Clinical Impact of Anti-TB Drug Levels and M. Tuberculosis Susceptibility

描述（由申请人提供）： 摘要 PI：HEYSELL，SCOTT K 项目：1 K23 AI 099019 -01标题：抗结核药物水平和M.结核病易感性登记号：3398392 ================== 注意事项：本摘要摘自应用程序，未经SRA验证。当应用程序扫描过程出现问题时，提取的文本可能不正确或不完整。 ================== 在全球范围内，尽管进行了多药治疗，但仍有高达20%的结核病（TB）治疗失败。在弗吉尼亚州，我们发现糖尿病是延迟反应的一个重要危险因素。在我们在坦桑尼亚的合作地点，与药物敏感性结核病患者相比，耐多药（MDR）结核病患者的死亡风险增加。在这两种情况下，我们都发现结核病药物的血清药物水平较低，但在管理结核病中最好使用血清药物水平仍不清楚。为了告知这个问题，我们已经开发了TB药物活性测定，该测定用在TB治疗时的患者的血浆或血清及其自体TB分离物进行，其允许分离物的药物水平和相对抗性的度量。因此，在本提案中，我们将比较（1）药物水平，（2）M。结核病药物敏感性（MIC），和（3）结核病药物活性测定，以相关的治疗结果的风险，穷人的治疗失败-糖尿病患者在弗吉尼亚州和那些与耐多药结核病在坦桑尼亚。该提案利用了现有的国家结核病控制倡议，即糖尿病患者的早期药物水平监测和剂量调整，并将进一步在坦桑尼亚耐多药结核病转诊医院Kibong'oto国家结核病医院建立一个耐多药结核病患者队列。通过NIH结核病易感性R 01、NIH/Fogarty UVA-坦桑尼亚培训补助金和弗吉尼亚州卫生部，为该提案的各个方面提供了积极的资金和基础设施。我的职业发展计划包括指导、研究生水平的课程和诊断开发、现场研究、结核病药理学和耐多药结核病队列设计方面的出版基准。完成这份提案将使我成为这些领域的独立调查员。

DESCRIPTION (provided by applicant): Abstract PI: HEYSELL, SCOTT K Project: 1K23AI099019-01 Title: Clinical Impact of Anti-TB Drug Levels and M. Tuberculosis Susceptibility Accession Number: 3398392 ================== NOTICE: THIS ABSTRACT WAS EXTRACTED FROM APPLICATION AND HAS NOT BEEN PROOFED BY AN SRA.WHEN THERE ARE PROBLEMS WITH THE APPLICATION SCANNING PROCESS, THE EXTRACTED TEXT MAY BE INCORRECT OR INCOMPLETE. ================== Worldwide tuberculosis (TB) treatment failure occurs in up to 20% of individuals despite multidrug therapy. In Virginia we have found diabetes to be a significant risk factor for delayed response. At our collaborative site in Tanzania, patients with multidrug-resistant (MDR)-TB are at increased risk of death compared to those with drug-susceptible TB. In both settings we have found low serum drug levels to TB medications, however the best use of serum drug levels in managing TB remains unclear. To inform this problem we have developed a TB drug activity assay that is performed with a patient's plasma or serum while on TB therapy and their autologous TB isolate that allows a metric of both drug levels and relative resistance of the isolate. In this proposal, therefore, we will compare (1) drug levels, (2) M. tuberculosis drug susceptibility (MIC), and (3) the TB drug activity assay to relevant treatment outcomes in patients at risk of poor treatment failure- diabetics in Virginia and those with MDR-TB in Tanzania. The proposal leverages an existing state TB control initiative of early drug level monitoring and dose adjustment in diabetics, and will further establish a cohort of MDR-TB patients at Kibong'oto National TB Hospital, the Tanzanian referral hospital for MDR-TB. Active funding and infrastructure for all aspects of the proposal exist through an NIH R01 for TB susceptibility, an NIH/Fogarty UVA-Tanzania Training Grant, and the Virginia Department of Health. My career development plan includes mentorship, graduate level coursework, and publication benchmarks in diagnostic development, field research, TB pharmacology, and MDR-TB cohort design. Completion of this proposal will allow me to become an independent investigator in these fields.