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The Effects of Topical Vancomycin on Mesenchymal Stem Cells: More May Not Be Better

Stacey Chu, BA,1 Nita Chen, BA,2 Alexis B.C. Dang, MD,3 Alfred C. Kuo, MD, PhD,3 Alan B. C. Dang, MD, 3

1Geisel School of Medicine at Dartmouth College, West Lebanon, NH, 2Albany Medical College, School of Medicine, Albany NY, 3University of California, San Francisco, Department of Orthopaedic Surgery, San Francisco, CA

Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.

Level of Evidence: N/A; In Vitro Controlled Laboratory Study

Page Start: 
85
keywords: 
vancomycin, Infection, Fusion, arthrodesis, Pseudarthrosis
Volume 11 Issue 2
Page End: 
90
doi: 
10.14444/4012