Original Investigation April 24, 2019

Association of Duration and Type of Surgical Prophylaxis With Antimicrobial-Associated Adverse Events

Westyn Branch-Elliman, William O’Brien, Judith Strymish, et al

JAMA Surg. Published online April 24, 2019. doi:10.1001/jamasurg.2019.0569

Importance 背景

The benefits of antimicrobial prophylaxis are limited to the first 24 hours postoperatively. Little is known about the harms associated with continuing antimicrobial prophylaxis after skin closure.

抗生素预防的益处仅限于术后第一个24小时内。缝皮后继续抗生素预防所伴随的风险知之甚少。

Objective 目的

To characterize the association of type and duration of prophylaxis with surgical site infection (SSI), acute kidney injury (AKI), and Clostridium difficile infection.

研究预防种类及疗程与手术部位感染(SSI)、急性肾损伤(AKI)及难辨梭状芽孢杆菌感染的相关性。

Design, Setting, and Participants 试验设计、场景及研究人群

In this multicenter, national retrospective cohort study, all patients within the national Veterans Affairs health care system who underwent cardiac, orthopedic total joint replacement, colorectal, and vascular procedures and who received planned manual review by a trained nurse reviewer for type and duration of surgical prophylaxis and for SSI from October 1, 2008, to September 30, 2013, were included. Data were analyzed using multivariable logistic regression, with adjustments for covariates determined a priori to be associated with the outcomes of interest. Data were analyzed from December 2016 to December 2018.

这是一项多中心、全国回顾性队列研究，纳入患者为2008年10月1日至2013年9月30日间全国退伍军人医疗系统收治的患者，且接受心脏、全关节置换、结直肠及血管外科手术，并由经过培训的护士查阅手术预防种类、疗程及SSI发病情况。采用多因素logistic回归方法分析数据，并针对事先确定的与预后相关的协变量进行校正。

Exposures 暴露因素

Duration of postoperative antimicrobial prophylaxis (<24 hours, 24-<48 hours, 48-<72 hours, and ≥72 hours).

术后预防性抗生素持续时间（<24小时，24-48小时，48-72小时及≥72小时）

Main Outcomes and Measures 主要预后指标

Surgical site infection, AKI, and C difficile infection.

手术部位感染，AKI及难辨梭状芽孢杆菌感染

Results 结果

Of the 79 058 included patients, 76 109 (96.3%) were men, and the mean (SD) age was 64.8 (9.4) years. Among 79 058 surgical procedures in the cohort, all had SSI and C difficile outcome data available; 71 344 (90.2%) had AKI outcome data. After stratification by type of surgery and adjustment for age, sex, race, diabetes, smoking, American Society of Anesthesiologists score greater than 2, methicillin-resistant Staphylococcus aureus colonization, mupirocin, type of prophylaxis, and facility factors, SSI was not associated with duration of prophylaxis. Adjusted odds of AKI increased with each additional day of prophylaxis (cardiac procedure: 24-<48 hours: adjusted odds ratio [aOR], 1.03; 95% CI, 0.95-1.12; 48-<72 hours: aOR, 1.22; 95% CI, 1.08-1.39; ≥72 hours: aOR, 1.82; 95% CI, 1.54-2.16; noncardiac procedure: 24-<48 hours: aOR, 1.31; 95% CI, 1.21-1.42; 48-<72 hours: aOR, 1.72; 95% CI, 1.47-2.01; ≥72 hours: aOR, 1.79; 95% CI, 1.27-2.53). The risk of postoperative C difficile infection demonstrated a similar duration-dependent association (24-<48 hours: aOR 1.08; 95% CI, 0.89-1.31; 48-<72 hours: aOR, 2.43; 95% CI, 1.80-3.27; ≥72 hours: aOR, 3.65; 95% CI, 2.40-5.53). The unadjusted numbers needed to harm for AKI after 24 to less than 48 hours, 48 to less than 72 hours, and 72 hours or more of postoperative prophylaxis were 9, 6, and 4, respectively; and 2000, 90, and 50 for C difficile infection, respectively. Vancomycin receipt was also a significant risk factor for AKI (cardiac procedure: aOR, 1.17; 95% CI, 1.10-1.25; noncardiac procedure: aOR, 1.21; 95% CI, 1.13-1.30).

在入选的79 058名患者中， 76 109名 (96.3%)为男性，平均(SD)年龄为64.8 (9.4)岁。队列收录的总共79 058次手术操作都有SSI及难辨梭状芽孢杆菌感染的资料。；71 344次 (90.2%)有AKI的数据。根据手术种类进行分层，并对年龄、性别、种族、糖尿病、吸烟、ASA评分> 2分、MRSA定植、莫匹罗星、预防种类等因素进行校正后，SSI与预防时长并不相关。抗生素预防每延长1天，AKI的校正后比数增加（心脏手术：24-<48小时：校正后比数比[aOR], 1.03; 95% CI, 0.95-1.12; 48-<72小时: aOR, 1.22; 95% CI, 1.08-1.39; ≥72小时: aOR, 1.82; 95% CI, 1.54-2.16; 非心脏手术：24-<48小时: aOR, 1.31; 95% CI, 1.21-1.42; 48-<72小时: aOR, 1.72; 95% CI, 1.47-2.01; ≥72 小时: aOR, 1.79; 95% CI, 1.27-2.53）。术后难辨梭状芽孢杆菌感染的风险与抗生素预防时长也呈现类似的相关性（24-<48小时：aOR 1.08; 95% CI, 0.89-1.31; 48-<72小时: aOR, 2.43; 95% CI, 1.80-3.27; ≥72小时: aOR, 3.65; 95% CI, 2.40-5.53）。术后预防性抗生素使用24-<48小时、48-<72小时以及≥72小时，发生AKI需要伤害患者数分别为9, 6和4；发生难辨梭状芽孢杆菌感染则分别为2000、90及50。使用万古霉素是AKI的显著危险因素（心脏手术：aOR, 1.17; 95% CI, 1.10-1.25；非心脏手术：aOR, 1.21; 95% CI, 1.13-1.30）。

Conclusions and Relevance 结论与意义

Increasing duration of antimicrobial prophylaxis was associated with higher odds of AKI and C difficile infection in a duration-dependent fashion; extended duration did not lead to additional SSI reduction. These findings highlight the notion that every day matters and suggest that stewardship efforts to limit duration of prophylaxis have the potential to reduce adverse events without increasing SSI.

延长预防性抗生素时长伴随AKI及难辨梭状芽孢杆菌感染风险增加且呈时间依赖性；延长预防性抗生素使用不能减少SSI。这些发现表明使用抗生素的每一天都很关键，并提示限制预防性抗生素使用的措施可能减少不良事件，同时不增加SSI的风险。