Introduction

The prevalence of severe perioperative morbidity resulting due to surgical site infections (SSIs) and postoperative pancreatic fistulas (POPFs) is significant following pancreatoduodenectomy (PD). The recommended antibiotics for surgical prophylaxis for the procedures involving the biliary tract are cefzolin, second-generation cephalosporins, third-generation cephalosporins of ampicillin/sulbactam. However, antibiotic resistance reduces the efficacy of traditional antibiotics. The common microorganisms in bile such as Enterococcus and Enterobacter exhibit resistance from 1^st generation to 3^rd generation antibiotics. Studies have demonstrated that administering broad-spectrum antibiotics such as piperacillin/tazobactam (PT) have been beneficial in reducing SSIs.

Aim

To compare the outcomes of antimicrobial prophylaxis with piperacillin/tazobactam vs traditional antibiotics during PD.

Method

Study Design

• Systematic review and meta-analysis

Treatment Strategy

• Comprehensive literature search was conducted using the databases of PubMed, Embase, Web of Science, CINAHL and clinical trial registries
• The study was registered in PROSPERO, the international prospective register of systematic reviews, and a systematic search of various databases was conducted
• The meta-analysis was structured using the patient/problem, intervention, comparison, outcome and study design (PICOS) framework
• The eligibility criteria for comparator studies required inclusion of a control cohort that received standard surgical prophylaxis, defined as a traditional antibiotic (TA) regimen
• This regimen consisted of administering one of the following antibiotics: cefoxitin, ceftriaxone, cefazolin, cefmetazole, or ampicillin/sulbactam

Endpoints

Primary Endpoint

• Incidence of SSIs

  Secondary Endpoints

• Complications
• Postoperative pancreatic fistulas
• Delayed gastric emptying (DGE)
• Sepsis
• Mortality

Results

• A total of eight studies involving 2382 patients who underwent PD were eligible
• Of these, 1196 patients received piperacillin/tazobactam and 1186 patients received traditional antibiotics (TA) as antibiotic prophylaxis during surgery
• The baseline characteristics of both groups were similar
• The incidence of SSIs was significantly lower in the PT group as compared to TA (OR 0.43; p<0.00001)
• Substantial reduction in the incidences of superficial SSIs (OR 0.34; p=0.02) and organ/space SSIs (OR 0.47; p=0.004) were noted in the PT group
• Comparison of primary and secondary endpoints is shown in Figure 1.

  Figure 1. Comparison of primary and secondary endpoints

• Prophylaxis with PT also resulted in lower rates of major surgical complications classified as Clavien-Dindo grade >III (OR 0.61; p=0.0008)
• The incidence of clinically relevant DGE grades 2-4 were similar in both groups; OR 1.09, p=0.55
• The PT group demonstrated lower rates of clinically relevant postoperative pancreatic fistulas (grades B and C), sepsis and mortality; (ORs 0.67, 0.36 and 0.51 respectively

Conclusion

• Surgical prophylaxis with piperacillin/tazobactam significantly reduced surgical‑site infections, major complications classified as Clavien-Dindo grade >III, clinically significant pancreatic fistulas, and mortality in patients undergoing pancreatoduodenectomy
• The findings provide strong support for using piperacillin/tazobactam as an effective surgical prophylaxis in current practice

 BJS Open. 2024 May 8;8(3): zrae066. Doi: 10.1093/bjsopen/zrae066.