Prevention of Biofilm Related Infections Using a Novel, Broad Spectrum Antimicrob

描述（由申请人提供）：骨科植入物相关感染不仅对医疗保健系统来说是昂贵的，而且影响着全世界的患者。这些感染的主要原因是存在于已形成的自然生物膜中的细菌，这些细菌在创伤时或随后的手术中污染开放性骨折部位。为了直接和局部地对抗和预防这些感染，人们研究了种植体的抗生素表面涂层。然而，由于微生物对抗生素的耐药性不断发展，缺乏从种植体表面长期洗脱的特性，并且在许多情况下，对革兰氏阴性和革兰氏阳性细菌的活性谱有限，抗生素仍然具有显着的局限性。因此，需要开发用于骨科植入物的新型抗菌涂层。在此，我们建议研究一种新型抗菌药物-阳离子类固醇抗菌剂-13 (CSA-13)，它对革兰氏阴性和革兰氏阳性细菌具有优异的广谱活性。我们打算使用CSA-13作为骨科固定板的表面涂层，以防止感染。在我们的实验设计中，为了促进强烈的感染信号，我们将建立金黄色葡萄球菌的生物膜生长在CDC生物膜反应器系统上，后者提供了一种创建标准化生物膜的手段。优惠券将插入固定板底部的凹槽中，作为一个整体，固定板/优惠券将直接放置在羊的胫骨表面上。两组变量的求值；csa -13涂层或未涂层、生物膜处理或未处理的种植体将决定这种新型抗菌涂层是否具有对抗和可能预防骨科、生物膜种植体相关感染的潜力。此外，研究的第二阶段将使用氚作为CSA-13的放射性标记物，以确定CSA-13对组织的局部和全身影响。通过闪烁计数和组织学分析，确定CSA-13对组织和骨折愈合的影响。综上所述，本实验旨在首先分析新型CSA-13抗菌药物在已建立的生物膜中对抗和预防由常见的骨科病原体金黄色葡萄球菌引起的骨科植入物相关感染的能力，其次确定CSA-13是否对宿主组织和终末器官有有害影响。我们希望通过这些手段，提高平民和军队创伤患者的骨科创伤护理水平。

DESCRIPTION (provided by applicant): Orthopaedic implant-related infections are not only costly to healthcare systems, but affect patients the world over. Contributing significantly to these infections are bacteria residing in established biofilms of nature that contaminate open fracture sites either at the time of trauma or during subsequent surgery. In an attempt to fight and prevent these infections, directly and locally, antibiotic surface coatings of implants have been investigated. However, antibiotics continue to have significant limitations due to evolving antibiotic resistance by microorganisms, a lack of long-term elution properties from implant surfaces and, in many instances, a limited spectrum of activity against Gram-negative and Gram-positive bacteria. Thus, novel antimicrobial coatings need to be developed for orthopaedic implants. Herein, we propose to investigate a novel antimicrobial - cationic steroid antimicrobial-13 (CSA-13) - which has superior broad-spectrum activity against Gram-negative and Gram-positive bacteria. We intend to use CSA-13 as a surface coating on orthopaedic fixation plates to prevent infection. To promote a strong infection signal in our experimental design, established biofilms of Staphylococcus aureus will be grown on coupons from the CDC biofilm reactor system, the latter provides a means to create standardized biofilms. The coupons will be inserted into a notch in the fixation plate on its underside and as a unit, the fixation plate/coupon will be placed directly onto the surface of the tibia of sheep. The evaluation of two sets of variables; CSA-13-coated or uncoated and biofilm-treated or untreated implants will determine if this novel antimicrobial coatings has the potential to fight and possibly prevent orthopaedic, biofilm implant-related infections. Furthermore, a second phase of the study will use tritium as a radiolabel on CSA-13 to determine the local and systemic effects of CSA-13 on tissue. By scintillation counting and histological analysis, the effects of CSA-13 on tissue and fracture healing will be determined. Taken together, the proposed experiments are designed to analyze first, the ability of the novel CSA-13 antimicrobial to fight and prevent orthopaedic implant-related infection promoted by a common orthopaedic pathogen, S. aureus, in an established biofilm and second, to determine if CSA-13 has detrimental effects on host tissue and end organs. We hope, by these means, to improve the orthopaedic trauma care of both civilian and military trauma patients.