EPIDEMIOLOGY AND ERADICATION OF MRSA IN HOUSEHOLDS WITH CHILDREN

描述（由申请人提供）：社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）在美国和其他国家流行，并造成重大的健康和经济负担。由于CA-MRSA现在是社区和许多医疗环境中的主要MRSA克隆，临床医生和感染控制从业人员面临着新的挑战。社区现在是一个重要的和不断扩大的水库传播致命的CA-MRSA菌株进入医院，可能会增加医院MRSA感染的严重性。现有的感染预防策略是基于与传统医疗保健相关的耐甲氧西林金黄色葡萄球菌菌株传播相关的风险因素。为了有效地减轻当代CA-MRSA菌株在医疗保健和社区环境中的传播，我们必须首先了解这种流行性克隆的传播动力学，确定与获得和感染相关的因素，并确定环境表面污染在生物体传播中的重要性。 CA-MRSA感染在家庭中的聚集使得这成为研究CA-MRSA传播动力学的合乎逻辑的设置。我们之前的研究显示，MRSA疾病儿童的家庭接触者中MRSA定植的患病率很高，并证明与单独的索引患者的非殖民化相比，所有家庭成员的非殖民化导致索引患者和家庭接触者的皮肤和软组织感染（SSTI）的发生率降低。将招募CA-MRSA感染的儿科患者及其家庭成员参加为期一年的CA-MRSA家庭传播动力学前瞻性自然史研究。通常处理的家用物品和表面，以及宠物狗和猫，将被培养。将在12个月内确定参与者的系列定植状态和感染发生率。将对所有回收的MRSA分离株进行分子分型，以阐明传播的方向性，并确定感染菌株是否类似于内源性定植菌株、从家庭接触中回收的菌株或从环境表面回收的菌株。使用混合效应逻辑回归模型，将阐明多个水平的风险因素（包括家庭定植压力，宿主行为习惯以及家庭表面和宠物的污染）之间的关系，以确定赋予CA-MRSA定植，感染和传播最大风险的因素。随后，研究受试者将被随机分配到一项干预研究中，以比较所有家庭成员进行非殖民化措施（应用鼻莫匹罗星和稀释漂白水浴）与仅对前一年有SSTI病史的家庭成员进行非殖民化措施（在自然史研究期间确定）相比，在预防复发性SSTI方面的有效性。定植状态和感染发生率将再随访12个月。这些研究将为优化干预措施提供信息，以减少CA-MRSA定植和疾病的负担。 公共卫生相关性：社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）是一个重要的公共卫生问题。拟议的研究将确定这些细菌如何在家庭内传播，确定皮肤定植和感染的风险因素，并评估预防CA-MRSA感染的方法。我们的研究结果将有助于改善减少CA-MRSA疾病的方法。

DESCRIPTION (provided by applicant): Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is epidemic in the United States and other countries and poses a significant health and economic burden. As CA-MRSA is now the predominant MRSA clone in the community and in many healthcare settings, clinicians and infection control practitioners face new challenges. The community is now an important and expanding reservoir for the spread of virulent CA-MRSA strains into hospitals, likely increasing the severity of nosocomial MRSA infections. Existing infection prevention strategies are based on risk factors associated with the transmission of traditional healthcare-associated MRSA strains. To effectively mitigate the spread of contemporary CA- MRSA strains in both healthcare and community settings, we must first understand the transmission dynamics of this epidemic clone, identify factors associated with acquisition and infection, and determine the significance of environmental surface contamination in the spread of the organism. The clustering of CA-MRSA infections in households makes this a logical setting in which to study CA- MRSA transmission dynamics. Our prior studies revealed a high prevalence of MRSA colonization in household contacts of children with MRSA disease and demonstrated that decolonization of all household members resulted in a decreased incidence of skin and soft tissue infection (SSTI) in index patients and household contacts compared to decolonization of the index patient alone. Pediatric patients with CA-MRSA infection and their household members will be recruited to participate in a one-year prospective natural history study of CA-MRSA household transmission dynamics. Commonly handled household objects and surfaces, and pet dogs and cats, will be cultured. Serial colonization status and infection incidence in participants will be ascertained over 12 months. Molecular typing will be performed on all recovered MRSA isolates to illuminate the directionality of transmission and to determine whether infecting strains resemble endogenous colonizing strains, strains recovered from household contacts, or strains recovered from environmental surfaces. Using mixed effects logistic regression modeling, the relationships among risk factors at multiple levels (including household colonization pressure, host behavioral practices, and contamination of household surfaces and pets) will be elucidated to identify factors conferring the greatest risks for CA-MRSA colonization, infection, and transmission. Subsequently, study participants will be randomized into an intervention study to compare the effectiveness of decolonization measures (application of nasal mupirocin and dilute bleach water baths) in preventing recurrent SSTI when these measures are performed by all household members compared to decolonizing only household members with a history of SSTI in the prior year (as determined during the natural history study). Colonization status and infection incidence will be followed for an additional 12 months. These studies will inform optimized interventions to reduce the burden of CA-MRSA colonization and disease. PUBLIC HEALTH RELEVANCE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant public health problem. The proposed research will define how these bacteria are transmitted within households, identify risk factors for skin colonization and infection, and evaluate approaches to prevent CA-MRSA infection. Our results will help improve methods to reduce CA-MRSA disease.