Infection Prevention in Total Knee Replacement

全膝关节置换术中的感染预防

• 批准号: 9105679
• 负责人: Joan E Bechtold
• 金额: $ 20.88万
• 依托单位: HENNEPIN HEALTHCARE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-06 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9105679
• 关键词: Accounting; Acute; Animal Model; Antibiotic Therapy; Antibiotics; Bacteriology; Bone Transplantation; Caring; Ceftriaxone; Characteristics; Clinical; Communicable Diseases; Complex; Complication; Cytolysis; Data; Doxycycline; Failure; Foreign-Body Reaction; Formulation; Fracture; Future; Goals; Healed; Health; Healthcare Systems; Histology; Hospitals; Impairment; Implant; Infection; Infection prevention; Inflammation; Joints; Knee joint; Knowledge; Lead; Literature; Measures; Medical; Methods; Microbial Biofilms; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Orthopedics; Osteomyelitis; Outcome; Patient-Focused Outcomes; Patients; Population; Powder dose form; Prevention; Prosthesis; Public Health; Recovery; Recurrence; Regulatory Pathway; Replacement Arthroplasty; Resources; Risk; Rodent Model; Scientist; Sepsis; Serum; Specialist; Spinal Fractures; Staging; Surgeon; System; Testing; Time; Tobramycin; Toxic effect; Training; Translations; Treatment Failure; United States; Work; base; burden of illness; clinical practice; clinically relevant; cohort; controlled release; cost; design; healing; high risk; improved; knee replacement arthroplasty; mortality; multidisciplinary; novel; patient population; prevent; research study; response; sample fixation; tibia

DESCRIPTION (provided by applicant): The overall goal of our work is to decrease the infection rate in total knee arthroplasty (TKA) and reduce the treatment morbidity for those patients with TKA that do become infected, thereby benefitting a large and rapidly growing patient population. Sepsis occurs in 1-3% of primary and 3-7% of revision TKA and is by some accounts already the main reason for revision TKA surgery. Treatment of infected TKA often requires prosthetic revision, and the most successful treatment is a costly and morbid two-stage revision surgery that requires specially trained surgeons, has prolonged recovery and creates a rising burden on the health care system. With over 600,000 TKA performed annually in the United States, this complication is a looming public health problem with significant morbidity and mortality. Our immediate goal is to prevent the establishment of infection following TKA. While achieving this goal will reduce the burden of disease associated with infected TKA, our eventual goal is optimize two-stage revision and to produce a robust and reliable one-stage revision for infected TKA, which would dramatically simplify the treatment of infected TKA and reduce both morbidity and related expense. Our overall strategy is organized with two Specific Aims to evaluate two antibiotic delivery methods (free and controlled) with two antibiotics (tobramycin and doxycycline) in our rodent model of infected TKA. Our hypotheses reflect that evidence of infection with a controlled-release antibiotic delivery method will be less than with free release, which will be less than systemic antibiotic or control (no treatment), and that the antibiotics wil differ in their respective responses. Evidence of infection is based on radiographic score, histology (foreign body reaction, inflammation, bony lysis), and quantitative bacteriology. Specific Aims are coordinated to provide standardized data to enable future optimization studies. Although the R21 does not require preliminary work, we include several studies to demonstrate our expertise in infection modeling, local antibiotic delivery, and with the basic and clinical use of the proposed controlled-delivery system. The knowledge we gain will lead to future work evaluating different antibiotic release characteristics and different bacterial strains in combination with parenteral antibiotics.This all leads to our eventual goal of refining a two-stage and developing a reliable, less costly and less morbid one-stage revision surgery. Our multidisciplinary team of material and basic scientists, practicing joint replacement surgeons and orthopaedic infectious disease specialists, along with our strong preliminary work and institutional focus on orthopaedic infection, provide broad background to carefully design and interpret experiments to improve patient outcome.

描述(申请人提供)：我们工作的总体目标是降低全膝关节置换术(TKA)的感染率，并降低TKA患者的治疗发病率，从而使大量且快速增长的患者受益。脓毒症发生在1-3%的原发TKA和3-7%的翻修全膝关节置换术中，一些人认为这已经是翻修TKA手术的主要原因。感染的TKA的治疗通常需要假体翻修，而最成功的治疗是昂贵且病态的两阶段翻修手术，需要受过专门培训的外科医生，恢复时间长，给医疗保健系统带来越来越大的负担。在美国，每年有超过60万例TKA，这种并发症是一个迫在眉睫的公共卫生问题，具有显著的发病率和死亡率。我们的近期目标是预防全膝关节置换术后感染的发生。虽然实现这一目标将减少与感染的TKA相关的疾病负担，但我们的最终目标是优化两阶段版本，并为感染的TKA产生稳健可靠的一阶段版本，这将极大地简化感染TKA的治疗，并降低发病率和相关费用。我们的总体策略有两个特定的目标来评估两种抗生素给药方法(免费和受控)和两种抗生素(妥布霉素和多西环素)在我们的TKA感染啮齿动物模型中的应用。我们的假设反映了控释抗生素给药方法感染的证据将少于自由释放抗生素给药方法， 这将少于全身抗生素或对照(不治疗)，而且抗生素的反应将有所不同。感染的证据是基于放射记分、组织学(异物反应、炎症、骨质溶解)和定量细菌学。协调具体目标，以提供标准化数据，以便进行未来的优化研究。虽然R21不需要前期工作，但我们包括几项研究，以证明我们在感染建模、局部抗生素给药以及拟议的受控给药系统的基本和临床应用方面的专业知识。我们所获得的知识将导致未来的工作，评估不同的抗生素释放特性和不同的细菌菌株与非肠道抗生素的组合。所有这些都导致我们的最终目标是提炼两个阶段，并开发出可靠的、成本更低、病态更少的一阶段翻修手术。我们由材料和基础科学家组成的多学科团队，从事关节置换外科医生和骨科传染病专家，加上我们对骨科感染的强有力的前期工作和机构关注，为仔细设计和解释实验以改善患者预后提供了广泛的背景。

项目成果

Systemic versus free antibiotic delivery in preventing acute exogenous implant related infection in a rat model.

全身与游离抗生素递送在预防大鼠模型中急性外源性植入物相关感染方面的比较。

• DOI: 10.1002/jor.25052
• 发表时间: 2022
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Marston,Scott;MirickMueller,Gudrun;Sabin,Arick;Hansen,GlenT;Lindgren,Bruce;Aparicio,Conrado;Armstrong,AlexandraR;Larsen,OleH;Schmidt,Andrew;Kyle,Richard;Gustilo,Ramon;Tsukayama,Dean;Bechtold,Joan;Bue,Mats
• 通讯作者: Bue,Mats