A New Gold Standard? Impact of Broad-spectrum Penicillin-based Antibiotic Prophylaxis on Outcome After Pancreatoduodenectomy: Results of a Systematic Review and Meta-analysis (PROSPERO CRD42024559197)

Objective: This review evaluated whether broad-spectrum penicillin-based antibiotic prophylaxis (BS-AB) such as piperacillin-tazobactam might lead to better outcomes in pancreatoduodenectomy compared with standard care antibiotics, mainly cephalosporins (CE-AB). Background: Pancreatoduodenectomy is commonly associated with high postoperative infectious complications, contributing to increased morbidity, mortality, and health care costs. Methods: A systemic literature search (PubMed, EMBASE, Cochrane Library, and Web of Science) was conducted to identify suitable RCTs and non-RCTs. After inclusion, the data were analyzed using a random-effects model with the Mantel-Haenszel model or inverse variance to calculate odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI). Results: One RCT and 11 non-RCTs were included with 12,469 patients (35.3% BS-AB, 64.7% CE-AB). Surgical site infections (SSI) were significantly lower after BS-AB when compared with CE-AB, [OR 0.53; CI (0.32 to 0.86); P =0.01; I 2 =79%] as well as the occurrence of postoperative pancreatic fistula (POPF) [OR 0.62; CI (0.47 to 0.81); P <0.01; I 2 =0%], days of hospitalization [MD -2.02; CI (-4.08 to 0.03); P =0.05; I 2 =98%] and mortality [OR 0.56; CI (0.34 to 0.95); P =0.03; I 2 =0%]. Subgroup analyses of patients with preoperative biliary drainage demonstrated an even higher effect of BS-AB in reducing SSI [OR 0.45, CI (0.45 to 0.67); P =0.01; I 2 =78%], POPF [OR 0.52; CI (0.36 to 0.75); P <0.01; I 2 =0%] and mortality [OR 0.34; CI (0.15 to 0.76); P <0.01; I 2 =0%]. Conclusion: BS-AB significantly reduces the risk of infectious complications and surgical outcomes in pancreatoduodenectomy compared with CE-AB, particularly in patients with preoperative biliary drainage. These findings support the use of BS-AB as a new gold standard for patients undergoing pancreatoduodenectomy.