Background Pancreaticoduodenectomy (PD) is associated with high postoperative morbidity, particularly infectious complications. In patients undergoing preoperative biliary drainage (PBD), bile contamination is common and may lead to a mismatch between standard cephalosporin-based prophylaxis and biliary pathogens. Methods We conducted a retrospective single-center cohort study including 65 patients undergoing PD between December 2021 and May 2025. Of these, 42/65 (64.6%) underwent PBD. Patients received perioperative antibiotic prophylaxis with cefazolin or piperacillin/tazobactam plus fluconazole, according to institutional protocols. Intraoperative bile cultures were obtained in 44/65 patients, yielding 39 positive cultures with multiple isolates. Infectious complications and major morbidity (Clavien-Dindo > IIIA) were assessed. Multivariable logistic regression was performed to identify predictors of infectious complications, with subgroup analysis in drained patients. Results Positive bile cultures were observed in 38/42 (90.5%) drained patients compared with 1/23 (4.3%) non-drained patients (p<0.001). A total of 39 positive bile cultures yielded multiple isolates, including Enterococcus spp. in 24/39 (61.5%) cultures and Candida spp. in 10/39 (25.6%) cultures. Cefazolin did not provide coverage for at least one isolate in 30/39 (76.9%) cultures, compared with 13/39 (33.3%) for piperacillin/tazobactam plus fluconazole. In multivariable analysis restricted to drained patients, piperacillin/tazobactam plus fluconazole was independently associated with fewer infectious complications (odds ratio (OR): 0.13; 95% confidence interval (CI): 0.02-0.92; p=0.041). Conclusions In patients undergoing PD after PBD, bile contamination is frequent and characterized by enteric organisms and a relevant fungal component. Under these conditions, cefazolin prophylaxis shows a high rate of expected non-coverage, whereas piperacillin/tazobactam plus fluconazole provides broader microbiological coverage and is associated with reduced infectious complications. These findings support a tailored prophylactic strategy based on biliary colonization in PBD patients.
Ottaviani et al. (Wed,) studied this question.