Department of Orthopaedic Research and Biotechnology, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Division of Medical Sciences, University of Oxford, Oxford, UK.
J Orthop Res. 2020 Sep;38(9):2065-2073. doi: 10.1002/jor.24618. Epub 2020 Feb 11.
Infection of orthopedic implants is a growing clinical challenge to manage due to the proliferation of drug-resistant bacterial strains. In this study, we aimed to investigate whether the treatment of implants with ceragenin-90 (CSA-90), a synthetic compound based on endogenous antibacterial peptides, could prevent infection in a novel rat model of periprosthetic joint infection (PJI) challenged with either local or systemic Staphylococcus aureus. A novel preclinical model of PJI was created using press-fit porous titanium implants in the distal femur of male Wistar rats. Sterile implants were pre-treated with 500 μg CSA-90 in saline. S. aureus was applied either directly at the time of surgery or administered via tail vein injection immediately afterward. Animals were monitored daily for clinical and radiographic evidence of infection for a total of 6 weeks. Post-study microbiological, radiographic, and histological analysis were performed to determine the incidence of PJI and assess osseointegration. CSA-90 treated groups demonstrated a reduced rate of PJI as confirmed by deep tissue swab culture at the time of cull compared with untreated groups with both local (33% vs 100%; P = .009) and systemic (10% vs 90%; P < .0001) S. aureus inoculation. Median survival time also increased from 8 to 17 days and from 8 to 42 days, respectively. In conclusion, this study describes a novel preclinical model of local and hematogenous PJI using a porous metal implant. CSA-90 reduced the incidence of PJI in this model supporting its further development as an antimicrobial coating for orthopedic implants.
由于耐药性细菌株的增多，骨科植入物感染成为一个日益严峻的临床挑战。在这项研究中，我们旨在研究使用合成的内源性抗菌肽衍生化合物ceragenin-90（CSA-90）处理植入物是否可以预防局部或全身金黄色葡萄球菌感染新型假体周围关节感染（PJI）大鼠模型中的感染。我们使用雄性 Wistar 大鼠股骨远端的压配合多孔钛植入物创建了一种新型 PJI 临床前模型。无菌植入物先用生理盐水预处理 500μg CSA-90。金黄色葡萄球菌要么在手术时直接应用，要么在手术后立即通过尾静脉注射。动物每天监测临床和放射影像学感染的证据，总共 6 周。研究结束后进行微生物学、放射影像学和组织学分析，以确定 PJI 的发生率并评估骨整合。与未处理组相比，CSA-90 处理组的深部组织拭子培养在处死时确认 PJI 发生率降低，局部（33%比 100%；P=0.009）和全身（10%比 90%；P<0.0001）金黄色葡萄球菌接种均如此。中位存活时间也分别从 8 天增加到 17 天和从 8 天增加到 42 天。总之，本研究使用多孔金属植入物描述了局部和血源性 PJI 的新型临床前模型。CSA-90 降低了该模型中 PJI 的发生率，支持其作为骨科植入物的抗菌涂层进一步发展。
