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 耐碳青霉烯类肠杆菌科细菌(CRE)的出现和迅速传播是一种主要的 公共卫生威胁。由于CRE引起的感染与显著的发病率和死亡率有关，部分原因是 抗生素治疗选择有限。多粘菌素，包括粘菌素，是重要的最后治疗药物。 CRE感染剂，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，对粘菌素耐药的CRE(ColR-CRE)病例最近在世界范围内被报道，并代表了一种 主要的治疗挑战，因为目前还没有经过充分研究的治疗方案。急性后护理环境， 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。LTACH，由医疗保险和医疗补助服务中心(CMS)定义为 急性护理医院的平均住院时间为≥25天，其特点是慢性危重病人 抗生素暴露率、留置装置使用率和机械通气率高的人群。这些 这些特征显著增加了在该人群中定居和感染Colr-Cre的风险。 由于复杂的、高风险的转移从 将多家急救医院合并到一家机构。由于所有这些原因，LTACH很可能在 Col-Cre的发生和传播。然而，关于临床和临床的数据仍然非常缺乏。 在LTACH环境中特异性COR-CRE的分子流行病学。本提案通过了一项 跨学科方法，并将把Colr-CRE的临床和分子流行病学与实质上联系起来 在LTACH环境中提高对这种高度耐药病原体的理解。的具体目标 这项建议包括以下内容：目标1：确定在中国定居或感染柯尔-卡介苗的危险因素 目的2：评估Colr-Cre定植或感染对长寿期脑出血患者死亡率的影响。 LTACH环境；目标3：使用全基因组测序来前瞻性地评估来自 慢性阻塞性肺病基线患病率较高的长期致死性环芳烃区域网络。拟议研究的完成情况 AIMS将为克雷斯汀耐药的临床和分子流行病学研究提供重要的见解。 医疗保健环境日益重要。阐明Colr-CRE的流行病学将具有重要意义 告知制定有效的感染预防和抗生素管理战略，以限制 这些生物的出现和传播。此外，更广泛地了解流行性感冒的流行病学 LTACH中的Colr-CRE对于降低高度连接的短期和长期网络中的Colr-CRE比率至关重要 术语急性护理环境，包括了解LTACH作为哨兵设施的作用 科尔-克雷。