Chu Stacey, Chen Nita, Dang Alexis B C, Kuo Alfred C, Dang Alan B C
1Geisel School of Medicine at Dartmouth College, West Lebanon, NH.
Albany Medical College, School of Medicine, Albany NY.
Int J Spine Surg. 2017 Apr 4;11(2):12. doi: 10.14444/4012. eCollection 2017.
The use of topical vancomycin is increasingly popular in spine surgery. Large retrospective reviews suggest that topical vancomycin provides a cost-effective decrease in post-operative infection. Currently, there is little that is known about the maximum dose that can be applied locally. When 1 gram of vancomycin is mixed into the bone graft and another 1 gram applied freely in a spine wound, the local concentration of antibiotic ranges from 260-2900 μg/mL in the immediate post-op period and 50-730 μg/mL by the second post-operative day. We hypothesized that exuberant doses of vancomycin would be toxic to mesenchymal stem cells (MSCs).
Bone marrow was obtained from the femoral canal of patients undergoing routine elective total hip arthroplasty. Mesenchymal stem cells were isolated using plastic adhesion. Cells were exposed to a wide range of doses of vancomycin for 24 hours and then assessed for viability. Osteogenic potential was assessed with alizarin red staining.
There was dose-dependent cell death with vancomycin use. MSC death was 9.43% at 400 μg/mL (p=0.047), 13.79% at 1600 μg/mL (p=0.0047), 19.35% at 3200 μg/mL (p<0.0001), 24.82% at 6400 μg/mL (p<0.0001) and 51.83% at 12800 μg/mL of vancomycin (p<0.0001) in comparison to the control group containing no vancomycin.
Our in vitro study suggests that vancomycin has toxic effects on hMSCs, a cell population particularly important for bone formation. In the absence of any clinical evidence suggesting that "more vancomycin is better," and our data suggesting that more vancomycin is harmful in vitro, surgeons electing to use topical vancomycin in spine surgery should restrict their use to the doses currently reported in the available published studies unless specific reasons exist otherwise. This study does not establish a contraindication to the use of topical vancomycin, nor does it suggest that pseudarthroses are attributable to vancomycin use.
局部应用万古霉素在脊柱手术中的使用越来越普遍。大型回顾性研究表明,局部应用万古霉素能有效降低术后感染的成本。目前,对于局部可应用的最大剂量知之甚少。当1克万古霉素混入骨移植材料中,另外1克自由涂抹于脊柱伤口时,术后即刻抗生素的局部浓度范围为260 - 2900μg/mL,术后第二天为50 - 730μg/mL。我们推测,大剂量的万古霉素可能对间充质干细胞(MSCs)有毒性。
从接受常规择期全髋关节置换术患者的股骨髓腔中获取骨髓。采用塑料贴壁法分离间充质干细胞。将细胞暴露于不同剂量的万古霉素中24小时,然后评估细胞活力。用茜素红染色评估成骨潜能。
使用万古霉素后出现剂量依赖性细胞死亡。与不含万古霉素的对照组相比,万古霉素浓度为400μg/mL时,间充质干细胞死亡率为9.43%(p = 0.047);1600μg/mL时为13.79%(p = 0.0047);3200μg/mL时为19.35%(p < 0.0001);6400μg/mL时为24.82%(p <