Mycobacterial Lung Diseases in Virginia: sequencing and clinical determinants of relapse and outcome

弗吉尼亚分枝杆菌肺病：复发和结果的测序和临床决定因素

• 批准号: 10321219
• 负责人: ERIC R HOUPT
• 金额: $ 67.54万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10321219
• 关键词: Address; Algorithms; Antibiotics; Applications Grants; Area; Bioinformatics; Biological Assay; Biology; Chimera organism; Clinical; Collaborations; Data; Disease; Drug Kinetics; Drug Monitoring; Drug Tolerance; Drug resistance; Environment; Environmental Microbiology; Environmental Risk Factor; Epidemiology; Exposure to; Future; Genotype; Genus Mycobacterium; Health; Household; In Vitro; Infection; Infection Control; Lung diseases; Mathematics; Measures; Microbial Biofilms; Modification; Morbidity - disease rate; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium intracellulare; Organism; Outcome; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phenotype; Predisposition; Regimen; Relapse; Request for Applications; Research; Resistance profile; Resolution; Role; Sample Size; Serum; Soil; Source; Specimen; Sum; Triage; United States National Institutes of Health; Universities; Ursidae Family; Virginia; Water; absorption; clinical application; clinical sequencing; cohesion; cohort; drug development; evidence base; genome sequencing; improved; in vivo; indexing; individual patient; innovation; innovative technologies; molecular diagnostics; mortality; mycobacterial; non-tuberculosis mycobacteria; novel therapeutics; pharmacokinetics and pharmacodynamics; predict clinical outcome; predictive marker; prognostication; programs; respiratory; tool; whole genome

PROJECT SUMMARY / ABSTRACT Nontuberculous mycobacterial lung diseases, primarily due to M. avium complex (MAC), is an increasing clinical problem nationwide and now overtakes domestic TB in terms of morbidity and mortality. It is also harder to treat and results in poorer outcomes despite longer drug regimens. In this context NIH issued a notice AI-17-016 to request applications for NTM diseases. Here we present a proposal from the University of Virginia, with collaborators at the Virginia Department of Health and Virginia Tech, that addresses many of the needs that were cited. First, we will perform whole genome sequencing of MAC isolates from all of our state's MAC lung disease patients to discern relapse versus reinfection and the environmental sources of acquisition. Second we will utilize a state-wide cohort of new MAC lung disease patients to correlate clinical outcomes with MAC species, drug susceptibility, serum drug levels, and biofilm bioassay. Innovation includes the use of a state-wide epidemiological cohort, exquisite resolution with extensive preliminary data of whole genome sequencing to discern species and mixed infections, a comprehensive state-wide serum drug monitoring program (as we have done already for TB), and expertise in molecular diagnostics and genotypic-phenotypic correlations. In sum, for this most vexing clinical problem of MAC lung disease we bring to bear extensive preliminary data, unique expertise, innovative technology, cohesive collaborations, and synergistic aims.

项目概要/摘要 主要由鸟分枝杆菌复合体 (MAC) 引起的非结核分枝杆菌肺部疾病日益增多 全国范围内的临床问题，目前其发病率和死亡率已超过国内结核病。这也是 尽管药物治疗方案较长，但仍难以治疗并导致较差的结果。在此背景下，NIH 发布了 通知 AI-17-016 请求 NTM 疾病申请。在这里，我们提出了来自大学的提案 弗吉尼亚州与弗吉尼亚州卫生部和弗吉尼亚理工大学的合作者解决了许多问题 所引用的需求。首先，我们将对来自本州所有菌株的 MAC 分离株进行全基因组测序。 MAC 肺病患者辨别复发与再感染以及感染的环境来源。 其次，我们将利用全州范围内的新 MAC 肺病患者队列将临床结果与 MAC 种类、药物敏感性、血清药物水平和生物膜生物测定。创新包括使用 全州流行病学队列，精细的分辨率和广泛的全基因组初步数据 测序以辨别物种和混合感染，全面的全州血清药物监测 计划（正如我们已经为结核病所做的那样），以及分子诊断和基因型表型方面的专业知识 相关性。总之，针对 MAC 肺病这个最棘手的临床问题，我们采取了广泛的措施 初步数据、独特的专业知识、创新技术、紧密的合作和协同目标。