ULTRASONIC/ANTIBIOTIC THERAPY--INFECTED IMPLANT IN VIVO

描述：（改编自申请人摘要）细菌生物膜 医疗植入物上的感染极难消除， 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存活力可以 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。 治疗具体 系统检测 这项研究计划的重点是开发一种动物 测试以确定这种抗生素作用的增强是否也将 发生在体内。 具体来说，这项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圆盘， 在兔子的背部皮下注射。 动物将接受全身性 抗生素，其中一个受感染的植入物将暴露于超声波 不同的频率功率和持续时间 两种植入物都将 回收并确定植入物上的活菌， 比较了 将研究几个实验参数以确定1） 如果增强的杀伤力可以在动物模型中重现，以及2）什么 最佳参数是用于快速治疗植入物感染。 的 变量为超声频率（47和500 kHz）、超声功率 密度（1.0和0.1 W.cm2）、超声暴露持续时间（6、12、24和 48小时），感染年龄（24和48小时），细菌种类（E. 杆菌和 P.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， 长期暴露（24和48小时）对未感染的兔子进行超声检查 将对组织进行评估。 实验还将寻找传播的迹象， 通过检查从植入部位、肺、肝 和肾脏。 这项研究最重要的结果将是知道是否 体外观察超声增强对生物膜的抗菌作用 可以扩展到活体动物。 如果是这种情况，这种疗法 缓解疼痛并消除置换手术需求的潜力 为成千上万的植入物感染患者提供治疗。

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.