Metagenomic Studies of MRSA Colonization

描述（由申请人提供）： 我们的微生物组，我们身体上和体内的微生物集合，对我们的健康很重要。它也窝藏机会致病菌，如耐甲氧西林的S。金黄色葡萄球菌（MRSA）。“非殖民化”是一种快速发展的战略，以防止MRSA感染，这是由新的医疗保健政策倡议推动的，例如强制性的监测文化和医疗保健相关感染的公共报告。去定殖涉及将靶向或非靶向抗菌剂应用于皮肤或粘膜表面。鉴于我们的微生物组作为感染屏障的作用，去殖民化方案可能会产生意想不到的负面后果。我们初步的微生物群落分析数据表明，革兰氏阴性杆菌（GNB）是前鼻孔微生物组的一部分，特别是在养老院居住的成年人中。最近的一项科克伦荟萃分析表明，鼻内莫匹罗星（一种革兰氏阳性抗菌剂）的去殖民化增加了除沙门氏菌外的微生物感染的风险。金黄色葡萄球菌，包括GNB。革兰氏阴性杆菌的多重耐药性日益严重，目前正在开发的治疗革兰氏阴性杆菌的新型抗菌剂很少。因此，将感染从革兰氏阳性病原体转变为革兰氏阴性病原体的干预措施可能对患者产生长期的负面影响。在一项临床试验中，我们建议研究当前暴露于和未暴露于医疗环境的人群中前鼻孔和后咽的微生物组：（a）MRSA定植的社区居住成人和（B）MRSA定植的疗养院居住成人。然后，我们将比较两个人群中个体在基线和鼻内莫匹罗星和局部洗必泰去殖民化方案后的微生物群落。我们的总体假设是，这些部位的微生物组成和对去殖民化的反应因生活环境而异，去殖民化导致革兰氏阴性杆菌比例增加的再殖民化。该提案将临床上重要的问题，MRSA感染的预防与一种新的方法，使用16S rRNA基因的高通量焦磷酸测序的微生物群落分析联系起来。我们的短期目标是确定这些越来越多地用于控制MRSA的去殖民化方案是否会导致促进致病性革兰氏阴性杆菌定植的继发性负面影响。这将影响莫匹罗星用于感染控制目的。这项研究的长期目标是利用获得的信息开发新的干预措施，在医疗保健期间操纵人类微生物组，以降低MRSA感染的风险，并将负面后果降至最低。 公共卫生相关性： VHA致力于通过国家VA MRSA预防计划预防MRSA感染。这项倡议使用监测文化，以确定与MRSA殖民退伍军人。许多退伍军人和医疗保健提供者希望使用“去殖民化”方案根除MRSA殖民化。考虑到我们正常的植物群或微生物组作为感染屏障的作用，去殖民化方案可能会产生意想不到的负面后果，特别是通过将我们的植物群转向革兰氏阴性细菌。本项目的目的是描述鼻内莫匹罗星和局部洗必泰去殖民化前后MRSA定植退伍军人的正常植物群。我们的长期目标是利用获得的信息开发新的方法来操纵人类微生物组，以降低MRSA感染的风险。

DESCRIPTION (provided by applicant): Our microbiome, the collection of microorganisms on and in our bodies, is important to our health. It also harbors opportunistic pathogens such as methicillin-resistant S. aureus (MRSA). "Decolonization" is a rapidly growing strategy to prevent MRSA infections fueled by new healthcare policy initiatives such as mandated surveillance cultures and public reporting of healthcare associated infections. Decolonization involves the application of targeted or non-targeted antimicrobials to the skin or mucosal surfaces. Given the role of our microbiome as a barrier to infection, decolonization regimens could have unintended negative consequences. Our preliminary microbial community profiling data suggests that Gram-negative bacilli (GNB) are part of the microbiome of the anterior nares, particularly in nursing home dwelling adults. A recent Cochrane meta-analysis showed that decolonization with intranasal mupirocin, a Gram-positive antimicrobial agent, increases the risk of infections due to organisms other than S. aureus including GNB. Gram-negative bacilli are increasingly multi-drug resistant and few novel antimicrobials are under development to treat them. Thus, interventions that shift infections from Gram-positive to Gram-negative pathogens could potentially have long term negative consequences for patients. In a clinical trial, we propose to study the microbiome of the anterior nares and posterior pharynx in populations with and without current exposure to the healthcare environment: (a) MRSA-colonized, community-dwelling adults and (b) MRSA-colonized, nursing home-dwelling adults. We will then compare the microbial communities at baseline and after a decolonization regimen of intranasal mupirocin and topical chlorhexidine within individuals in both populations. Our overall hypothesis is that the microbial composition of these sites and the response to decolonization vary by the living environment and that decolonization leads to re-colonization with an increasing proportion of Gram- negative bacilli. This proposal links a clinically important problem, the prevention of MRSA infections, with a novel methodology, microbial community profiling using high-throughout pyrosequencing of the 16S rRNA gene. Our short term goal is to determine if these increasingly used decolonization regimens targeted at controlling MRSA in particular may result in a secondary negative effect of promoting colonization with pathogenic Gram-negative bacilli. This would have an impact on the use of mupirocin for infection control purposes. The long term goal of this research is to use the information gained to develop novel intervantions to manipulate the human microbiome during healthcare to reduce the risk of MRSA infections with minimized negative consequences. PUBLIC HEALTH RELEVANCE: The VHA is committed to preventing MRSA infections with the national VA MRSA Prevention Initiative. This Initiative uses surveillance cultures to identify veterans colonized with MRSA. Many veterans and healthcare providers want to eradicate MRSA colonization using "decolonization" regimens. Given the role of our normal flora or microbiome as a barrier to infection, decolonization regimens could have unintended negative consequences particularly by shifting our flora towards Gram-negative bacteria. The goal of this project is to characterize the normal flora of MRSA- colonized veterans before and after decolonization with intranasal mupirocin and topical chlorhexidine. Our long term goal is to use the information gained to develop new ways to manipulate the human microbiome to reduce the risk of MRSA infections.