COMMUNITY-ASSOCIATED MRSA COLONIZATION AMONG HIV+ MEN

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目的#1.前瞻性地确定城市诊所中HIV+MSM中无症状MRSA定植的流行率、发生率和持久性。大约20%的普通人口和35%的艾滋病毒感染者带有金黄色葡萄球菌。虽然金黄色葡萄球菌的定植非常常见，尤其是在前鼻孔，但只有一小部分被定植的人会发展为临床感染。HIV+MSM受到近期MRSA感染暴发影响的原因尚不清楚。在流行和地方性MRSA流行的背景下，对HIV+MSM中MRSA定植的流行情况知之甚少。由于定植先于感染，因此重要的是描述金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌在该人群和暴发地区的定植范围。为了解决这一目标，我们将在一年内每6个月进行一次鼻拭子(总共3次)，以检测在洛杉矶两家城市艾滋病毒诊所接受护理的患者队列中MRSA的定植情况。目的#2.前瞻性地在描述良好的HIV感染患者队列中确定MRSA定植的危险因素。艾滋病毒+男男性接触者中MRSA定植的危险因素尚不清楚。这次暴发的假设包括与疾病有关的(如艾滋病毒相关的免疫抑制)、与行为有关的(如皮肤接触)和与病原体有关的(如金黄色葡萄球菌毒力因子的存在)。为了达到这一目的，我们将从上述队列中收集HIV+MSM的详细行为和临床信息。来自这一人群的危险因素将与2组对照组的风险因素进行比较：HIV+非MSM人群和HIV+MSM非MRSA殖民地人群。目的#3.对HIV+MSM分离的MRSA菌株进行分子分型，并与临床感染的MRSA菌株进行比较，以量化HIV+MSM人群中MRSA菌株定植的持久性。目前尚不清楚通常在HIV+MSM中定居的菌株是否与导致感染的菌株相似。这个问题具有重要的临床意义，因为根除殖民的干预措施可能只针对那些有可能导致疾病的菌株的人。为了达到这个目的，我们将按照AIM#1的描述，对定居在HIV+MSM中的MRSA分离株进行分子菌株分型，并将它们与在住院的HIV+MSM中引起CA-MRSA感染的菌株进行比较。此外，纵向监测将提供每一种定植菌株在12个月期间的持久性数据。目的#4.鉴定HIV+MSM中MRSA株的毒力因子，并与引起HIV+MSM临床感染的MRSA株进行比较。大多数MRSA产生的毒素在临床疾病中的作用仍未得到很好的描述。由于金黄色葡萄球菌的毒素产生是异质性的，比较引起定植和感染的菌株的毒素产生将提供重要的见解，哪些因素可能在临床感染的发展中起重要作用。为了解决这一目标，我们将表征引起定植和感染的一组分离物的毒力因素，以确定哪些因素可能与临床疾病的发展有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aim #1. To prospectively determine the prevalence, incidence, and persistence of asymptomatic MRSA colonization among HIV+ MSM in an urban clinic setting. Approximately 20% of general population and 35% of HIV-infected persons are colonized with S. aureus. Although colonization with S. aureus, typically in the anterior nares, is very common, only a small proportion of colonized persons will develop clinical infections. The reasons that HIV+ MSM have been affected of recent MRSA infection outbreaks remain unclear. There is little known about the prevalence of MRSA colonization among HIV+ MSM in the settings of epidemic and endemic MRSA. Since colonization precedes infection, it is important to describe the scope of colonization with S. aureus and MRSA in this population and in locales where outbreaks have been occurring. To address this aim we will perform nasal swabs every 6 months for one year (3 in total) to detect MRSA colonization from a well-described cohort of patients receiving care in two urban HIV clinics in Los Angeles. Aim #2. To prospectively identify risk factors for MRSA colonization among a well described cohort of HIV-infected patients. Risk factors for MRSA colonization among HIV+ MSM remain unclear. Hypotheses for this outbreak include disease-related (such as HIV-associated immunosuppression), behavioral-related (such as skin to skin contact), and pathogen-related (such as the presence of S. aureus virulence factors). To address this aim we will collect detailed behavioral and clinical information from HIV+ MSM from the above described cohort. Risk factors from this population will be compared to those of 2 groups of controls: HIV+ persons who are not MSM, and HIV+ MSM who are not colonized with MRSA. Aim #3. To molecularly type colonizing MRSA strains from HIV+ MSM and compare them with MRSA strains clinical infection among HIV+ MSM, and to quantify the persistence of strain colonization in this population. It is unclear if strains that commonly colonize HIV+ MSM are similar to those causing infections. This question has important clinical relevance as interventions to eradicate colonization may need to only target those persons with strains likely to cause disease. To address this aim, we will perform molecular strain typing on MRSA isolates colonizing HIV+ MSM, as described in Aim #1 and compare them to strains causing CA-MRSA infection among hospitalized HIV+ MSM. Additionally, longitudinal surveillance will provide data on the persistence of each colonizing strain over a 12-month period. Aim #4. To identify virulence factors from MRSA strains colonizing HIV+ MSM and compare these strains to MRSA strains causing clinical infection among HIV+ MSM. The role that most MRSA-produced toxins have in clinical disease remains poorly described. Because toxin production is heterogeneous among S. aureus, comparing production among strains causing colonization and infection will provide important insights as to which factors may be important in for the development of clinical infections. To address this aim, we will characterize virulence factors from a subset of isolates causing colonization and infection to determine which factors may be associated with the development of clinical disease.