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Clinical Trial
. 2023 Sep 1;278(3):310-319.
doi: 10.1097/SLA.0000000000005955. Epub 2023 Jun 14.

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  1   2   3 , Brian C Brajcich  2 , Kimberly A Bertens  4 , Carlos H F Chan  5 , Carlos Fernandez-Del Castillo  6 , Paul J Karanicolas  7 , Shishir K Maithel  8 , Bradley N Reames  9 , Sharon M Weber  10 , Roberto J Vidri  10 , Henry A Pitt  11 , Vanessa M Thompson  2 , Mithat Gonen  1 , Susan K Seo  1 , Adam C Yopp  12 , Clifford Y Ko  2   13   14 , Michael I D'Angelica  1
Affiliations
Clinical Trial

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 et al. Ann Surg. .

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.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

Figure 1.
Figure 1.. Development of Patient Cohort
Patient flow through overall randomized clinical trial and identification of subset of patients with intraoperative biliary cultures for analysis.
Figure 2.
Figure 2.. Association between IOBC results, antibiotic administered, and development of surgical site infection
Vertical line represents no association between the listed organisms and SSI. The diamond is subgroup-specific odds ratio and whiskers represent 95% confidence interval. *Culture result uses sterile bile (no organisms) as reference group
Figure 3.
Figure 3.. Association between IOBC results, antibiotic administered, and development of clinically relevant postoperative pancreatic fistula
Vertical line represents no association between the listed organisms and CR-POPF. The diamond is subgroup-specific odds ratio and whiskers represent 95% confidence interval. *Culture result uses sterile bile (no organisms) as reference group
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References

    1. Schoeniger LO, Linehan DC. Wound Infections After Pancreaticoduodenectomy. JAMA Surg 2016;151:440. - PubMed
    1. Merkow RP, Bilimoria KY, Tomlinson JS, et al. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg 2014;260:372–7. - PubMed
    1. Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med 2018;379:2395–406. - PubMed
    1. Sandini M, Ruscic KJ, Ferrone CR, et al. Major Complications Independently Increase Long-Term Mortality After Pancreatoduodenectomy for Cancer. J Gastrointest Surg 2019;23:1984–90. - PubMed
    1. Beane JD, Borrebach JD, Zureikat AH, Kilbane EM, Thompson VM, Pitt HA. Optimal Pancreatic Surgery: Are We Making Progress in North America? Ann Surg 2021;274:e355–e63. - PubMed

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