A Combination Coating for the Prevention of Perioperative Device Infections

用于预防围手术期器械感染的组合涂层

• 批准号: 9026501
• 负责人: Dustin Lee Williams
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9026501
• 关键词: Acute; Address; Adverse effects; Affect; Animal Model; Antibiotic Resistance; Antibiotic Therapy; Bacteria; Bacterial Infections; Chronic; Clinical; Colony-forming units; Control Groups; Data; Devices; Effectiveness; Ensure; Environment; Eukaryotic Cell; Exhibits; Film; Goals; Healthcare Systems; Hospitalization; Hospitals; Implant; In Vitro; Incidence; Infection; Infection Control; Infection prevention; Knowledge; Laboratories; Medical Device; Military Personnel; Modeling; Motivation; Operative Surgical Procedures; Orthopedics; Osteomyelitis; Patient Care; Patients; Perioperative; Phosphate Buffer; Polymers; Population; Predisposition; Prevention; Procedures; Quality of life; Rehabilitation therapy; Reporting; Research; Research Design; Resistance; Running; Saline; Sheep; Signal Transduction; Silicones; Spine surgery; Staging; Staphylococcus aureus; Surface; Suspension substance; Suspensions; Testing; Time; Tissues; Titania; Titanium; United States; Vancomycin-resistant S. aureus; Vertebral column; Veterans; Virulent; Weight; Work; antimicrobial; bacterial resistance; bactericide; biomaterial compatibility; bone; clinical care; combat; controlled release; cost; hip replacement arthroplasty; implant attachment; improved; in vivo; in vivo Model; innovation; killings; knee replacement arthroplasty; methicillin resistant Staphylococcus aureus; patient population; prevent; public health relevance; research study; response; skeletal; skeletal tissue; success; surface coating

DESCRIPTION (provided by applicant): RELEVANCE: Annually, more than 700,000 primary hip and knee replacements and another 1.2 million spine surgeries are performed on VA and non-VA patients in the United States (US). Perioperative device-related infections compromise approximately 2-3% of these primary procedures and when considering revision surgeries, this number grows as high as 17.5%. Infections following these procedures are difficult to treat, especially in cases where antibiotic-resistant bacteria have been identified as the pathogenic species. These resistant bacteria may be present in the form of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), or similar resistant bacterial strains. Estimates of veteran and nonveteran hospital acquired S. aureus and MRSA infections are reported at nearly 500,000 cases in the US each year. This increase in the number of MRSA cases has been attributed to the bacteria's evolving resistance toward conventional antibiotic therapy. OBJECTIVES: The objective of this study is to combat resistant bacterial strain infections associated with common orthopedic device procedures using a unique silicone (Si) polymer released cationic steroidal antimicrobial-13 (CSA-13) in a sheep animal model. The long-term goals of this work are to reduce the incidence of device-related infection, minimize the time required for hospitalization, decrease the expense incurred by the VA Health Care System and patient, and eliminate multiple-stage revision procedures. HYPOTHESES: 1) The 18% weight-to-weight ratio (w/w) CSA-13 in Si polymer combination coating will prevent infection caused by planktonic MRSA in vivo when eluted from the Si polymer coating on a porous coated titanium plug implant. 2) The rate and amount of periprosthetic skeletal attachment within the porous coated region of the plug implant will not be adversely affected by the release of the CSA-13 antimicrobial. PROCEDURES: To test Hypothesis 1 two study groups will be challenged with 200 ¿L of 5x108 colony forming units of planktonic MRSA in phosphate buffered saline. A porous coated titanium (Ti) plug will be implanted into the articulating surface of the right femoral condyle and run for 4 weeks. The infection control (Group 1) will receive a porous coated Ti plug and MRSA suspension to ensure that an infection signal has been generated. The infection challenge (Group 2) will receive a Ti plug coated with a thin film of Si containing the CSA-13 antimicrobial (18% w/w) and MRSA suspension to test the bactericidal efficacy of CSA-13. To test Hypothesis 2 three groups will be utilized to assess the biocompatibility of the CSA-13 combination coating- no MRSA will be used to test Hypothesis 2. The biocompatibility challenge (Group 3) will receive the 18% (w/w) CSA-13/Si coated plug to characterize the effects of CSA-13 on the periprosthetic bone. The polymer control (Group 4) will receive a Si coated plug (without CSA-13) to assess the effects of the polymer, alone, on the adjacent bone to distinguish the effects of CSA-13 from the Si on skeletal attachment. Finally, the biocompatibility control (Group 5) will receive only the porous coated Ti plug-without CSA-13 or Si to demonstrate skeletal attachment in a material with established biocompatibility. Similar to Hypothesis 1 the plug will be implanted in the right femoral condyle and two time points will be utilized to assess biocompatibility: 4 and 24 weeks. SIGNIFICANCE OF FINDINGS: The success of this antimicrobial combination coating has the potential to significantly improve VA clinical care by reducing costs associated with primary and revision surgeries caused by perioperative device related infections. This research would also greatly improve the veteran's quality of life and reduce the time required for hospitalization and rehabilitation by eliminating, or significantly limiting, the veteran's susceptibility to perioperative device related infections.

