Novel Diagnostics to Improve Antimicrobial Stewardship for Acute Respiratory Tract Infections in Resource-Limited Settings

改善资源有限环境下急性呼吸道感染抗菌药物管理的新型诊断方法

• 批准号: 9314348
• 负责人: GAYANI TILLEKERATNE
• 金额: $ 18.86万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-07 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9314348
• 关键词: Acute; Antibiotic Resistance; Antibiotics; Antigens; Area; Award; Bacterial Infections; Bioinformatics; Biological Assay; Biological Markers; Characteristics; Clinical Trials; Clinical Trials Design; Collaborations; Collection; Communicable Diseases; Country; Diagnosis; Diagnostic; Diagnostic tests; Enrollment; Epidemiology; Etiology; European; Fever; Five-Year Plans; Foundations; Frequencies; Funding; Future; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genomics; Goals; Hospitals; Immune response; Income; Infection; Influenza; Inpatients; Intervention Trial; Knowledge; Laboratories; Language; Legionella pneumophila; Logistic Regressions; Measures; Mentors; Mentorship; Messenger RNA; Microbiology; Minority; Outpatients; Patients; Performance; Peripheral; Physicians; Play; Polymerase Chain Reaction; Population; Positioning Attribute; Reference Standards; Research; Research Infrastructure; Research Personnel; Resources; Respiratory Tract Infections; Role; South Asian; Specificity; Sri Lanka; Streptococcus pneumoniae; Structure; Syndrome; Teaching Hospitals; Technology; Testing; Training; Uncertainty; Universities; Urine; Viral; Whole Blood; Work; adjudicate; antimicrobial; base; cohort; density; genetic signature; global health; improved; novel; novel diagnostics; pathogen; procalcitonin; prospective; respiratory; response; skill acquisition; skills; tertiary care

Project Summary/ Abstract Acute respiratory tract infections (ARTIs) are a leading cause of antibiotic overuse worldwide. Rapid, accurate identification of a pathogen can reduce antibiotic overuse for ARTIs, but is not always possible with available diagnostics. In low- or middle-income countries (LMICs), ARTI diagnosis is further complicated by limited laboratory infrastructure. Previously, the applicant showed that providing access to rapid antigen-based influenza testing in a LMIC setting was associated with a significant decrease in antibiotic use; however, the majority of influenza-positive patients still received antibiotic prescriptions. Physicians later cited diagnostic uncertainty regarding bacterial infection as a major reason for antibiotic over-prescription. To more effectively minimize antibiotic use for ARTIs, diagnostics that broadly classify infections as bacterial or viral may play an important role. The long-term goal of the applicant is to become an independent investigator developing effective strategies for using novel diagnostics to improve antimicrobial stewardship in LMIC settings. The work proposed in this application will be carried out in a LMIC with the objectives of 1) defining the epidemiology of ARTIs, 2) refining a novel host-based gene expression assay that differentiates between viral and bacterial ARTIs, and 3) determining the performance characteristics of procalcitonin and gene signatures at differentiating between viral and bacterial ARTIs. To accomplish these goals, the applicant will carry out the project under the mentorship of experts in genomics, infectious disease diagnostics, antibiotic resistance/ stewardship, and global health. The proposed Specific Aims will be carried out at a tertiary care hospital in Sri Lanka and include the following: 1) Determine the frequency distribution of viral and bacterial respiratory infections among patients with acute febrile respiratory illness, 2) Refine a gene expression classifier to distinguish viral and bacterial ARTIs, and 3) Prospectively enroll a cohort of ARTI patients to assess the performance characteristics of procalcitonin and gene expression classifiers at differentiating between viral and bacterial ARTIs. By conducting this work, the applicant proposes to fill an important gap in knowledge regarding the applicability of host-based technologies for diagnosing ARTIs in a South Asian, LMIC population. The proposed comprehensive five-year plan includes didactic sessions, hands-on laboratory and bioinformatics work, antimicrobial stewardship and clinical trials training, and structured mentorship to develop the candidate as an independent and successful researcher. The completion of these aims and the acquisition of skills during the training period would place the applicant in a competitive position to apply for future R01 funding. By the conclusion of the award period, the applicant will have contributed significantly to the knowledge of how host-based technologies perform at diagnosing ARTIs in a South Asian, LMIC setting, and will be poised to become a leader in developing effective strategies for improving the rational use of antibiotics in resource-limited settings.

项目概要/摘要 急性呼吸道感染（ARTI）是全世界抗生素过度使用的主要原因。快速、准确 识别病原体可以减少 ARTI 中抗生素的过度使用，但现有技术并不总是可行 诊断。在低收入或中等收入国家 (LMIC)，ARTI 诊断由于有限的 实验室基础设施。此前，申请人表明，提供快速基于抗原的途径 中低收入国家的流感检测与抗生素使用的显着减少有关；然而， 大多数流感阳性患者仍然接受抗生素处方。医生后来引用了诊断 细菌感染是抗生素过度处方的主要原因的不确定性。为了更有效地 尽量减少 ARTI 中抗生素的使用，将感染大致分类为细菌或病毒的诊断可能会发挥重要作用 重要作用。申请人的长期目标是成为一名独立研究者，开发 使用新型诊断方法改善中低收入国家抗菌药物管理的有效策略。工作 本申请中提出的研究将在中低收入国家中进行，其目标是 1) 确定流行病学 ARTIs，2) 完善一种新型的基于宿主的基因表达测定，可区分病毒和细菌 ARTI，以及 3) 确定降钙素原和基因特征的性能特征 区分病毒和细菌 ARTI。为了实现这些目标，申请人将执行 该项目由基因组学、传染病诊断、抗生素耐药性专家指导/ 管理和全球健康。拟议的具体目标将在斯里兰卡的一家三级护理医院进行 兰卡并包括以下内容： 1) 确定病毒和细菌呼吸道疾病的频率分布 急性发热呼吸道疾病患者的感染，2) 细化基因表达分类器 区分病毒和细菌 ARTI，以及 3) 前瞻性地招募一组 ARTI 患者来评估 降钙素原和基因表达分类器在区分病毒和病毒方面的性能特征 细菌 ARTI。通过开展这项工作，申请人建议填补知识方面的重要空白 关于基于宿主的技术在南亚、中低收入国家人群中诊断 ARTI 的适用性。 拟议的全面五年计划包括教学课程、实践实验室和 生物信息学工作、抗菌药物管理和临床试验培训以及结构化指导以开发 候选人作为一名独立且成功的研究人员。这些目标的完成和收购 培训期间技能的提高将使申请人在申请未来的 R01 时处于竞争地位 资金。到奖励期结束时，申请人将为 了解基于主机的技术如何在南亚、中低收入国家环境中诊断 ARTI，以及 将成为制定有效策略以改善抗生素合理使用的领导者 在资源有限的环境中。