DESCRIPTION: Despite aggressive peri-operative antibiotic treatments, between 1 in 20 and 1 in 100 patients undergoing spinal surgery develop an infection. For patients with traumatic injury, these rates easily exceed 10%. With > 5 million annual surgeries by 2030 and only partially effective infection treatments, the cost and disability due to infection will continue to mount. More effective means to prevent infection are therefore a clinical imperative. To be most effective, new treatments must eradicate pathogens before their adherence to the implant surface attenuates antibiotic and immune susceptibility. Aware of this requirement, our laboratories have long focused on new ways to create antibacterial implant systems that prevent bacterial colonization. Our hypothesis is that maintaining supra-therapeutic antibiotic concentrations at the hardware site during the peri-operative period will prevent establishment of infection and lower infection rates. To test this, we propose to develop a simple porous polyether ether ketone (PEEK) sheath that surrounds the spinal rod and releases its contents--mg quantities of a combination of antibiotics--upon application of ultrasound (US); all antibiotics will be released from sheaths during the peri-operative period to ensure aggressive prophylaxis. Use of antibiotic combinations is expected to minimize antibiotic resistant pathogens and to ensure that all contaminating pathogens are eradicated. There are three specific aims 1: To characterize the stability and release kinetics of an US-activated antimicrobial release system. 2: To test the ability of the sheaths to prevent bacterial colonization of adjacent hardware in vitro. 3: To determine the utility of the sheath in eradicating infection in an in vivo model of infection. The approach detailed in this application ensures eradication of pathogens in the immediate post-operative period. The concept and impetus has arisen through the efforts of a spinal surgeon, US physicist, basic scientist (implant infections), and biomaterials engineer (PEEK and implant retrieval and analysis). It directly addresses the problem of spinal implant infections using innovative applications of proven materials that upon completion of this project can quickly and effectively be translated to the clinical arena. We anticipate that this therapy wil further lower infection rates and ameliorate the pain, suffering, disability, and mortality associated with infections that occur after spinal surgery.