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Pancreaticoduodenectomy After Preoperative Biliary Drainage: A Single-Center Cohort Study of Piperacillin/Tazobactam

Luca Ottaviani¹, Giovanni Crotti², Andrea Celotti¹

¹General Surgery, ASST Cremona, Cremona, ITA.

|May 11, 2026

Insights

For pancreaticoduodenectomy (PD) patients with preoperative biliary drainage (PBD), bile contamination is common. Piperacillin/tazobactam plus fluconazole prophylaxis reduced infectious complications compared to cefazolin, suggesting tailored antibiotic strategies.

Area of Science:

Gastroenterology
Surgical Oncology
Infectious Diseases

Background:

Pancreaticoduodenectomy (PD) is linked to significant postoperative morbidity, especially infections.
Preoperative biliary drainage (PBD) in PD patients frequently leads to bile contamination.
Standard antibiotic prophylaxis may not cover common biliary pathogens in PBD patients.

Purpose of the Study:

To evaluate the effectiveness of different antibiotic prophylaxis regimens in PD patients who underwent PBD.
To identify predictors of infectious complications in PD patients, with a focus on those with PBD.
To assess the microbiological coverage of cefazolin versus piperacillin/tazobactam plus fluconazole against biliary pathogens.

Main Methods:

Retrospective single-center cohort study of 65 PD patients (December 2021 - May 2025).
42 patients underwent PBD; antibiotic prophylaxis included cefazolin or piperacillin/tazobactam plus fluconazole.
Intraoperative bile cultures analyzed; infectious complications and major morbidity assessed; multivariable logistic regression performed.

Main Results:

90.5% of drained patients had positive bile cultures, predominantly with Enterococcus and Candida species.
Cefazolin lacked coverage for at least one isolate in 76.9% of positive cultures.
Piperacillin/tazobactam plus fluconazole was associated with fewer infectious complications in drained patients (OR: 0.13; p=0.041).

Conclusions:

Bile contamination is frequent in PD patients post-PBD, featuring enteric and fungal organisms.
Cefazolin prophylaxis demonstrates inadequate coverage for common biliary isolates in this population.
Piperacillin/tazobactam plus fluconazole offers broader coverage and is linked to reduced infectious complications, supporting tailored prophylaxis.

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Abstract:

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.

Keywords:

antibiotic prophylaxis bile culture pancreaticoduodenectomy preoperative biliary drainage surgical infection

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