PATHOGENESIS AND TREATMENT OF BACTERIAL ENDOPHALMITIS

细菌性内炎的发病机制和治疗

• 批准号: 3261339
• 负责人: TRAVIS A MEREDITH
• 金额: $ 20.65万
• 依托单位: THE EYE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3261339
• 关键词: Bacillus cereus; Pseudomonas aeruginosa; Staphylococcus epidermidis; Staphylococcus infection; bacterial toxins; beta lactam antibiotic; combination chemotherapy; corticosteroids; disease /disorder model; drug administration routes; drug metabolism; endotoxins; exotoxins; eye disorder chemotherapy; eye pharmacology; gram negative bacteria; gram positive bacteria; host organism interaction; inflammation; laboratory rabbit; microorganism immunology; model design /development; tissue /cell culture; uveitis; virulence; vitrectomy; vitreous body

The fundamental thesis of this application is that the final damage to the eye from endophthalmitis is a result of two contributing sets of events: 1) microbial infection consisting of bacterial replication with the release of bacterial products such as toxins and cell wall components; and 2) the host response to infection including the inflammatory response which may in an exaggerated form contribute to tissue damage. We will pursue lines of investigation to examine aspects of both sets of factors. Bacterial infections created by Bacillus spp. and gram-negative bacteria will be examined in a quantitative fashion to test the ability of bacterial cell walls and various products of the bacteria such as endotoxin, necrotic exotoxin, and cereolysin to induce intraocular inflammation alone and in combination. We have identified a bactericidal effect in the vitreous induced by infection with S. epidermidis and by inflammation created by heat-killed S. epidermidis. We will attempt to further characterize this effect, identify whether it is cellular mediated alone or the result of an elaborated factor, and isolate this factor if appropriate. We will examine strategies to enhance bacterial killing in the vitreous by defining the pharmacokinetics of the current antibiotics of choice for intravitreal injection, and testing the synergistic effects of antibiotic combinations and surgery. We will search for successful strategies to modulate the inflammatory response to infection including examining the potential role of agents to block specific factors which create inflammation of unusual severity after infection with certain bacteria.

这个应用程序的基本论点是，对 眼内炎的眼睛是由两组事件引起的： 1)微生物感染，包括细菌与 释放毒素和细胞壁成分等细菌产品；以及 2)宿主对感染的反应，包括炎症反应 这可能会以夸张的形式导致组织损伤。我们会 遵循调查路线，检查这两组因素的各个方面。 由芽孢杆菌引起的细菌感染。和革兰氏阴性菌 将以定量的方式进行检查，以测试 细菌细胞壁和细菌的各种产物，如 内毒素、坏死性外毒素和脑溶素诱导眼内 单独发炎和合并发炎。我们发现了一种杀菌剂 表皮葡萄球菌和沙门氏菌感染对玻璃体的影响 由热致死的表皮葡萄球菌引起的炎症。我们将尝试 进一步描述这种效应，确定它是否是由细胞介导的 单独或由精心设计的因素造成的，并在以下情况下隔离该因素 恰如其分。我们将研究加强细菌杀灭的策略 通过定义当前抗生素的药代动力学来确定玻璃体 玻璃体内注射的选择，并测试协同效应 抗生素组合和手术。我们将寻找成功的 调节感染的炎症反应的策略包括 研究药物在阻断特定因素方面的潜在作用 感染某些病毒后引起异常严重的炎症 细菌。