描述（由申请人提供）： 相关性：每年对美国（美国）的VA和非VA患者进行另外70万主要的髋关节和膝关节置换，另外120万次脊柱手术。围手术期与设备相关的感染损害了这些主要程序的大约2-3％，并且在考虑修订手术时，该数字的增长高达17.5％。遵循这些过程的感染很难治疗，尤其是在抗生素耐药细菌被确定为致病物种的情况下。这些抗性细菌可能以耐甲氧西林的金黄色葡萄球菌（MRSA），抗性金刚霉素金黄色葡萄球菌（VRSA）或类似的抗性细菌菌株的形式存在。每年，美国估计获得了金黄色葡萄球菌和MRSA感染的资深和非兽医医院的估计。 MRSA病例数量的增加归因于该细菌对常规抗生素疗法的耐药性。目的：这项研究的目的是使用独特的硅胶（SI）聚合物释放阳离子类固醇抗菌抗菌13（CSA-13（CSA-13），对抗与常见骨科装置程序相关的抗性细菌菌株感染。这项工作的长期目标是减少与设备相关的感染的发生率，最大程度地减少住院时间，减少VA医疗保健系统和患者产生的费用，并消除多个阶段的修订程序。假设：1）SI聚合物组合涂层中的18％体重与重量比（W/W）CSA-13将防止在多孔涂层钛含量植入物上从SI聚合物涂层中洗脱时，由体内浮游生物MRSA引起的感染。 2）插入植入物多孔涂层区域内的周围骨骼附着的速率和量不会受到CSA-13抗菌抗菌剂的释放的不利影响。程序：要检验假设1两个研究小组将通过在磷酸盐缓冲盐水中的5x108菌落形成的5x108菌落形成单位进行挑战。多孔涂层钛（Ti）塞将植入右股骨con的铰接表面，并运行4周。感染控制（第1组）将接收多孔涂层Ti塞和MRSA悬架，以确保已产生感染信号。感染挑战（第2组）将接收带有含有CSA-13抗微生物的Si薄膜（18％w/w）和MRSA悬浮液的Ti插头，以测试CSA-13的生物学有效性。要测试假设2将使用三个组来评估CSA-13组合涂层的生物相容性 - 无MRSA将用于检验假设2。生物相容性挑战（第3组）将获得18％（W/W）CSA-13/SI涂层，以表征CSA-13对Perip骨的影响。聚合物对照（第4组）将接收SI涂层插头（无CSA-13），以评估聚合物对相邻骨骼的影响，以区分 SI的CSA-13在骨骼附件上。最后，生物相容性控制（第5组）将仅接收带有无CSA-13或SI的多孔涂层Ti插头，以在具有既定生物相容性的材料中演示骨骼附着。类似于假设1插头将被植入 在右股骨con和两个时间点中，将使用两个时间点来评估生物相容性：4和 24周。发现的重要性：这种抗菌组合涂料的成功有可能通过降低与周期性相关感染引起的初级和修订手术相关的成本来显着改善VA临床护理。这项研究还将大大改善退伍军人的生活质量，并通过消除或严重限制退伍军人对定期设备相关感染的敏感性来减少住院和康复所需的时间。