Metagenomic Studies of MRSA Colonization

描述(由申请人提供)： 我们的微生物群，即体内和身上的微生物集合，对我们的健康很重要。它还藏匿着机会性病原体，如耐甲氧西林金黄色葡萄球菌(MRSA)。“非殖民化”是一项快速增长的战略，旨在预防由新的医疗保健政策倡议推动的MRSA感染，例如强制监测文化和医疗保健相关感染的公开报告。非殖民化涉及在皮肤或粘膜表面应用靶向或非靶向抗菌剂。鉴于我们的微生物群作为感染屏障的作用，非殖民化方案可能会产生意想不到的负面后果。我们的初步微生物群落特征数据表明，革兰氏阴性杆菌(GNB)是前鼻孔微生物群的一部分，特别是在疗养院居住的成年人。Cochrane最近的一项荟萃分析表明，使用革兰氏阳性抗菌剂莫匹罗星鼻腔非殖民化增加了金黄色葡萄球菌以外的生物(包括GNB)感染的风险。革兰氏阴性杆菌对多种药物的耐药性越来越强，目前正在开发的治疗它们的新型抗菌药很少。因此，将感染从革兰氏阳性病原体转移到革兰氏阴性病原体的干预措施可能会对患者产生长期的负面后果。在一项临床试验中，我们建议研究有和没有当前暴露在医疗环境中的人群的前鼻孔和后咽的微生物组：(A)居住在社区的MRSA定居的成年人和(B)居住在疗养院的MRSA定居的成年人。然后，我们将比较两个人群中个体在基线和非殖民化方案鼻腔注射莫匹罗星和外用洗必泰后的微生物群落。我们的总体假设是，这些地点的微生物组成和对非殖民化的反应因生活环境而异，非殖民化导致重新殖民，革兰氏阴性杆菌的比例增加。这项建议将预防MRSA感染这一临床上重要的问题与一种新的方法--利用16S rRNA基因的高通量焦磷酸测序进行微生物群落分析--联系起来。我们的短期目标是确定这些日益使用的旨在特别控制MRSA的非殖民化方案是否会导致促进致病性革兰氏阴性杆菌定居的次要负面影响。这将对用于感染控制目的的莫匹罗星的使用产生影响。这项研究的长期目标是利用获得的信息开发新的交互作用，在医疗保健过程中操纵人类微生物群，以降低MRSA感染的风险，并将负面后果降至最低。

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.