ULTRASONIC/ANTIBIOTIC THERAPY--INFECTED IMPLANT IN VIVO

描述：(改编自申请人的摘要)细菌生物膜 医用植入物上的感染极难消除 传统的抗生素疗法。我们实验室的体外实验表明 低频、低强度超声的应用可以提高 抗生素的作用足以使生物膜的生存能力 在短期暴露(2小时)中减少数量级，并且可以 6小时后存活率降至零。对这种特殊情况的治疗 系统检查。这项研究计划的重点是开发一种动物 测试以确定这种增强的抗生素作用是否也将 发生在活体内。具体地说，这项研究将开发一种简单的感染 植入2个生物膜污染的聚合盘的兔模型 在兔子的背部皮下。这只动物将被全身注射 抗生素，其中一个受感染的植入物将暴露在超声波下 不同的频率、功率和持续时间。两个植入物都将是 将确定植入物上的活细菌，并 比较一下。将研究几个实验参数以确定1) 如果增强的杀戮能在动物模型中复制，2)会发生什么？ 最佳参数是为了快速治疗种植体感染。这个 变量为超声波频率(47和500 kHz)、超声波功率 密度(1.0和0.1W.cm2)、超声波暴露时间(6、12、24和 48小时)、感染年龄(24小时和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，这一影响， 长期暴露(24小时和48小时)超声对未感染兔的影响 将对组织进行评估。实验还将寻找病毒传播的迹象 通过检查植入物部位、肺、肝组织的感染 还有肾脏。 这项研究最重要的结果将是知道 体外超声增强抗生素对生物被膜的抑制作用 可以扩展到活着的动物。如果是这样的话，这种疗法有 有可能减轻疼痛并消除对替代手术的需要 对于成千上万患有种植体感染的人来说。

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.