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

针对患者微生物群预防脊柱手术中的手术部位感染

• 批准号: 10592249
• 负责人: Dustin R Long
• 金额: $ 16.63万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592249
• 关键词: Affect; Age; Anatomy; Anesthesiology; Anterior; Antibiotic Prophylaxis; Antibiotic Therapy; Antimicrobial Resistance; Award; Back; Bacteria; Bacterial Genome; Biological; Caring; Categories; Cefazolin; Cervical; Cessation of life; Chest; Clinical; Clinical Data; Complex; Data Set; Degenerative Disorder; Development; Development Plans; Disease; Environment; Escherichia; Foundations; Future; Genetic; Genetic Determinism; Genomics; Goals; Hospitals; Individual; Infection; Infection prevention; Klebsiella; Measures; Medical center; Mentors; Methicillin Resistance; Methods; Microbiology; Molecular; Molecular Epidemiology; Musculoskeletal; Nose; Operative Surgical Procedures; Outcome; Pain; Pathogenesis; Patients; Perioperative; Perioperative Care; Powder dose form; Prevention; Prevention Measures; Prevention strategy; Procedures; Prophylactic treatment; Proteus; Protocols documentation; Public Health; Registries; Repeat Surgery; Research; Research Activity; Resistance; Resistance to infection; Risk; Risk Factors; Role; Safety; Sampling; Skin; Source; Specimen; Spinal; Spinal Fusion; Spine surgery; Staphylococcus aureus; Surgical Wound Infection; Surgical incisions; Techniques; Training; Translational Research; Trauma; Vancomycin; Vertebral column; Woman; Work; Wound Infection; bacterial genetics; biomedical referral center; career; career development; clinical risk; clinically actionable; commensal bacteria; cost; disability; fecal microbiome; functional outcomes; genome wide association study; high risk; hospital readmission; improved; infection rate; instrument; instrumentation; men; methicillin resistant Staphylococcus aureus; microbiome; microbiome research; modifiable risk; molecular marker; nasal microbiome; neoplastic; novel; pathogen; patient population; personalized approach; preservation; prospective; research and development; screening; sex; skin microbiome; surgical risk; tool; trait; wound

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.

项目摘要/摘要 手术部位感染（SSI）是毁灭性围手术期结果的主要公共卫生问题， 在接受仪器脊柱手术的20例患者中有多达1个。脊柱融合等过程 构成了美国在外科护理上支出的最大总体类别，并且经常进行 由多种肌肉骨骼疾病（例如先天或先天性或 退化性疾病，创伤和肿瘤疾病。但是，仪器脊柱手术中的SSI率是 在任何涉及干净皮肤切口的手术中，最高 几十年来。在脊柱手术中为SSI预防的更有效策略的制定显着 由于缺乏对因果细菌的起源的基本理解的限制，基本的发病机理 脊柱伤口感染，背部的微生物组和抗菌素对手术的作用 预防。我们最近证明，脊柱SSI的微生物原因可能因手术水平而异 和患者性别，并且大多数感染对施用的手术抗生素预防具有抵抗力。 该K23提案的目标是通过翻译的培训以这一基础为基础 微生物组科学并通过前瞻性表征患者微生物组在脊柱SSI中的作用。这 中心假设是，大多数脊柱SSI是由在手术前定位患者的菌株（而是） 比在医院环境中获得的）和术前患者的临床功能 微生物组强烈影响个人，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，以确定基本机制 脊柱伤口感染发生，从而发展更有效的预防策略。具体 该建议的目的是：1）定义金黄色葡萄球菌的术前细菌遗传特征 与脊柱SSI相关，允许开发改进的筛选和非殖民化度量，2） 鉴定内源性革兰氏阴性脊柱SSI的来源以及对手术抗生素的抗性 预防，为这种重要类型的感染提供预防策略，可能不成比例 影响特定的群体（例如，接受腰椎程序的妇女）和3）确定临床风险因素 在脊柱手术中耐药性预防手术抗生素，以告知量身定制的方法 多种患者人群的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紧密相符。通过团队 专家指导者由麻醉，手术和分子微生物学组装，我将接受培训 尖端的翻译微生物组研究和职业发展。这个奖项将 为我准备我的第一个R01提交，以量身定制的SSI预防工具/策略用于脊柱 手术和围手术期感染的独立翻译研究职业。