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

项目摘要/摘要 手术部位感染(SSI)是一个重大的公共卫生问题，具有毁灭性的围手术期后果， 在接受脊柱内固定手术的20名患者中，有1人受到影响。脊柱融合术等手术 构成了美国外科护理总支出最大的类别，经常为 因各种肌肉骨骼疾病引起的疼痛或残疾的患者，如先天性或 退行性疾病、创伤和肿瘤疾病。然而，脊柱内固定手术的SSI比率是 在所有涉及清洁皮肤伤口的手术中，这一比例最高，而且并没有显著下降 几十年来。脊柱外科中预防SSI的更有效策略的发展具有重要意义 受限于对致病细菌的来源缺乏基本的了解，基本的致病机理 脊椎创面感染、背部微生物群和抗菌素耐药性对手术的作用 预防措施。我们最近证实，脊柱SSI的微生物学原因可能因手术节段不同而不同。 和病人的性别，而且大多数感染对外科抗生素预防措施具有抗药性。 K23提案的目标是通过翻译培训在此基础上再接再厉 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。这个 中心假设是，大多数脊柱SSI是由手术前感染患者的菌株引起的(更确切地说 与在医院环境中获得的相比)，以及术前患者的临床可操作特征 微生物群强烈影响个体的、可改变的风险。这项工作的长期目标是使用小说 细菌基因组技术和大型临床数据集，以确定其基本机制 脊柱伤口感染的发生，使制定更有效的预防策略成为可能。具体的 本建议的目的是：1)明确金黄色葡萄球菌的术前细菌遗传特征 与脊椎SSI相关联，使改进的筛查和非殖民化措施得以制定，2) 确定内源性革兰氏阴性脊柱SSI的来源及与外科抗生素相关的耐药性 预防，为这一重要类别的感染提供预防战略，这种感染可能不成比例 影响特定群体(例如，接受腰椎手术的妇女)，以及3)确定临床风险因素 对于脊柱手术中外科抗生素预防的耐药性，以告知选择适合的方法 脊柱手术中针对不同患者群体的抗生素预防。 这些研究活动与我的职业发展计划密切相关。通过以下团队 来自麻醉学、外科和分子微生物学的专家导师将在以下方面接受培训 最新的翻译微生物组研究和职业发展走向独立。这一奖项将 为我的第一份R01提交的脊柱临床使用的SSI预防工具/策略做好准备 在手术和围术期感染预防方面的独立翻译研究生涯。

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.