Department of Orthopaedic Surgery, Cleveland Clinic Florida, Weston, Florida.
Department of Orthopaedic Surgery, Cleveland Clinic Adult Reconstruction Research (CCARR), Cleveland Clinic, Cleveland, Ohio; Department of Bioengineering, Cleveland Clinic, Cleveland, Ohio.
J Arthroplasty. 2024 Aug;39(8S1):S2-S8. doi: 10.1016/j.arth.2024.02.044. Epub 2024 Feb 23.
Chronic periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. The underlying pathogenesis often involves the formation of bacterial biofilm that protects the pathogen from both host immune responses and antibiotics. The gold standard treatment requires implant removal, a procedure that carries associated morbidity and mortality risks. Strategies to preserve the implant while treating PJI are desperately needed. Our group has developed an anti-biofilm treatment, PhotothermAA gel, which has shown complete eradication of 2-week-old mature biofilm in vitro. In this study, we tested the anti-biofilm efficacy and safety of PhotothermAA in vivo when combined with debridement, antibiotics and implant retention (DAIR) in a rabbit model of knee PJI.
New Zealand white rabbits (n = 21) underwent knee joint arthrotomy, titanium tibial implant insertion, and inoculation with Xen36 (bioluminescent Staphylococcus aureus) after capsule closure. At 2 weeks, rabbits underwent sham surgery (n = 6), DAIR (n = 6), or PhotothermAA with DAIR (n = 9) and were sacrificed 2 weeks later to measure implant biofilm burden, soft-tissue infection, and tissue necrosis.
The combination of anti-biofilm PhotothermAA with DAIR significantly decreased implant biofilm coverage via scanning electron microscopy compared to DAIR alone (1.8 versus 81.0%; P < .0001). Periprosthetic soft-tissue cultures were significantly decreased in the PhotothermAA with DAIR treatment group (log reduction: Sham 1.6, DAIR 2.0, combination 5.6; P < .0001). Treatment-associated necrosis was absent via gross histology of tissue adjacent to the treatment area (P = .715).
The addition of an anti-biofilm solution like PhotothermAA as a supplement to current treatments that allow implant retention may prove useful in PJI treatment.
慢性人工关节周围感染(PJI)是全关节置换术的主要并发症。其潜在发病机制通常涉及细菌生物膜的形成,这种生物膜可以保护病原体免受宿主免疫反应和抗生素的影响。金标准治疗需要取出植入物,而该程序会带来相关的发病率和死亡率风险。因此,迫切需要寻找一种既能保留植入物又能治疗 PJI 的策略。我们的团队开发了一种抗生物膜治疗方法 PhotothermAA 凝胶,该方法在体外研究中显示可以完全消除 2 周龄成熟生物膜。在这项研究中,我们在兔膝关节 PJI 模型中测试了 PhotothermAA 与清创术、抗生素和保留植入物(DAIR)联合使用时的抗生物膜疗效和安全性。
新西兰白兔(n=21)膝关节切开,钛胫骨植入物插入,胶囊关闭后接种 Xen36(生物发光金黄色葡萄球菌)。2 周后,兔子接受假手术(n=6)、DAIR(n=6)或 PhotothermAA 联合 DAIR(n=9),2 周后处死,测量植入物生物膜负担、软组织感染和组织坏死。
与单独使用 DAIR 相比,抗生物膜 PhotothermAA 联合 DAIR 可通过扫描电子显微镜显著降低植入物生物膜覆盖率(1.8 比 81.0%;P<0.0001)。与单独使用 DAIR 相比, PhotothermAA 联合 DAIR 治疗组的假体周围软组织培养物明显减少(对数减少:Sham 1.6、DAIR 2.0、联合 5.6;P<0.0001)。通过治疗区域附近组织的大体组织学检查,未见治疗相关坏死(P=0.715)。
在允许保留植入物的当前治疗方法的基础上,添加 PhotothermAA 等抗生物膜溶液可能对 PJI 治疗有用。