美国纪念斯隆凯特琳癌症中心Michael I. D’Angelica团队比较了哌拉西林-他唑巴坦与头孢西丁预防胰十二指肠切除术后感染的疗效。2023年4月20日出版的《美国医学会杂志》发表了这项成果。

尽管围手术期死亡率有所改善，但胰十二指肠切除术后手术部位感染（SSI）的发生率仍然很高。广谱抗菌外科预防在降低SSI方面的作用尚不清楚。为了与标准护理抗生素相比，确定广谱围手术期抗菌预防对术后SSI发生率的影响，研究组在美国和加拿大的26家医院进行了一项务实、开放标签、多中心、随机3期临床试验。参与者于2017年11月至2021年8月注册，随访至2021年12月。

研究组招募接受开放式胰十二指肠切除术的成人，无论有任何适应症，都符合条件。如果个体对研究药物过敏、活动性感染、慢性类固醇使用、严重肾功能障碍或怀孕或哺乳，则将其排除在外。参与者以1:1的比例进行随机分组，并根据术前胆道支架的存在进行分层。分析试验数据的参与者、研究人员和统计学家不受治疗分配的影响。

干预组接受哌拉西林-他唑巴坦（3.375g或4g静脉注射）作为围手术期抗菌预防，而对照组接受头孢西丁（2g静脉注射；标准护理）。主要结局是术后30天内出现SSI。次要终点包括30天死亡率、临床相关术后胰瘘的发展和败血症。所有数据都是作为美国外科学院国家外科质量改进计划的一部分来收集。

根据预先确定的停止规则，在临时分析时终止了试验。778名参与者中，哌拉西林-他唑巴坦组378人的中位年龄为66.8岁，男性233人（61.6%）；头孢西丁组400人的中位年龄68.0岁，男性223人（55.8%）。哌拉西林-他唑巴坦组围术期SSI百分比低于头孢西丁（19.8%对32.8%；绝对差异为−13.0%）。

与头孢西丁相比，接受哌拉西林-他唑巴坦治疗的参与者术后败血症（4.2%与7.5%；差异为−3.3%）和临床相关的术后胰瘘（12.7%与19.0%）发生率较低。接受哌拉西林-他唑巴坦治疗的参与者在30天时的死亡率为1.3%（5/378），接受头孢西丁治疗的参与者30天死亡率为2.5%（10/400）（差异为-1.2%）。

研究结果表明，在接受开放性胰十二指肠切除术的参与者中，使用哌拉西林-他唑巴坦作为围手术期预防，可减少术后SSI、胰瘘和SSI的多种后遗症。研究结果支持使用哌拉西林-他唑巴坦作为开放性胰十二指肠切除术的标准护理。

附：英文原文

Title: Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial

Author: Michael I. D’Angelica, Ryan J. Ellis, Jason B. Liu, Brian C. Brajcich, Mithat Gnen, Vanessa M. Thompson, Mark E. Cohen, Susan K. Seo, Emily C. Zabor, Michele L. Babicky, David J. Bentrem, Stephen W. Behrman, Kimberly A. Bertens, Scott A. Celinski, Carlos H. F. Chan, Mary Dillhoff, Matthew E. B. Dixon, Carlos Fernandez-del Castillo, Sepideh Gholami, Michael G. House, Paul J. Karanicolas, Harish Lavu, Shishir K. Maithel, John C. McAuliffe, Mark J. Ott, Bradley N. Reames, Dominic E. Sanford, Umut Sarpel, Courtney L. Scaife, Pablo E. Serrano, Travis Smith, Rebecca A. Snyder, Mark S. Talamonti, Sharon M. Weber, Adam C. Yopp, Henry A. Pitt, Clifford Y. Ko

Issue&Volume: 2023-04-20

Abstract:

Importance  Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood.

Objective  To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics.

Design, Setting, and Participants  Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment.

Intervention  The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care).

Main Outcomes and Measures  The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program.

Results  The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, 13.0% [95% CI, 19.1% to 6.9%]; P<.001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, 3.3% [95% CI, 6.6% to 0.0%]; P=.02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, 6.3% [95% CI, 11.4% to 1.2%]; P=.03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, 1.2% [95% CI, 3.1% to 0.7%]; P=.32).

Conclusions and Relevance  In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy.

DOI: 10.1001/jama.2023.5728

Source: https://jamanetwork.com/journals/jama/fullarticle/2804245