Abstract
BackgroundMusculoskeletal infections remain a major complication in orthopedic surgery. The local delivery of antibiotics provides the high levels required to treat an infection without systemic toxicity. However, the local toxicity of antibiotic carriers to the mesenchymal stem cells, as a result of both the peak concentrations and the type of carrier, may be significant.MethodsTo address this concern, the elution kinetics of vancomycin and gentamicin from several commercially available antibiotic carriers and several carriers impregnated by a surgeon (10 ml of each sterile carrier were manually mixed with a 500 mg vancomycin and an 80 mg gentamicin solution, and the duration of impregnation was 30 min) were assessed. Moreover, the effects of these antibiotic carriers on stem cell proliferation were investigated. The following two types of stem cells were used: bone marrow and dental pulp stem cells.ResultsThe high eluted initial concentrations from antibiotic impregnated cancellous allogeneic bone grafts (which may be increased with the addition of fibrin glue) did not adversely affect stem cell proliferation. Moreover, an increased dental pulp stem cell proliferation rate in the presence of antibiotics was identified. In contrast to allogeneic bone grafts, a significant amount of antibiotics remained in the cement. Despite the favorable elution kinetics, the calcium carriers, bovine collagen carrier and freeze-dried bone exhibited decreased stem cell proliferation activity even in lower antibiotic concentrations compared with an allogeneic graft.ConclusionsThis study demonstrated the benefits of antibiotic impregnated cancellous allogeneic bone grafts versus other carriers.
Highlights
Musculoskeletal infections remain a major complication in orthopedic surgery
In vitro assessment of antibiotic elution kinetics The elution kinetics of the antibiotics from the carriers are presented in box plots (Figs. 1 and 2)
Herafill® beads G This resorbable gentamicin carrier exhibited significantly different elution kinetics until the seventh day compared with the bone cement (α < 0.05)
Summary
The local delivery of antibiotics provides the high levels required to treat an infection without systemic toxicity. The local toxicity of antibiotic carriers to the mesenchymal stem cells, as a result of both the peak concentrations and the type of carrier, may be significant. Released antibiotics must reach concentration levels above the minimal bactericidal concentration to prevent bacterial resistance; the peak concentration must not affect bone healing. Various types of mesenchymal stem cells may differentially respond to antibiotic impregnated carriers. Previous studies have predominately investigated aminoglycosides and glycopeptides in local antibiotic carriers because of their good pharmacokinetic properties and susceptibility to causative pathogens in implant surgery [4, 5]. Gentamicin alone was effective in 64.2% compared with 89.8% for vancomycin, whereas the combination of vancomycin and gentamicin in 96.4% of causative pathogens delayed periprosthetic infections
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