The clinical and molecular epidemiology of colistin-resistant carbapenem-resistant Enterobacteriaceae (CRE) in long-term acute care hospitals (LTACHs)

项目摘要 碳青霉烯类耐药肠杆菌科（CRE）的出现和快速传播代表了 公共健康威胁。CRE引起的感染与显著的发病率和死亡率相关，部分原因是 有限的抗生素治疗选择。多粘菌素类，包括粘菌素，是重要的最后一线治疗药物， 用于CRE感染的药物，包括作为可能降低死亡率的联合抗生素方案的一部分。 然而，最近在全球范围内报告了粘菌素耐药CRE（colR-CRE）病例，并代表了一种新的耐药性。 主要的治疗挑战，因为没有经过充分研究的治疗方案。急性病后护理机构， 特别是长期急性护理医院（LTACH），是越来越重要的临床护理场所， 美国的LTACH，由医疗保险和医疗补助服务中心（CMS）定义为 平均住院时间≥25天的急性护理医院的特征是慢性危重病患者， 抗生素暴露率、留置器械使用率和机械通气率较高的人群。这些 这些特征显著增加了该群体中colR-CRE定殖和感染的风险。 在长期急性发作期，colR-CRE的发生率也被放大，这是由于从急性发作期到急性发作期的复杂、高风险转移的融合。 多个急症护理医院到一个设施。由于所有这些原因，长期自来水公司可能是关键， colR-CRE的出现和传播。然而，在临床和实验室研究方面， 分子流行病学的colR-CRE，特别是在LTACH设置。该提案通过了一项 跨学科的方法，并将链接colR-CRE的临床和分子流行病学， 提高对这种高度耐药病原体在LTACH环境中的认识。的具体目标 该建议包括以下内容：目的1：确定colR-CRE定植或感染的风险因素， 目的2：评价colR-CRE定植或感染对LACH患者死亡率的影响。 LTACH设置;目的3：使用全基因组测序前瞻性评价来自 CRE基线患病率高的LTACH区域网络。完成拟议的研究 aims将为CRE中粘菌素耐药性的临床和分子流行病学提供重要见解， 医疗保健越来越重要。阐明colR-CRE的流行病学将显著 为制定有效的感染预防和抗生素管理策略提供信息， 这些生物的出现和传播。此外，更广泛地了解流行病学， LACH中的colR-CRE对于降低高度连接的短期和长期colR-CRE率至关重要， 长期急性护理环境，包括了解LTACH作为出现 colR-CRE。

Project Summary The emergence and rapid spread of carbapenem-resistant Enterobacteriaceae (CRE) represents a major public health threat. Infections due to CRE are associated with significant morbidity and mortality, due in part to limited antibiotic treatment options. The polymyxins, including colistin, are important last-line therapeutic agents for CRE infections, including as part of combination antibiotic regimens that may reduce mortality. However, cases of colistin-resistant CRE (colR-CRE) have been recently reported worldwide, and represent a major therapeutic challenge, as there are no well-studied treatment options available. Post-acute care settings, and long-term acute care hospitals (LTACHs) in particular, are increasingly important sites of clinical care in the United States. LTACHs, which are defined by the Centers for Medicare and Medicaid Services (CMS) as acute care hospitals with an average length of stay of ≥25 days, are characterized by a chronically, critically-ill population with high rates of antibiotic exposure, indwelling device use, and mechanical ventilation. These characteristics significantly increase the risk of colonization and infection with colR-CRE in this population. Rates of colR-CRE are also amplified in LTACHs due to the convergence of complex, high-risk transfers from multiple acute care hospitals to a single facility. For all of these reasons, LTACHs are likely to be critical in the emergence and transmission of colR-CRE. However, there is a significant lack of data on the clinical and molecular epidemiology of colR-CRE specifically in the LTACH setting. This proposal adopts an interdisciplinary approach, and will link the clinical and molecular epidemiology of colR-CRE to substantially improve the understanding of this highly drug-resistant pathogen in the LTACH setting. The Specific Aims of this proposal include the following: Aim 1: To identify risk factors for colonization or infection with colR-CRE in LTACH patients; Aim 2: To evaluate the impact of colR-CRE colonization or infection on mortality in the LTACH setting; Aim 3: To use whole-genome sequencing to prospectively evaluate colR-CRE isolates from a regional network of LTACHs with a high baseline prevalence of CRE. The completion of the proposed research aims will provide critical insights into the clinical and molecular epidemiology of colistin resistance in CRE in a healthcare setting of increasing importance. Elucidation of the epidemiology of colR-CRE will significantly inform the development of effective infection prevention and antibiotic stewardship strategies to limit the emergence and transmission of these organisms. In addition, a broader understanding of the epidemiology of colR-CRE in LTACHs is critical for reducing rates of colR-CRE across highly connected short-term and long- term acute care settings, including understanding the role of LTACHs as sentinel facilities for the emergence of colR-CRE.