title: Does intrawound application of vancomycin influence bone healing in spinal surgery?
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Spine Surgery, Spine Center, Orthopaedic Hospital Speising, Speisinger Str. 109, 1130, Vienna, Austria. Claudia.Eder@oss.at.
authors.forename: Claudia
authors.initials: C
authors.lastname: Eder
authors.affiliation: Department of Spine Surgery, Spine Center, Orthopaedic Hospital Speising, Speisinger Str. 109, 1130, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schenk
authors.affiliation: Department of Spine Surgery, Spine Center, Orthopaedic Hospital Speising, Speisinger Str. 109, 1130, Vienna, Austria.
authors.forename: Jana
authors.initials: J
authors.lastname: Trifinopoulos
authors.affiliation: University of Applied Sciences, Vienna, Austria.
authors.forename: Büsra
authors.initials: B
authors.lastname: Külekci
authors.affiliation: Karl Franzens University Graz, Graz, Styria, Austria.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kienzl
authors.affiliation: Department of Spine Surgery, Spine Center, Orthopaedic Hospital Speising, Speisinger Str. 109, 1130, Vienna, Austria.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schildböck
authors.affiliation: Department of Spine Surgery, Spine Center, Orthopaedic Hospital Speising, Speisinger Str. 109, 1130, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Ogon
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D054443:Cell Migration Assays; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005599:Fractures, Ununited / Q000503:physiopathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D019635:Neurosurgical Procedures; D010006:Osteoblasts / Q000502:physiology; D013122:Spinal Diseases / Q000601:surgery*; D013530:Surgical Wound Infection / Q000188:drug therapy*; D014640:Vancomycin / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Cell migration; Cell proliferation; Cell viability; Intrawound vancomycin; Non-union; Osteoblasts; pH