Background/Objectives: A positive intraoperative bile culture (bacterobilia) is considered to be a risk factor for increased morbidity after pancreatoduodenectomy. The aim of our study was to describe the frequency of bacterobilia with a special emphasis on antibiotic resistance and to analyze the association of these findings with postoperative complications, in particular with postoperative pancreatic fistula. Methods: From a prospective database, patients with available intraoperative bile cultures (n = 95) were selected and analyzed. Microbiological test results reported the type of bacteria as well as sensitivity and resistance patterns. Associations between culture results, antibiotic resistance, and postoperative outcomes were assessed. Results: Among 95 patients that were included in this trial, 71 (74.7%) had a positive bile culture. A total of 29.6% (21/71) of patients with positive bile cultures developed POPF grade B/C compared to 8.3% (2/24) of patients with negative bile cultures (p = 0.052). The difference in CR-POPF became statistically significant when at least one of the isolated microorganisms was resistant to ampicillin/sulbactam, the perioperative antibiotic administered for prophylaxis. CR-POPF was diagnosed in 38.5% (15/39) of patients with antibiotic resistance vs. 14.3% (8/56) of patients without resistant microorganisms (p = 0.007). We also identified the isolation of Enterococcus spp. (p = 0.006), resistant Enterobacter (p = 0.031), or resistant Escherichia coli (p = 0.027) as risk factors for pancreatic fistula. Conclusions: The isolation of antibiotic-resistant strains in a positive bile culture is a major risk factor for the development of pancreatic fistula after pancreatoduodenectomy. The most relevant bacteria in our study were Enterococcus spp., Enterobacter cloacae, and Escherichia coli. Thus, broad-spectrum antimicrobial prophylaxis with efficacy against these microorganisms and with low resistance rates should be routinely administered perioperatively.
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