Abstract
Introduction
Surgical site infections represent a major complication of spinal surgery. The application of lyophilized vancomycin into the wound is reported to significantly decrease infection rates. As concentrations applied locally can exceed the minimal bacterial inhibitory concentration for more than a 1000-fold, toxic side effects on local tissue may be possible.
Materials and Methods
Primary osteoblast cell cultures were generated from bone tissue samples of 10 patients. Samples were incubated in absence or presence of 3, 6, or 12 mg/cm2 vancomycin according to a planned phase I clinical trial protocol. Changes in pH, osteoblast migration, proliferation, and viability were analyzed. Alkaline phosphatase and mineralization patterns were studied.
Results
The application of more than 3 mg/cm2 vancomycin induced a decline of pH toward the acidic range. The migration potential of osteoblasts was decreased from 100% (control samples) to zero (12 mg/cm2 vancomycin) in a dose-dependent manner. Cell proliferation was significantly inhibited at dosages above 3 mg/cm2. Significant cell death was observed if the dosage applied exceeded 6 mg/cm2. The synthesis of alkaline phosphatase was markedly reduced in all dosages applied and calcium deposition was significantly decreased in dosages above 3 mg/cm2.
Conclusion
As bone remodeling requires the immigration, proliferation, and differentiation of osteoblasts at the fusion site, high dosages of intrawound vancomycin might interfere with regenerative processes and increase the risk of nonunion. To allow an appropriate balance of infection risk and the risk of nonunion, the minimal local concentration required should be determined by controlled in vivo studies.