■尽管围手术期死亡率有所改善,胰十二指肠切除术后手术部位感染(SSI)的发生率仍然很高.广谱抗微生物手术预防在降低SSI中的作用知之甚少。
■定义广谱围手术期抗菌药物预防与标准治疗抗生素相比对术后SSI发生率的影响。
■务实,开放标签,多中心,在美国和加拿大的26家医院进行随机3期临床试验。参与者在2017年11月至2021年8月之间注册,随访至2021年12月。接受任何适应症的开放式胰十二指肠切除术的成年人都有资格。如果个人对研究药物过敏,他们将被排除在外,活动性感染,长期使用类固醇,严重的肾功能障碍,或怀孕或哺乳。参与者以1:1的比例进行分组随机分组,并根据术前胆道支架的存在进行分层。参与者,调查员,分析试验数据的统计学家对治疗分配不具有盲性.
■干预组接受哌拉西林-他唑巴坦(3.375或4g静脉注射)作为围手术期抗菌药物预防,而对照组接受头孢西丁(2g静脉注射;标准治疗)。
■主要结果是30天内发生术后SSI。次要终点包括30天死亡率,临床相关的术后胰瘘的发展,还有败血症.所有数据都是作为美国外科医生学会国家外科质量改进计划的一部分收集的。
■根据预定义的停止规则,在中期分析时终止试验。778名参与者(哌拉西林-他唑巴坦组378名[中位年龄,66.8岁;头孢西丁组男性233{61.6%}和400[中位年龄,68.0年;223{55.8%的男性]),围手术期哌拉西林-他唑巴坦与头孢西丁组相比,30天的SSI百分比较低(19.8%vs32.8%;绝对差异,-13.0%[95%CI,-19.1%至-6.9%];P<.001)。用哌拉西林他唑巴坦治疗的参与者,vs头孢西丁,术后脓毒症发生率较低(4.2%vs7.5%;差异,-3.3%[95%CI,-6.6%至0.0%];P=0.02)和临床相关的术后胰瘘(12.7%vs19.0%;差异,-6.3%[95%CI,-11.4%至-1.2%];P=0.03)。在接受哌拉西林他唑巴坦治疗的参与者中,30天时的死亡率为1.3%(5/378),接受头孢西丁治疗的参与者为2.5%(10/400)(差异,-1.2%[95%CI,-3.1%至0.7%];P=.32)。
■在接受开放式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降低术后SSI,胰瘘,和SSI的多个下游后遗症。研究结果支持使用哌拉西林-他唑巴坦作为开放式胰十二指肠切除术的标准治疗。
■ClinicalTrials.gov标识符:NCT03269994。
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.
To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics.
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.
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).
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.
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).
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.
ClinicalTrials.gov Identifier: NCT03269994.