RESUMO
PURPOSE: Surgical site infections represent a major complication of spinal surgery. The application of lyophilised 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. METHODS: Primary osteoblast cell cultures were generated from bone tissue samples of 10 patients. Samples were incubated in absence or presence of either 3, 6 or 12 mg/cm(2) vancomycin according to a planned phase I clinical trial protocol. Changes in pH, osteoblast migration, proliferation and viability were analysed. Alkaline phosphatase as well as mineralisation patterns was studied. RESULTS: The application of more than 3 mg/cm(2) vancomycin induced a decline of pH. The migration potential of osteoblasts was decreased from 100% (control samples) to zero (12 mg/cm(2) vancomycin) in a dose-dependant manner. Cell proliferation was significantly inhibited at dosages above 3 mg/cm(2). Significant cell death was observed if the dosage applied exceeded 6 mg/cm(2). The synthesis of alkaline phosphatase was markedly reduced in all dosages applied and calcium deposition was significantly decreased in dosages above 3 mg/cm(2). CONCLUSION: As bone remodelling 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 non-union. To allow an appropriate balance of infection risk and the risk of non-union, the minimal local concentration required should be determined by controlled in vivo studies.