Deep surgical site infection rates up to 15% have been reported after multilevel spinal surgery [Caroom C et al. Spine (Phila Pa 1976). 2013]. Furthermore, there is an increasing incidence of cephalosporin-resistant bacterial strains [Sweet FA et al. Spine (Phila Pa 1976). 2011]. Interest in intrawound vancomycin powder has grown, with early data suggesting decreased infection rates [Pahys JM et al. J Bone Joint Surg Am. 2013]. In a prior study, however, drainage from wounds treated with vancomycin was found to contain levels of vancomycin high enough to cause toxic effects in the surrounding tissue [Sweet F et al. Spine J. 2009]. Thus, further research is needed in order to determine the vancomycin dose for intrawound application that optimizes bactericidal effects while minimizing detrimental effects on bone healing.

Michael Ogon, MD, PhD, Orthopaedic Hospital Speising, Wien, Austria, reported data from an in vitro study entitled Does Intrawound Application of Vancomycin Influence Bone Regeneration in Spinal Fusion? [Eder C et al. Spine. 2014], indicating that locally applied vancomycin interferes with migration, proliferation, and differentiation of human osteoblasts (particularly at doses of 6 and 12 mg/cm²) and thus may influence bone fusion after spinal surgery.

The protocol for this study was based on a phase 1 US Dose Escalation Trial of Intrasite Vancomycin Pharmacokinetics study [NCT01764750], which was designed to develop rules for standardizing application and dosing, define peak/trough concentrations and clearance parameters, verify bactericidal potency, and select a dose for use in future studies. The study is not yet open for recruitment but expects to enroll 40 adult patients who are undergoing posterior instrumented spinal surgery with an instrumented fusion of ≥ 3 vertebral levels. The primary outcome measures were wound and seroma vancomycin concentrations.

The objectives of this study [Eder C et al. Spine. 2014] were to assess the effect of vancomycin on changes in local pH, cell migration, proliferation, viability, and morphological changes. Prof Ogon presented data based on an analysis of bone samples from 10 patients (5 men and 5 women; mean age 57 years; 2 smokers). Cells were cultured in Dulbecco's modified Eagle's medium plus 10% fetal calf serum plus 2 mM L-glutamine plus 0.05 ascorbic acid plus gentamycin 50 μg/ml plus vancomycin 3, 6, or 12 mg/cm² or no vancomycin.

Local application of vancomycin was associated with a significant decline in pH to a nonphysiologic range at doses of 6 mg/cm² (P < .015) or 12 mg/cm² (P < .001). It also resulted in a dose-dependent suppression of osteoblast migration (control, 100%; 3 mg/cm², 44%; 6 mg/cm², 33%).

After 24 hours, cell proliferation and viability were also reduced, with the reductions being significant at the 6 and 12 mg/cm² doses for proliferation and at the 12 mg/cm² dose for viability (both P < .001). The application of vancomycin also led to a significant (P < .001) inhibition of alkaline phosphatase expression (15.4% in controls vs 1.8% at 3 mg/cm² and undetectable at the 6 and 12 mg/cm² doses).

Dr Ogon concluded that cell migration, proliferation, and differentiation are key factors in osteogenesis. To properly balance the risks of infection and nonunion, controlled in vivo studies should be conducted to establish the minimal local concentrations of vancomycin necessary for infection prevention.