PK/PD Evaluation Resistance Development in Caseating Granuloma

干酪样肉芽肿的 PK/PD 评估耐药性发展

• 批准号: 7917381
• 负责人: WILLIAM Ramses BISHAI
• 金额: $ 64.6万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-07 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7917381
• 关键词: Address; Adjuvant Therapy; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Autopsy; Bacteria; Cavia; Clarithromycin; Development; Dexamethasone; Dose; Drug Combinations; Drug resistance; Drug usage; Etanercept; Evaluation; Fiber; Frequencies; Granuloma; High Pressure Liquid Chromatography; Image; Imaging technology; Immunosuppressive Agents; In Situ; In Vitro; Inflammation; Label; Lead; Lesion; Life; Lung; Microbe; Modeling; Mus; Mycobacterium tuberculosis; Necrosis; Oryctolagus cuniculus; Pathologic; Patients; Penetration; Pharmaceutical Preparations; Pharmacodynamics; Photons; Positron; Positron-Emission Tomography; Property; Recombinants; Relative (related person); Resistance; Resistance development; Role; Sampling; Serum; Site; Steroids; System; Testing; Thymidine Kinase; Tissues; Tuberculosis; X-Ray Computed Tomography; bacterial resistance; base; fialuridine; inhibitor/antagonist; novel; tool; tuberculosis treatment

DESCRIPTION (provided by applicant): Active tuberculosis causes lung cavities where TB-bacteria grow to high levels. Cavitary TB is more transmissible to others, harder to treat in the patient who has it, and more likely to lead to drug resistance. This proposal will combine an animal model in which TB cavities reproducibly develop with novel radiologic imaging technologies and traditional pharmacologic tools to determine whether the TB cavity serves as a sanctuary site where bacteria may escape high drug concentrations and develop resistance. The last part of the study will determine whether giving immunosuppressive drugs which block cavity development together with antibiotics is useful in accelerating cure in an animal model of TB.

描述（由申请人提供）：活动性结核病导致肺空洞，结核菌在肺空洞中生长到高水平。空洞性结核病更容易传染给他人，患者更难治疗，而且更有可能导致耐药性。该提议将联合收割机与新型放射成像技术和传统药理学工具结合，以确定结核腔是否作为细菌可能逃避高药物浓度并产生耐药性的避难所。这项研究的最后一部分将确定是否给予免疫抑制药物，阻止腔发展与抗生素一起是有用的，在加速治愈结核病的动物模型。