The joint environment and periprosthetic joint infection

摘要 假体周围关节感染(PJI)是关节置换术后的严重并发症。预防感染 PJI仍然是最好的治疗方法，因为一旦PJI成立，就很难治愈，复发率超过17%。 手术后，关节植入物立即沐浴在术后浆血液(SSF)中。 随着时间的推移，它会变成一种粘稠的、富含蛋白质和蛋白多糖的关节液。我们的数据显示了 滑液(SynF)、血清和血清之间的抗生素敏感性、细菌黏附和髓系细胞功能 血清稀释度接近伤口液/SSF。重要的是，我们的数据表明流体成分 在这一进化过程中，细菌的粘附性、抗生素敏感性都有不同的调节，这意味着， 免疫反应。令人兴奋的是，我们的数据进一步表明，超声触发的微泡的应用 干扰(UTMD)可以影响细菌新陈代谢，以增强因感染而丧失的抗生素敏感性 关节液的演化。因此，我们假设术后SSF存在一个“黄金窗口” 允许通过抗生素和免疫的联合作用来根除污染细菌 响应，而向SynF的过渡限制了两者的疗效。我们进一步提出，这一黄金窗口 可以通过使用UTMD来激活细菌新陈代谢来增强和扩展。我们将(1)确定 SSF和SynF液对抗菌活性和髓系细胞功能的影响，(2)UTMD对小鼠的影响 SSF和SynF关节液细菌清除和髓系功能；(3)体内预防PJI 微泡/抗生素联合治疗。这些信息将被用来创建联合疗法， 将在活体内预防PJI。重要的是，我们的新策略将与当前的临床感染无缝结合 可立即将其转化为预防产后感染的新的治疗方法。

ABSTRACT Peri-prosthetic joint infections (PJI) are devastating complications of joint replacements. Prevention of infection remains the best strategy as once a PJI has established, it is difficult to cure and recurrence rates exceed 17%. Immediately following surgery, the joint implants are bathed in a post-operative serosanguinous fluid (SSF) which over time changes to a viscous, protein- and proteoglycan-rich joint fluid. Our data show differences in antibiotic sensitivity, bacterial adhesion, and myeloid cell function between synovial fluid (SynF), serum, and serum dilutions that approximate wound fluid/SSF. Importantly, our data suggest that the fluid composition across this evolution differentially modulates bacterial adherence, antibiotic sensitivity, and by implication, immune response. Excitingly, our data further suggest that application of ultrasound-triggered microbubble disruption (UTMD) can impact bacterial metabolism to enhance the antibiotic sensitivity that was lost with the evolution of the joint fluid. Thus, we hypothesize that a “golden window” exists in which the post-operative SSF permits eradication of contaminating bacteria through the combined actions of antibiotics and the immune response while the transition to SynF limits the efficacy of both. We further propose that this golden window can be enhanced and extended through the use of UTMD to activate bacterial metabolism. We will (1) determine the effects of SSF and SynF fluid on antibiotic activity and myeloid cell function, (2) determine UTMD effects on bacterial eradication and myeloid function in SSF and SynF joint fluid and (3) prevent PJI in vivo through combined microbubble/antibiotic treatments. This information will be used to create combination therapies that will prevent PJI in vivo. Importantly, our novel strategy will seamlessly integrate with current clinical infection mitigation strategies and can be immediate translated into a new therapeutic approach for prevention of PJI.