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

长期急症护理医院 (LTACH) 中耐粘菌素、耐碳青霉烯类肠杆菌 (CRE) 的临床和分子流行病学

• 批准号: 10642805
• 负责人: EBBING LAUTENBACH
• 金额: $ 74.6万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10642805
• 关键词: Address; Adopted; Antibiotic Therapy; Antibiotics; Case/Control Studies; Characteristics; Chronic; Clinical; Clinical Data; Clinical Management; Cohort Studies; Colistin; Combined Antibiotics; Complex; Critical Illness; Data; Development; Drug resistance; Enterobacteriaceae Infections; Epidemiology; Evolution; Genes; Geographic Locations; Geography; High Prevalence; Infection; Infection prevention; Knowledge; Length of Stay; Link; Mechanical ventilation; Mediating; Molecular Epidemiology; Morbidity - disease rate; New Agents; Organism; Outcome; Patient-Focused Outcomes; Patients; Pattern; Plasmids; Play; Polymyxins; Population; Predisposition; Prevalence; Public Health; Regimen; Reporting; Research; Research Proposals; Risk; Risk Factors; Role; Sample Size; Sentinel; Series; Therapeutic; Therapeutic Agents; United States; United States Centers for Medicare and Medicaid Services; acute care; antimicrobial; carbapenem resistance; carbapenem-resistant Enterobacteriaceae; clinical care; clinical epidemiology; clinical research site; colistin resistance; drug resistant pathogen; effective therapy; electronic medical record system; genome sequencing; health care settings; high risk; hospital care; hospital patient care; hospital readmission; implantable device; improved; individual patient; insight; interdisciplinary approach; mortality; patient population; primary outcome; prospective; resistance mechanism; resistant Klebsiella pneumoniae; transmission process; whole genome

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.

项目摘要 抗碳青霉烯的肠杆菌科（CRE）的出现和迅速传播代表一个主要 公共卫生威胁。由于CRE引起的感染与明显的发病率和死亡率有关，部分原因是 有限的抗生素治疗选择。包括colistin在内的多碳素是重要的最后一线疗法 CRE感染的药物，包括作为可能降低死亡率的组合抗生素方案的一部分。 但是，最近在全球范围内报道了抗毒素的Cre（Colr-cre）病例，并代表 主要的治疗挑战，因为没有经过深入研究的治疗选择。急性后护理设置， 尤其是长期急性护理医院（LTACHS），是越来越重要的临床护理场所 美国。 ltachs，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长期，批判性的 抗生素暴露率高，使用设备的使用和机械通气的人群。这些 特征显着增加了该人群中Colr-Cre的定殖和感染的风险。 由于复杂的高风险转移的收敛性，Colr-Cre的速率也会在LTACHS中扩增 多个急诊医院到一个设施。由于所有这些原因，ltachs可能在 Colr-Cre的出现和传播。但是，关于临床和 COLR-CRE的分子流行病学专门在LTACH环境中。该提案采用了 跨学科方法，并将Colr-Cre的临床和分子流行病学与基本上联系 提高对LTACH环境中这种高度药物耐药性病原体的理解。具体目的 该提案包括以下内容：目标1：确定殖民地或Colr-Cre感染的危险因素 LTACH患者；目标2：评估Colr-Cre殖民或感染对死亡率的影响 ltach设置；目的3：使用全基因组测序来预期评估来自A的Colr-Cre分离株 LTACHS的区域网络具有较高的CRE基线患病率。拟议研究的完成 AIMS将为CRE中CRE的临床和分子流行病学提供关键的见解。 医疗保健设置越来越重要。阐明Colr-Cre流行病学将显着 告知有效的感染预防和抗生素管理策略的发展，以限制 这些生物的出现和传播。此外，对流行病学的更广泛理解 LTACHS中的Colr-Cre对于降低高度连接的短期和长期相连的Colr-Cre速率至关重要 任期急性护理环境，包括了解LTACHS作为哨兵设施的作用 Colr-Cre。