Should Preoperative Biliary Decontamination Be Considered to Minimize Morbidity and Mortality Following Pancreatoduodenectomy?

Background: Pancreatoduodenectomy (PD) remains the fundamental treatment for periampullary malignancies but is associated with considerable morbidity (20–50%) and mortality (2–7%). Bacteriobilia contributes to unfavourable postoperative outcomes. Current antibiotic prophylaxis recommendations endorse first-generation cephalosporins, which often fail to adequately target pathogens most frequently isolated from bile. To date, no specific guidelines for preoperative targeted antibiotic therapy have been established, although tailoring such strategies to the bile microbiome may improve surgical outcomes. This study aimed to characterize bile microbiology in patients undergoing PD for pancreatic ductal adenocarcinoma (PDAC), evaluating potential antibiotherapy regimens that provide effective coverage against the most frequently isolated pathogens. Methods: A retrospective cohort analysis of 725 patients surgically treated for pancreatic tumours at a high-volume pancreatic surgery center between 2017 and 2022 was performed. To minimize heterogeneity, study was restricted to 138 patients who underwent PD with histopathological confirmed PDAC. Intraoperative bile cultures were assessed. Results: Patients with bacteriobilia likewise experienced worse outcomes: higher 5-year mortality (OR 3.01, p = 0.007), greater overall postoperative pancreatic fistula (POPF) occurrence (OR 2.54, p = 0.044) and wound infections (OR 2.90, p = 0.038). Among bile microbiome the highest susceptibility rates were observed for combination of amoxicillin/clavulanic acid with gentamicin, while the lowest were noted for cephalosporin–metronidazole regimen (93.6% vs. 30.2%, respectively). Conclusions: Bacteriobilia contributes to postoperative complications and serves as a predictor of poorer survival after PD. Standard perioperative antibiotic prophylaxis in PD is insufficient. Based on our findings, perioperative antibiotic therapy with amoxicillin/clavulanic acid and gentamicin combination appears to provide superior coverage and may improve postoperative morbidity and overall survival following PD.