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

基本信息

批准号：
10348358
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
项目类别：
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/10348358
关键词：
Affect Age Anatomy Anesthesiology Anterior Antibiotic Prophylaxis Antibiotic Therapy Antimicrobial Resistance Award Back Bacteria Bacterial Genome Caring Categories Cefazolin Cervical Cessation of life Chest Clinical Complex Data Set Degenerative Disorder Development Development Plans Disease Eligibility Determination Environment Escherichia Foundations Future Genetic Genetic Determinism Genomics Goals Hospitals Individual Infection Infection prevention Klebsiella Lead 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 Public Health 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 host colonization 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

项目摘要

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.

项目概要/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结果，影响多达二十分之一接受脊柱器械手术的患者。脊柱融合等手术构成美国外科护理支出中最大的一类，并且经常用于以下目的：因各种肌肉骨骼疾病（例如先天性或先天性疾病）引起的疼痛或残疾的患者退行性疾病、创伤和肿瘤性疾病。然而，脊柱器械手术中的 SSI 率是所有涉及清洁皮肤切口的手术中最高的，而且它们并没有大幅减少几十年来。制定更有效的脊柱手术 SSI 预防策略具有重要意义由于缺乏对致病菌起源、基本发病机制的基本了解而受到限制脊柱伤口感染、背部微生物组以及手术抗菌药物耐药性的作用预防。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，并且大多数感染对外科抗生素预防治疗具有耐药性。 K23 提案的目标是通过转化培训在此基础上发展微生物组科学，并前瞻性地描述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 是由手术前定植于患者的菌株引起的（而不是比在医院环境中获得的）以及术前患者的临床可操作特征微生物组强烈影响个体的、可改变的风险。这项工作的长期目标是使用新颖的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，使得能够制定更有效的预防策略。具体的该提案的目的是：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，允许开发改进的筛查和去殖民化措施，2) 确定内源性革兰氏阴性脊柱 SSI 的来源以及对手术抗生素的相关耐药性预防，为这一类重要的感染制定预防策略，这种感染可能不成比例影响特定群体（例如接受腰骶手术的女性），以及 3) 确定临床风险因素脊柱手术中对手术抗生素预防的耐药性，为选择合适的方法提供信息针对不同患者群体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密切相关。通过团队由麻醉学、外科、分子微生物学专家组成的导师，我将接受以下方面的培训：尖端的转化微生物组研究和职业发展走向独立。该奖项将为我的第一份 R01 提交做好准备，提交有关脊柱临床使用的定制 SSI 预防工具/策略手术以及围手术期感染预防方面的独立转化研究生涯。