Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA.
Antimicrob Agents Chemother. 2013 Oct;57(10):5080-6. doi: 10.1128/AAC.00702-13. Epub 2013 Aug 5.
Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.
治疗人工关节感染通常涉及两阶段的置换，即先移除植入物并放置抗生素间隔物，然后进行全身性抗生素治疗，再延迟重新植入。然而，如果抗生素治疗能够得到改善，那么一期置换或保留植入物可能更为可行，从而降低发病率并保留功能。在这项研究中，使用了一种人工关节感染的小鼠模型，其中金黄色葡萄球菌被接种到膝关节中，膝关节内有一个通过手术放置的金属植入物，从股骨延伸出来。该模型用于评估万古霉素加利福平的联合治疗与单独使用万古霉素相比，对这些感染是否具有更高的疗效。术后第 7 天，保留植入物并使用万古霉素加或不加利福平进行 6 周的治疗。进行体内生物发光成像、体外 CFU 计数、X 射线成像和组织学分析。我们发现，与单独使用万古霉素相比，万古霉素联合利福平具有显著的治疗益处。综上所述，我们的研究结果表明，所使用的小鼠模型可以作为一种有价值的体内临床前模型系统，用于在更广泛的人体研究之前评估和比较抗生素和联合治疗对人工关节感染的疗效。
