ULTRASONIC/ANTIBIOTIC THERAPY--INFECTED IMPLANT IN VIVO

超声波/抗生素治疗——体内感染的植入物

• 批准号: 2910665
• 负责人: WILLIAM G PITT
• 金额: $ 11.61万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2910665
• 关键词: antibiotics; bacteria infection mechanism; biological models; combination therapy; drug interactions; gram negative bacteria; gram positive bacteria; histology; implant; laboratory rabbit; medical implant science; model design /development; nonhuman therapy evaluation; sound frequency; ultrasound therapy

DESCRIPTION: (Adapted from the applicant's abstract) Bacterial biofilm infections on medical implants are extremely difficult to eliminate using conventional antibiotic therapy. In vitro experiments in our lab have shown that the application of low frequency, low intensity ultrasound can enhance the action of antibiotics sufficiently that the viability of biofilms can be reduced orders of magnitude in short term exposure (2 hrs.), and can be reduced to zero viability after 6 hrs. of treatment for the particular system examine. This research proposal is focused on developing an animal test to determine whether this enhancement of antibiotic action will also occur in vivo. Specifically the research will develop a simple infection model in a rabbit by inserting 2 biofilm-contaminated polymeric disks subcutaneously in the back of the rabbit. The animal will be given systemic antibiotics, and one of the infected implants will be exposed to ultrasound of various frequencies, powers, and durations. Both implants will be recovered and the viable bacteria on the implants will be determined and compared. Several experimental parameters will be studied to determine 1) if the enhanced killing can be reproduced in an animal model, and 2) what the optimal parameters are for quickly treating the implant infections. The variables will be ultrasonic frequency (47 and 500 kHz), ultrasonic power density (1.0 and 0.1 W.cm2), duration of ultrasonic exposure (6, 12, 24, and 48 hrs.), age of infection (24 and 48 hrs.), bacterial species (E. coli and P. aeruginosa), antibiotic (gentamicin and enrofloxacin), and implant material (polyethylene and silicone rubber). In addition, the effect of long term exposure (24 and 48 hrs.) of ultrasound on non-infected rabbit tissue will be assessed. Experiments will also look for signs of spread of the infection by examining tissues taken from the implant site, lungs, liver and kidney. The most significant results of this research will be to know whether the ultrasonically enhanced antibiotic action against biofilms observed in vitro can be extended to living animals. If this is the case, this therapy has potential to relieve the pain and eliminate the need for replacement surgery for thousands of people who have implant infections.

描述：（改编自申请人的摘要）细菌生物膜 使用医疗植入物消除感染极其困难 常规抗生素治疗。 我们实验室的体外实验表明 低频、低强度超声波的应用可以增强 抗生素的作用足以使生物膜的生存能力 短期暴露（2小时）的数量级降低，并且可以 6小时后活力降至零。 针对特定情况的治疗 系统检查。 该研究计划的重点是开发一种动物 测试以确定抗生素作用的增强是否也会 发生在体内。 具体来说，该研究将开发一种简单的感染 通过插入 2 个生物膜污染的聚合物盘在兔子中建立模型 位于兔子背部的皮下。 动物将接受全身治疗 抗生素，其中一个受感染的植入物将接受超声波照射 不同的频率、功率和持续时间。 两种植入物都将 恢复并确定植入物上的活细菌 比较的。 将研究几个实验参数以确定 1) 如果增强杀伤可以在动物模型中重现，2）什么 最佳参数用于快速治疗种植体感染。 这 变量为超声波频率（47 和 500 kHz）、超声波功率 密度（1.0 和 0.1 W.cm2）、超声波暴露持续时间（6、12、24 和 48 小时）、感染年龄（24 和 48 小时）、细菌种类（大肠杆菌和 铜绿假单胞菌）、抗生素（庆大霉素和恩诺沙星）和植入物 材料（聚乙烯和硅橡胶）。 此外，效果 未感染兔子长期暴露于超声波（24 和 48 小时） 将评估组织。 实验还将寻找传播的迹象 通过检查从植入部位、肺、肝脏中取出的组织来确定感染情况 和肾脏。 这项研究最重要的结果是了解是否 超声波增强体外观察到的针对生物膜的抗生素作用 可以扩展到活体动物。 如果是这种情况，这种疗法有 有可能减轻疼痛并消除更换手术的需要 为成千上万患有植入物感染的人提供帮助。