Epidemiology of CRE and MRSA transmission: patient and organism factors

 描述(由申请人提供)：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)会增加患者的发病率和死亡率。CRE是一种新出现的病原体，易感染ICU患者。MRSA也非常普遍，导致美国大量患者被列入MRSA接触预防措施。接触预防措施可防止耐抗生素细菌在急性护理环境中传播。然而，接触预防措施也可能产生不利影响，包括医护人员就诊频率减少，患者心理症状增加，以及可能发生更严重的不良事件。目前尚不清楚的是，某些患者是否更有可能将抗药性细菌传播给医护人员和随后的患者，如果是这样，这些患者的特征是什么。此外，尚不清楚哪些医护人员与患者之间的互动会导致更大的传播，以及哪些细菌特有的因素会导致更多的传播。这项建议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患者应该采取接触预防措施，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。建议的研究是可行的，因为我们有经验，并使用所有建议的方法发表了报告。我们的假设是，特定的患者特征和特定的医护人员与患者之间的互动会导致更高的传播率，并且所确定的个体风险因素对于CRE和MRSA是独一无二的。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这项应用的目标：目标1和目标2：我们将进行一项多地点、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与患者的互动导致CRE(目标1)和MRSA(目标2)的更大传播。目的3：我们将对AIMS 1和AIMS 2中获得的高传播菌和低传播菌的存储样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的分子特性。拟议工作的意义在于，它将使人们更好地了解与这些细菌传播有关的因素，识别高风险活动和 提供生物标志物，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。这一建议具有创新性，原因如下：a)它探索了抗生素耐药细菌“超级传播者”的新概念，这一概念以前曾被提出过，但从未进行过深入研究；b)在离开房间时培养医护人员的手和手套的替代结果极大地增加了研究的力量，是患者传播的近乎完美的替代结果；以及c)这种结果选择使研究能够以成本效益高的方式在较小的规模上完成。

 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.