COMMUNITY-ASSOCIATED MRSA COLONIZATION AMONG HIV+ MEN

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。目标1。前瞻性确定城市诊所中HIV+ MSM人群中无症状MRSA定植的患病率、发生率和持续性。大约20%的普通人群和35%的HIV感染者被S.金黄色。虽然与S.金黄色葡萄球菌，通常在前鼻孔，是非常常见的，只有一小部分的殖民者将发展临床感染。HIV+ MSM受最近MRSA感染爆发影响的原因尚不清楚。在MRSA流行和地方性流行的背景下，对HIV+ MSM中MRSA定植的流行率知之甚少。由于定殖先于感染，因此描述沙门氏菌定殖的范围是很重要的。金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌在这一人群和地方爆发已经发生。为了实现这一目标，我们将每6个月进行一次鼻拭子检查，持续一年（共3次），以检测在洛杉矶两个城市HIV诊所接受治疗的患者队列中的MRSA定植。 目标2。前瞻性地确定MRSA在一组HIV感染患者中定植的危险因素。MRSA在HIV+ MSM人群中定植的危险因素尚不清楚。对这次爆发的假设包括疾病相关（如HIV相关的免疫抑制），行为相关（如皮肤接触）和病原体相关（如S。金黄色葡萄球菌毒力因子）。为了实现这一目标，我们将从上述队列中收集HIV+ MSM的详细行为和临床信息。将该人群的风险因素与两组对照组进行比较：非MSM的HIV+人群和未定植MRSA的HIV+ MSM。 目标3。对HIV+ MSM人群中定植的MRSA菌株进行分子分型，并与HIV+ MSM人群中MRSA菌株临床感染情况进行比较，量化该人群中菌株定植的持续性。目前尚不清楚通常定植于HIV+ MSM的菌株是否与引起感染的菌株相似。这个问题具有重要的临床意义，因为消除定植的干预措施可能只需要针对那些可能导致疾病的菌株的人。为了实现这一目标，我们将对定植HIV+ MSM的MRSA分离株进行分子菌株分型，如目标#1所述，并将其与导致住院HIV+ MSM中CA-MRSA感染的菌株进行比较。此外，纵向监测将提供12个月期间每种定殖菌株的持续性数据。 目标4。鉴定定植于HIV+ MSM的MRSA菌株的毒力因子，并将这些菌株与引起HIV+ MSM临床感染的MRSA菌株进行比较。大多数MRSA产生的毒素在临床疾病中的作用仍然没有得到很好的描述。由于各菌株产毒的异质性，金黄色葡萄球菌，比较引起定植和感染的菌株之间的产量将提供关于哪些因素可能对临床感染的发展重要的重要见解。为了实现这一目标，我们将从引起定植和感染的分离株亚组中鉴定毒力因子，以确定哪些因子可能与临床疾病的发展相关。

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.