IMMUNOGLOBULIN COATINGS TO PREVENT CATHETER INFECTION

免疫球蛋白涂层可预防导管感染

• 批准号: 2423523
• 负责人: ANTHONY G. GRISTINA
• 金额: $ 10万
• 依托单位: GAMMA-A TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2423523
• 关键词: Pseudomonas aeruginosa; Staphylococcus epidermidis; adsorption; antibacterial agents; bacterial disease; biomaterial compatibility; biomaterial development /preparation; catheterization; disease /disorder prevention /control; drug delivery systems; drug resistance; drug screening /evaluation; immunoglobulin G; laboratory mouse; laboratory rabbit; molecular film; polypropylenes

Catheters are one of the most commonly used biomaterial implants, (200 million annually in the U.S.). In long term use as for vascular central lines, the urinary tract and peritoneal dialysis, catheters are particularly susceptible to infection. These infections are resistant to antibiotic treatment and persist until removal of the device. Utilizing the concept of Passive Local Immunotherapy, (PLI), we have demonstrated in animal models that biomaterial associated bacterial infections can be prevented through the direct local application of Human immunoglobulin, (IgG), natural antibodies, to biomaterial surfaces. Immunoglobulins in situ opsonize bacteria on arrival or shortly thereafter. Bacteria are identified and targeted for neutrophil and macrophage phagocytosis and killing while bacteria numbers are low and before they can propagate, release toxins, destroy tissue and form protective biofilms. IgG. also neutralizes bacterial toxins. The objective of this study is to demonstrate the efficacy in vitro and in vivo of local IgG coatings to catheter materials in blocking adhesion, colonization and biofilm type infection by clinically relevant strains of S. epidermidis and P. aetuginosa. The IgG prophylaxis/therapeutic is known to be safe (viral inactivated and FDA approved for i.v.use). Advantages of IgG coatings over current treatments are broad spectrum efficacy,independent of antibiotic resistance mechanisms (e.g. methicillin and vancomycin resistant Staphylococci), and cost- effectiveness. PROPOSED COMMERCIAL APPLICATION: The coating of catheters with IgG preparations will increase their resistance to bacterial infection. The New England Journal of Medicine attributes 50,000 deaths a year in the U.S. to catherization procedures at a cost exceeding $1.2 billion.

导管是最常用的生物材料植入物之一(200 在美国每年有100万人)。长期使用，如血管中枢 输尿管、尿路和腹膜透析、导尿管 特别容易受到感染的。这些感染是有抗药性的 进行抗生素治疗，并持续到取出设备为止。 利用被动局部免疫疗法(PLI)的概念，我们有 在动物模型中证明了生物材料相关细菌 感染可以通过直接局部涂抹 人免疫球蛋白，天然抗体，生物材料 表面。免疫球蛋白在到达时原位调理细菌或 不久之后。确定细菌并将其定位于中性粒细胞 巨噬细胞吞噬和杀灭细菌数量较少 在它们繁殖、释放毒素、破坏组织和形成 保护性生物膜。免疫球蛋白。还能中和细菌毒素。这个 本研究的目的是证明其在体外和体内的疗效。 体内局部免疫球蛋白涂层对导管材料的封堵粘连， 临床相关菌株的定植与生物膜型感染 和金黄色葡萄球菌(P.aetuginosa)。免疫球蛋白的预防/治疗 已知是安全的(病毒灭活，FDA批准静脉注射使用)。 与目前的治疗方法相比，免疫球蛋白涂层的优点是广谱的 药效，独立于抗生素耐药机制(例如 耐甲氧西林和万古霉素的葡萄球菌)，以及成本- 有效性。 建议的商业应用： 在导管上涂上免疫球蛋白制剂将增加他们的 抵抗细菌感染。《新英格兰医学杂志》 美国每年有5万人死于插管手术 耗资超过12亿美元。