OrthoCarolina, Hip and Knee Center, Charlotte, North Carolina.
Department of Orthopaedic Surgery, Cleveland Clinic Florida, Weston, Florida.
J Arthroplasty. 2024 Sep;39(9S1):S229-S235.e1. doi: 10.1016/j.arth.2024.03.069. Epub 2024 Apr 9.
Systemic intravenous antimicrobials yield poor outcomes during treatment of periprosthetic joint infection due to the inability to obtain minimum biofilm eradication concentrations. This study evaluated the safety of a novel method of optimized local delivery of intra-articular antibiotics (IAAs).
This was a Phase II, multicenter, prospective randomized trial evaluating safety of a rapid (seven-day) two-stage exchange arthroplasty with IAA irrigation compared to standard two-stage exchange. The Experimental Group received irrigation using 80 mg tobramycin daily with a 2-hour soak, followed by hourly irrigation using 125 mg vancomycin with a 30-minute soak via an intramedullary irrigation device. The Control Group received an antibiotic-loaded cement spacer with vancomycin (average 8.4 g) and tobramycin (average 7.1 g, total 16 g antibiotics). Both groups received 12 weeks of systemic antibiotics following Stage 2. Safety measures included adverse events, peak vancomycin/tobramycin serum concentrations (Experimental Group), blood transfusion, and mortality. There were thirty-seven patients randomized to the Experimental Group and 39 to control. There was no difference in baseline demographics or comorbidities.
There were no antibiotic medication-related adverse events and 2 serious adverse events related to antibiotic instillation. Of 188 vancomycin peak measurements, 69% had detectable serum level concentrations, with all concentrations well below the maximum acceptable trough threshold of 20 μg/mL. Of the 103 tobramycin peak measurements, 45% had detectable levels, with all below the maximum acceptable peak threshold of 18 to 24 μg/mL. There was no difference in blood transfused per subject (Experimental: 655 mL versus Control: 792 mL; P = .4188). There were two (2) deaths in the Experimental Group and four (4) in the control.
The use of IAA is safe with minimal systemic antibiotic exposure. There was no difference in the rates or severity of serious adverse events between groups. Further research is being conducted to examine treatment efficacy.
由于无法达到最低的生物膜清除浓度，全身静脉使用抗生素在治疗假体周围关节感染时效果不佳。本研究评估了一种新型关节内抗生素（IAAs）局部优化给药方法的安全性。
这是一项二期、多中心、前瞻性随机试验，评估了快速（7 天）两期关节置换术联合 IA 灌洗与标准两期关节置换术相比的安全性。实验组接受每天 80mg 妥布霉素持续浸泡 2 小时，随后使用髓内灌洗装置每小时灌洗 125mg 万古霉素持续浸泡 30 分钟。对照组接受载有万古霉素（平均 8.4g）和妥布霉素（平均 7.1g，共 16g 抗生素）的抗生素水泥间隔器。两组在第二期后均接受 12 周的全身抗生素治疗。安全性措施包括不良事件、万古霉素/妥布霉素的血清峰浓度（实验组）、输血和死亡率。实验组有 37 例患者随机分组，对照组有 39 例。两组患者的基线人口统计学和合并症无差异。
实验组没有发生与抗生素药物相关的不良事件，有 2 例严重不良事件与抗生素灌注有关。在 188 次万古霉素峰浓度测量中，有 69%的患者有可检测到的血清水平，所有浓度均远低于 20μg/ml 的最大可接受谷值阈值。在 103 次妥布霉素峰浓度测量中，有 45%的患者有可检测到的水平，所有水平均低于 18-24μg/ml 的最大可接受峰值阈值。每组接受的输血无差异（实验组：655ml 对对照组：792ml；P=0.4188）。实验组有 2 例死亡，对照组有 4 例死亡。
IAAs 的使用具有安全性，全身抗生素暴露最小。两组之间严重不良事件的发生率或严重程度无差异。正在进行进一步的研究以检查治疗效果。
