Intraoperative Bile Coverage by Ampicillin–Sulbactam and Simulated Piperacillin–Tazobactam in Pancreato-Duodenectomy: A Retrospective Single-Centre Study

Background/Objectives: Clinical trials have shown that piperacillin–tazobactam prophylaxis is beneficial in pancreatoduodenectomy, especially after preoperative biliary drainage, yet patient-level microbiological data are scarce. We compared the observed coverage of intraoperative bile isolates by our institutional standard for stented patients, ampicillin–sulbactam, with the coverage that the guideline-endorsed piperacillin–tazobactam would have provided, as estimated by simulation. Methods: Retrospective study of consecutive elective PD patients from 2015 to 2023. Microbiological complete coverage denoted susceptibility of all bile isolates. For stented patients receiving ampicillin–sulbactam, we simulated piperacillin–tazobactam susceptibility sequentially until complete coverage was achieved. Non-stented patients were studied separately. Pathogen persistence, postoperative outcome parameters and antibiotic escalation were evaluated. Results: Of 363 patients, 177 underwent preoperative biliary stenting, of whom 160 received ampicillin–sulbactam. Coverage was complete in 63 (39.4%), incomplete coverage in 97 (60.6%). Among the latter, simulated piperacillin–tazobactam coverage was complete in 65 (67.0%). Assuming a translation of initial ampicillin–sulbactam coverage to piperacillin–tazobactam, an upper limit for coverage of 128/160 (80.0%) was reached. In exploratory clinical outcome analyses, incomplete ampicillin–sulbactam coverage was associated with more abdominal wound infections (25.8% versus 11.1%, p = 0.027). CR-POPF (17.5% vs. 13.4%, p = 0.325) or the rate of intra-abdominal abscesses (20.6% vs. 16.5%, p = 0.534) were not statistically different. With simulated piperacillin–tazobactam coverage wound infection rates did not any more differ significantly (23.1% vs. 31.3%, p = 0.461). CR-POPF and intraabdominal abscesses remained statistically indifferent. Ampicillin–sulbactam was escalated for infectious complications in 44/97 patients (45.4%), mainly to piperacillin–tazobactam or ciprofloxacin. Conclusions: Simulated piperacillin–tazobactam offered broader microbiological coverage than ampicillin–sulbactam. Although this benefit was limited to wound infections, these patient-level findings support both our long-standing practice of escalated prophylaxis in stented patients and adherence to the updated guideline recommendations.