背景:慢性假体周围关节感染(PJI)是全关节置换术的主要并发症。潜在的发病机理通常涉及保护病原体免受宿主免疫应答和抗生素两者的细菌生物膜的形成。黄金标准治疗需要移除植入物,具有相关发病率和死亡率风险的程序。迫切需要在治疗PJI时保留植入物的策略。我们小组开发了一种抗生物膜疗法,光热AA凝胶,这表明在体外完全根除了两周大的成熟生物膜。在这项研究中,我们测试了体内光热AA与清创术联合使用时的抗生物膜功效和安全性,抗生素,在兔膝关节PJI模型中的植入物保留(DAIR)。
方法:新西兰大白兔(n=21)进行膝关节关节切开术,钛胫骨植入物插入,胶囊闭合后接种Xen36(生物发光金黄色葡萄球菌)。两周后,兔子接受假手术(n=6),DAIR(n=6),或光热AA与DAIR(n=9),并在两周后处死以测量植入物生物膜负荷,软组织感染,和组织坏死。
结果:与单独的DAIR相比,通过扫描电子显微镜,抗生物膜PhotothermAA与DAIR的组合显着降低了植入物生物膜覆盖率(1.8对81.0%;P<0.0001)。在PhotothermAA和DAIR治疗组中,假体周围软组织培养显著降低(对数降低:Sham1.6,DAIR2.0,组合5.6;P<0.0001)。通过与治疗区域相邻的组织的大体组织学观察,没有与治疗相关的坏死(P=0.715)。
结论:添加抗生物膜溶液如PhotothermAA作为当前治疗的补充,允许植入物保留可能在PJI治疗中被证明是有用的。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.