treated with cefoxitin (53.5% vs 25.0%; 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). Conclusion: 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.

Comparing cefazolin/metronidazole, piperacillin‐tazobactam, or cefoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study

“…10,24 In the substudy of the D'Angelica trial reported by Ellis et al, the presence of Enterococci species (n = 68, 29.4%) was associated with increased SSI in the CX group (OR: 2.33, 95% CI: 1.06−5.15) but not the PT group (OR: 0.55, 95% CI: 0.17−1.84), which may be explained by the coverage of enterococci by PT but not by CX. 25 However, prophylactic coverage for these species may not be as crucial for patients undergoing PD, depending on the institution. Current evidence demonstrates that the predominance of pathogens in SSI among PD patients may be a function of antibiotic selection for prophylaxis and therefore vary by institution.…”

Big data and RCT's in surgical oncology: Impact on improving hepatopancreatobiliary cancer surgical care on the global stage

“…The PANasta trial represents the most robust analysis comparing two different techniques of pancreato‐jejunal anastomosis and reported no difference between the Blumgart and Cattel‐Warren techniques 34 . Ellis et al have recently published the results of a robust RCT demonstrating a significant reduction in rates of CR‐POPF and surgical site infections by implementing piperacillin‐tazobactam in perioperative antibiotic prophylaxis for patients undergoing a PD 35 …”

Comment on the Recent Publication Entitled by Ellis et al. “Association Between Biliary Pathogens, Surgical Site Infection, and Pancreatic Fistula”

“…The article of Ellis et al 1 titled “Association Between Biliary Pathogens, Surgical Site Infection, and Pancreatic Fistula” 1 was read with considerable interest. This ancillary observational study included patients in whom an intraoperative bile culture (IOBC) was performed during the multicentric randomized controlled trial showing a reduction in postoperative surgical site infection (SSI) and clinically relevant postoperative pancreatic fistula in patients receiving piperacillin-tazobactam versus cefoxitin as prophylaxis for open pancreatoduodenectomy (PD).…”