Hospital-Acquired Mupirocin-Resistant MRSA in Post-Partum Women and Newborns

产后妇女和新生儿中医院获得的莫匹罗星耐药 MRSA

• 批准号: 8266207
• 负责人: Sharon Beth Brodie Wright
• 金额: $ 49.74万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8266207
• 关键词: Hospital; Acquired; Mupirocin; Resistant; MRSA

DESCRIPTION (provided by applicant): Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of significant morbidity among hospitalized and community-dwelling persons. Initially described as a hospital- and healthcare-associated pathogen, new strains of community-associated MRSA (CA-MRSA) have emerged as an important cause of infection among of community-dwelling individuals. More recently CA-MRSA, as defined by pulsed-field gel electrophoresis, a form of "DNA fingerprinting", has become a growing cause of healthcare-acquired infection. A large outbreak of infection caused by a highly pathogenic strain of CA-MRSA (USA300-0114) occurred at a large urban teaching hospital among post-partum women and newborns soon after discharge. Resistance to mupirocin was noted in a large proportion of isolates during the outbreak, which was an unusual and unexpected finding. Risk factors for colonization and infection with hospital-associated strains of MRSA (HA-MRSA) are fairly well established, but the risk factors for CA-MRSA colonization and infection in this high risk population remain poorly defined. By the use of novel, advanced statistical modeling, the current study aims to delineate the risk factors for colonization and infection with mupirocin-resistant and mupirocin-susceptible strains of CA-MRSA USA300-0114 during this outbreak. Given the dynamic nature of the newborn nursery, the setting in which transmission is suspected to have occurred, transmission dynamics and transmission rates will be determined using an open Susceptible-Infected-Recovered model. Finally, laboratory studies to determine the genetic makeup and other characteristics of the colonizing and infecting MRSA isolates will be performed in parallel with the clinical epidemiological investigations with the aim of determining mechanisms by which resistance to topical antimicrobial agents is spread and possible linkage between pathogen virulence and resistance. The proposed study will examine risk factors for colonization and infection in this population, however, some of the findings will likely be generalizable to CA-MRSA transmission in other populations both in the outbreak and non-outbreak setting. Furthermore, important information regarding development of resistance and mechanisms of resistance to topical agents commonly used in decolonization will be obtained. This information will ultimately have implications for the use of these agents in routine infection control and decolonization. PUBLIC HEALTH RELEVANCE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), in particular MRSA clone USA300-0114, has rapidly become the most common cause of purulent skin and soft tissue infections in the United States. While initially associated with predominantly community-based disease and transmission, this pathogen has entered the hospital setting and now is a common cause of hospital-associated infection. The largest and most protracted outbreak of CA-MRSA infection among post-partum women and newborns occurred at a large urban teaching hospital in the fall of 2008 and continued through summer of 2010, with continued sporadic cases of carriage (nasal and skin) without infection since that time. The majority of infections were caused by MRSA USA300-0114, the most common strain of CA-MRSA. A high rate of resistance to mupirocin, an antibiotic used to eliminate carriage of MRSA, was noted. This study will investigate the epidemiologic risk factors predisposing to CA-MRSA colonization and infection among post-partum women and newborns. By using advanced statistical modeling techniques including time- series analysis, we will study risk factors associated with colonization and infection with CA-MRSA, and in particular colonization and infection with mupirocin-resistant CA-MRSA. In order to link the epidemiologic findings to the molecular and microbiological characteristics of the infecting bacteria recovered during this outbreak, analysis of plasmid DNA will be performed to determine the unique genetic features of the bacteria that may have enhanced the transmission of mupirocin resistance, enabled the acquisition of genetic elements imparting resistance to chlorhexidine and facilitated colonization during this outbreak.

说明(申请人提供)：耐甲氧西林金黄色葡萄球菌(MRSA)是住院和社区居民发病的重要原因。新的社区相关耐甲氧西林金黄色葡萄球菌(CA-MRSA)最初被描述为医院和医疗保健相关的病原体，现已成为社区居民感染的重要原因。最近，根据脉冲场凝胶电泳的定义，CA-MRSA已成为医疗保健获得性感染的一个日益增长的原因。城市某大型教学医院在产后妇女和新生儿出院后迅速暴发高致病性CA-MRSA(USA300-0114)菌株感染。在暴发期间，在很大一部分分离物中发现了对莫匹罗星的耐药性，这是一个不同寻常和意想不到的发现。医院相关耐甲氧西林金黄色葡萄球菌(HA-MRSA)定植和感染的危险因素已经相当明确，但在这一高危人群中CA-MRSA定植和感染的危险因素仍不明确。通过使用新的、先进的统计模型，本研究旨在描述这次暴发期间耐莫匹罗星和敏感莫匹罗星的CA-MRSA USA300-0114菌株的定植和感染的风险因素。鉴于新生儿托儿所的动态性质，怀疑发生传播的环境，传播动态和传播率将使用开放的易感感染-感染-康复模型来确定。最后，将在临床流行病学调查的同时进行实验室研究，以确定定植和感染MRSA分离株的基因组成和其他特征，目的是确定对局部抗菌剂的耐药性传播的机制，以及病原体毒力和耐药性之间可能的联系。拟议的研究将审查该人群中定居和感染的危险因素，然而，其中一些发现可能会推广到在暴发和非暴发环境中的其他人群中的CA-MRSA传播。此外，还将获得有关对非殖民化中常用的局部药物的抗药性发展和抗药性机制的重要信息。这一信息最终将对这些药物在常规感染中的使用产生影响。 控制和非殖民化。 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)，特别是MRSA克隆USA300-0114，已迅速成为美国化脓性皮肤和软组织感染的最常见原因。虽然最初主要与以社区为基础的疾病和传播有关，但这种病原体已进入医院环境，现在是医院相关感染的常见原因。产后妇女和新生儿中最大和最持久的CA-MRSA感染暴发于2008年秋季在一家大型城市教学医院，并持续到2010年夏天，自那时以来继续有零星的携带者(鼻部和皮肤)病例，没有感染。大多数感染是由最常见的CA-MRSA菌株MRSA USA300-0114引起的。注意到对莫匹罗星的耐药率很高，莫匹罗星是一种用于消除MRSA携带的抗生素。本研究将调查产后妇女和新生儿中CA-MRSA定植和感染的流行病学危险因素。通过使用先进的统计建模技术，包括时间序列分析，我们将研究与CA-MRSA定植和感染相关的风险因素，特别是与对莫匹罗星耐药的CA-MRSA定植和感染相关的风险因素。为了将流行病学结果与此次疫情中发现的感染细菌的分子和微生物学特征联系起来，将进行质粒DNA分析，以确定细菌的独特遗传特征，这些特征可能增强了莫匹罗星耐药性的传播，使人们能够获得赋予洗必泰耐药性的遗传要素，并促进了此次疫情期间的定植。