PATHOGENESIS AND TREATMENT OF BACTERIAL ENDOPHALMITIS

本申请的基本论点是， 眼内炎是两组事件的结果： 1)微生物感染，包括细菌复制， 释放细菌产物，如毒素和细胞壁成分;以及 2)宿主对感染的反应包括炎症反应 其可能以夸大的形式导致组织损伤。 我们将 进行调查，以审查这两组因素的各个方面。 由芽孢杆菌属引起的细菌感染。和革兰氏阴性菌 将以定量方式进行检查，以测试 细菌细胞壁和细菌的各种产物， 内毒素、坏死性外毒素和脑溶素诱导眼内 炎症单独和组合。 我们发现了一种杀菌剂 玻璃体内感染S.表皮和通过 热灭活的S.表皮 我们将尝试 进一步表征这种效应，确定它是否是细胞介导的 单独或一个精心设计的因素的结果，并隔离此因素，如果 适当 我们将研究提高细菌杀灭率的策略， 通过定义当前抗生素的药代动力学， 玻璃体内注射的选择，并测试协同效应 抗生素联合疗法和手术 我们将寻找成功的 调节对感染的炎症反应的策略，包括 研究药物阻断特定因素的潜在作用， 在感染某些病毒后， 细菌

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.