Targeting the Patient Microbiome for the Prevention of Surgical Site Infection in Spine Surgery

项目总结/摘要 手术部位感染（SSI）是一个主要的公共卫生问题，具有毁灭性的围手术期结局， 影响多达1/20的接受脊柱内固定手术的患者。脊柱融合术等手术 包括美国外科护理支出的最大类别，并且经常用于 患有各种肌肉骨骼疾病引起的疼痛或残疾的患者，例如先天性或 退行性疾病、创伤和肿瘤性疾病。然而，脊柱内固定手术的SSI发生率 在涉及干净皮肤切口的任何手术中， 几十年来。在脊柱手术中开发更有效的SSI预防策略具有重要意义 由于缺乏对致病细菌起源的基本了解， 脊柱伤口感染，背部微生物组，以及抗菌素耐药性对手术的作用 预防。我们最近证实，脊柱SSI的微生物原因可能因手术节段而异 和患者性别，并且大多数感染对给予的外科抗生素预防具有抗性。 本K23提案的目标是通过翻译培训在此基础上建立 微生物组科学，并通过前瞻性地表征患者微生物组在脊柱SSI中的作用。的 中心假设是大多数脊柱SSI是由手术前患者体内的应变引起的（而不是 而不是在医院环境中获得）以及术前患者的临床上可操作的特征 微生物组强烈影响个体，可改变的风险。这项工作的长期目标是使用新的 细菌基因组技术和大型临床数据集，以确定基本机制， 脊柱伤口感染的发生，使更有效的预防策略的发展。具体 本建议的目的是：1）确定术前金黄色葡萄球菌的细菌遗传特征 与脊柱SSI相关，允许开发改进的筛查和去殖民化措施，2） 确定内源性革兰氏阴性脊柱SSI来源和相关的外科抗生素耐药性 预防，使预防战略，这一重要类别的感染， 影响特定群体（例如，接受腰骶手术的女性），以及3）确定临床风险因素 针对脊柱手术中对外科抗生素预防的耐药性， 不同患者人群脊柱手术中的抗生素预防。 这些研究活动与我的职业发展计划密切相关。通过团队， 来自麻醉学、外科学和分子微生物学的专家导师，我将接受以下培训： 尖端的翻译微生物组研究和职业发展走向独立。这个奖项将 准备我的第一份R01提交文件，内容是脊柱临床使用的定制SSI预防工具/策略 外科手术和围手术期感染预防的独立转化研究事业。

PROJECT SUMMARY/ABSTRACT Surgical site infection (SSI) is a major public health problem with devastating perioperative outcomes, affecting as many as 1 in 20 patients undergoing instrumented spine surgery. Procedures such as spinal fusion comprise the largest overall category of US spending on surgical care and are frequently performed for patients with pain or disability arising from a wide range of musculoskeletal conditions, such as congenital or degenerative disease, trauma, and neoplastic disorders. However, SSI rates in instrumented spine surgery are among the highest of any procedure involving a clean skin incision and they have not substantially decreased in decades. The development of more effective strategies for SSI prevention in spine surgery is significantly limited by a lack of fundamental understanding about the origins of causative bacteria, the basic pathogenesis of spinal wound infection, the microbiome of the back, and the role of antimicrobial resistance to surgical prophylaxis. We recently demonstrated that the microbiologic causes of spine SSI may vary by operative level and patient sex, and that most infections are resistant to the surgical antibiotic prophylaxis administered. The objectives of this K23 proposal are to build upon this foundation through training in translational microbiome sciences and by prospectively characterizing the role of the patient microbiome in spine SSI. The central hypothesis is that most spine SSIs arise from strains colonizing the patient prior to surgery (rather than acquired in the hospital environment) and that clinically actionable features of the preoperative patient microbiome strongly influence individual, modifiable risk. The long-term objective of this work is to use novel bacterial genomic techniques and large clinical datasets to identify the fundamental mechanisms by which spinal wound infection occurs, enabling the development of more effective prevention strategies. The specific aims of this proposal are to: 1) define preoperative bacterial genetic features of Staphylococcus aureus associated with spine SSI, allowing development of improved screening and decolonization measures, 2) identify sources of endogenous gram-negative spine SSI and associated resistance to surgical antibiotic prophylaxis, enabling prevention strategies for this important class of infection that may disproportionately affect specific groups (e.g., women undergoing lumbosacral procedures), and 3) determine clinical risk factors for resistance to surgical antibiotic prophylaxis in spine surgery to inform tailored approaches to selection of antibiotic prophylaxis in spine surgery for diverse patient populations. These research activities are closely aligned with my career development plans. Through the team of expert mentors assembled from anesthesiology, surgery, and molecular microbiology, I will receive training in cutting-edge translational microbiome research and career development toward independence. This award will prepare me for my first R01 submission on tailored SSI prevention tools/strategies for clinical use in spine surgery and for an independent translational research career in perioperative infection prevention.