Role of immune system in prophylaxis antibiotic's surgical site infection control

免疫系统在预防性抗生素控制手术部位感染中的作用

基本信息

批准号：
10115388
负责人：
SASHA H SHAFIKHANI
金额：
$ 39.25万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-23 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10115388
关键词：
Address Allergic Reaction Animal Model Animals Antibiotic Prophylaxis Antibiotic Resistance Antibiotic Therapy Antibiotics Bacterial Infections Bioavailable Biological Cessation of life Clostridium difficile Data Development Effectiveness Focal Infection Health Health Expenditures Health behavior Hospitalization Immune Immune System Diseases Immune response Immune system Immunocompetent Immunocompromised Host Immunomodulators Impairment Implant Infection Infection Control Inflammasome Inflammation Inflammatory Response Innate Immune Response Innate Immune System Knowledge Laboratories Leukocytes Link Long-Term Effects Mediating Methods Modeling Molecular Morbidity - disease rate Muscle Mycoses Neutropenia Ohio Operating Rooms Operative Surgical Procedures Oxygen Pattern Pattern recognition receptor Perioperative Phagocytes Physiological Processes Play Pseudomonas aeruginosa Public Health Risk Role Site Staphylococcus aureus Sterilization Surgical Wound Infection Systemic infection Techniques Testing Therapeutic Tissues United States Dept. of Health and Human Services Universities Virus Diseases antimicrobial bactericide base combat cost cytotoxicity diabetic diabetic rat dysbiosis effectiveness evaluation emerging antibiotic resistance glycemic control gut microbiota improved in vivo interest mortality nervous system disorder neutrophil novel novel strategies pathogen prophylactic side effect skills standard of care synergism tissue repair ventilation wound

项目摘要

Role of immune system in prophylaxis antibiotic’s surgical site infection control Despite many advances in infection control practices – including improved operating room ventilation, barriers, sterilization methods, improved surgical techniques, surgical site infection (SSI) remains a significant cause of morbidity, prolonged hospitalization, and death with an estimated annual cost of $3.5 to $10 billion in healthcare expenditures in the US alone. Administration of prophylaxis antibiotics in the perioperative period (~1h prior to surgery) is the standard of care for most surgical procedures. However, even short-term antibiotic use is associated with the emergence of antibiotic resistance, as well as, increased risk for Clostridium difficile infection, and immunological and neurological diseases, many of which have been attributed to dysbiosis in the gut flora due to antibiotics. Novel approaches (preferably antibiotic-free) are urgently needed to address SSI. Surgical site infection is considerably worse in immunocompromised patients where prophylaxis antibiotics are considerably much less effective, even in the case where the infective pathogen is sensitive to the administered antibiotics. Whether or not immune system plays a direct role in boosting prophylaxis antibiotics effectiveness or prophylaxis antibiotics functioning in heightening immune system has not been studied. Rather, reduced antibiotic effectiveness in immunocompromised patients has been blamed on factors, such as therapy-induced neutropenia, or disregulated innate immune responses, and/or impaired neutrophil functions. Driven by our preliminary data, we hypothesize that bacterial killing by prophylaxis antibiotics at the site of infection results in immune system activation which in turn directly boosts the effectiveness of antibiotics by mobilizing immune leukocytes to the site of infection. In aim 1 of this proposal, we will assess the molecular mechanism(s) that couple innate immune system with prophylaxis antibiotics. In aim 2, we will test our hypothesis that immunomodulators -- that can mobilize and activate immune system at the site of infection -- will be effective in controlling surgical site infections even in the absence of prophylaxis antibiotics. We will use an implant and a wound animal models for surgical site infection to evaluate the effectiveness of immunomodulator-based therapies (single vs. in combination with antibiotics) as compared to prophylaxis antibiotics alone in controlling local and systemic infections. We will also assess the possible deleterious side- effects of immunomodulator-based approaches on animal health and normal physiological processes. These comprehensive studies will tackle surgical site infection which is an important public health concern. They will address critical knowledge gaps in our understanding of the direct role that immune system plays in boosting infection control by prophylaxis antibiotics. And they will lay the groundwork for the development of novel immunomodulator-based approaches to control surgical site infections.

免疫系统在预防性抗生素控制手术部位感染中的作用尽管感染控制实践取得了许多进展——包括改善手术室通风、屏障、灭菌方法、改进的手术技术、手术部位感染（SSI）仍然是导致发病率、住院时间延长和死亡，估计每年造成 3.5 至 100 亿美元的损失仅在美国，围手术期预防性抗生素的使用就占医疗支出。（手术前约 1 小时）是大多数外科手术的护理标准，但即使是短期抗生素也是如此。使用与抗生素耐药性的出现以及艰难梭菌风险增加有关感染、免疫和神经系统疾病，其中许多归因于肠道菌群失调迫切需要新的方法（最好是不含抗生素）来解决 SSI。在免疫功能低下的患者中，预防性使用抗生素的手术部位感染要严重得多。即使在感染性病原体对病原体敏感的情况下，其效果也要低得多免疫系统是否在加强预防性抗生素方面发挥直接作用。尚未研究抗生素在增强免疫系统方面的有效性或预防作用。相反，免疫功能低下患者的抗生素有效性降低被归咎于以下因素：治疗引起的中性粒细胞减少症，或先天免疫反应失调，和/或中性粒细胞功能受损。在我们的初步数据的推动下，我们发现了预防性抗生素对细菌的杀灭作用感染导致免疫系统激活，从而直接提高抗生素的有效性将免疫白细胞动员到感染部位在该提案的目标 1 中，我们将评估分子水平。将先天免疫系统与预防性抗生素结合的机制在目标 2 中，我们将测试我们的方法。假设免疫调节剂——可以动员和激活感染部位的免疫系统—— 即使没有预防性抗生素，也能有效控制手术部位感染。用于手术部位感染的植入物和伤口动物模型，以评估其有效性与预防相比，基于免疫调节剂的疗法（单一疗法与抗生素联合疗法）单独使用抗生素来控制局部和全身感染，我们还将评估可能的有害副作用。基于免疫调节剂的方法对动物健康和正常生理过程的影响。这些综合研究将解决手术部位感染这一重要的公共卫生问题。他们将解决我们对免疫系统在疾病中所起的直接作用的理解方面的关键知识差距。通过预防性抗生素促进感染控制，这将为开发抗生素奠定基础。基于免疫调节剂的新型方法来控制手术部位感染。