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

免疫系统在预防抗生素手术部位感染控制中的作用 尽管在感染控制实践方面取得了许多进展-包括改善手术室通风，屏障， 消毒方法，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，估计每年花费35亿至100亿美元， 仅美国的医疗保健支出。围手术期预防性抗生素的应用 （手术前约1小时）是大多数外科手术的护理标准。即使是短期抗生素 使用与抗生素耐药性的出现以及艰难梭菌的风险增加有关 感染，免疫和神经系统疾病，其中许多已被归因于生态失调， 肠道植物群。迫切需要新的方法（最好是无药）来解决SSI。 在免疫功能低下的患者中，如果预防性使用抗生素， 即使在感染性病原体对微生物敏感的情况下， 使用抗生素。免疫系统是否在预防性抗生素的增强中起直接作用 有效性或预防性抗生素在增强免疫系统中的作用尚未研究。 相反，免疫功能低下患者中抗生素有效性的降低被归咎于以下因素，例如 治疗诱导的中性粒细胞减少症，或先天免疫应答失调，和/或中性粒细胞功能受损。 根据我们的初步数据，我们假设预防性抗生素在感染部位的细菌杀灭作用， 感染导致免疫系统激活，这反过来又直接提高抗生素的有效性， 将免疫白细胞动员到感染部位。在本提案的目标1中，我们将评估 将先天免疫系统与预防性抗生素偶联的机制。在目标2中，我们将测试我们的 假设免疫调节剂--可以在感染部位动员和激活免疫系统-- 即使在没有预防性抗生素的情况下，也能有效控制手术部位感染。我们将使用 植入物和手术部位感染的伤口动物模型，以评价 与预防性治疗相比，基于免疫调节剂的治疗（单药vs.与抗生素联合） 抗生素单独控制局部和全身感染。我们也会评估可能有害的一面- 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。 这些全面的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免疫系统中所起的直接作用的理解中的关键知识缺口。 通过预防性抗生素加强感染控制。它们将为发展 新的免疫调节剂为基础的方法来控制手术部位感染。

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.