Epidemiology of CRE and MRSA transmission: patient and organism factors

 描述（由申请方提供）：耐碳青霉烯类肠杆菌科（CRE）和耐甲氧西林金黄色葡萄球菌（MRSA）增加患者发病率和死亡率。CRE是新出现的病原体，对ICU患者有偏好。MRSA也非常普遍，导致美国大量患者被置于MRSA的接触预防措施。接触预防措施可防止急性护理环境中耐药细菌的传播。然而，接触预防措施也可能产生不良影响，包括医护人员就诊频率降低、患者心理症状增加以及潜在的更严重不良事件。目前尚不清楚的是，某些患者是否更有可能将耐药细菌传播给医护人员和随后的患者，如果是，这些患者的特征是什么。此外，目前尚不清楚的是，哪些医护人员与患者的相互作用会导致更大的传播，哪些细菌特异性因素会导致传播增加。本提案的总体目标是探索与这些细菌传播相关的因素和潜在的生物标志物，以帮助确定哪些CRE和MRSA患者应采取接触预防措施，哪些可能需要加强预防措施，哪些可能不需要接触预防措施。拟议的研究是可行的，因为我们有经验，并已使用所有提出的方法发表。我们的假设是，某些患者的特征和某些医护人员与患者的相互作用导致更高的传播，并且确定的个体风险因素对于CRE和MRSA是独特的。我们计划测试我们的中心假设，从而通过追求以下三个具体目标来实现本申请的目标：目标1和2：我们将进行多中心、不同地理区域的队列研究，以确定哪些患者风险因素和医护人员-患者相互作用导致CRE（目标1）和MRSA（目标2）的更大传播。目标3：我们将对目标1和2中获得的高传播细菌和低传播细菌的储存标本进行全基因组测序，以确定导致观察到的传播差异的细菌分子特性。拟议工作的重要性在于，它将导致更好地了解与这些细菌传播有关的因素，确定高风险活动， 提供生物标志物，以帮助确定哪些CRE和MRSA患者应采取接触预防措施，哪些可能需要加强预防措施，哪些可能不需要接触预防措施。该提议是创新的，原因如下：a）它探索了先前已经提出但从未深入研究过的耐药细菌的“超级传播者”的新概念; B）在房间出口时培养医护人员的手和手套的替代结果大大增加了研究的效力，并且是患者传播的近乎完美的替代结果;以及c）这种结果选择允许以具有成本效益的方式在较小规模上进行研究。

 DESCRIPTION (provided by applicant):Carbapenem-resistant Enterobacteriaceae (CRE) and methicillin-resistant Staphylococcus aureus (MRSA) increase patient morbidity and mortality. CRE are emerging pathogens with a predilection for ICU patients. MRSA also is extremely prevalent, leading to a large number of patients in the United States being placed on contact precautions for MRSA. Contact precautions prevent the spread of antibiotic-resistant bacteria in the acute-care setting. However, contact precautions may also have adverse effects, including a decreased frequency of healthcare worker visits, increased psychological symptoms of patients, and potentially more serious adverse events. What is not known is if certain patients are more likely to transmit antibiotic-resistant bacteria to healthcare workers and subsequent patients, and if so, what characteristics identify these patients. In addition, what is not known is which healthcare worker-patient interactions lead to greater transmission and which bacterial-specific factors lead to increased transmission. The overall objective of this proposal is to explore factor associated with transmission of these bacteria and potential biomarkers to help determine which patients with CRE and MRSA should be placed on contact precautions, which may need enhanced precautions, and which may not need contact precautions. The proposed research is feasible because we have experience and have published using all of the methodologies proposed. Our hypothesis is that certain patient characteristics and certain healthcare worker-patient interactions lead to higher transmission and that the individual risk factors identified wil be unique for CRE and MRSA. We plan to test our central hypothesis and, thereby, accomplish the objective of this application by pursuing the following three specific aims: Aims 1 and 2: We will perform a multi-site, diverse geographic region cohort study to determine which patient risk factors and healthcare worker-patient interactions lead to greater transmission of CRE (aim 1) and MRSA (aim 2). Aim 3: We will perform whole genome sequencing on stored specimens obtained in aims 1 and 2 for high- transmission bacteria and low-transmission bacteria to determine molecular properties of the bacteria that result in observed differences in transmission. The significance of the proposed work is that it will lead to greater understanding of the factors associated with transmission of these bacteria, identifying high risk activities and provide biomarkers to help determine which patients with CRE and MRSA should be placed on contact precautions, which may need enhanced precautions, and which may not need contact precautions. This proposal is innovative for the following reasons: a) It explores the novel concept of "superspreaders" of antibiotic-resistant bacteria, which has been suggested previously, but never studied in depth; b) The surrogate outcome of culturing healthcare workers hands and gloves upon room exit greatly increases the power of the study and is a near-perfect surrogate outcome for patient transmission; and c) This outcome choice allows the study to be done in a cost-effective manner on a smaller scale.