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Background Context: Infections remain a leading complication associated with spinal arthrodesis, regardless of the use of prophylactic antibiotics and improved surgical techniques, with incidence of infection as high as 8.2%. Infection prolongs antibiotic usage, increases hospital time, and inevitably inflates overall treatment costs. Local antibiotics, such as vancomycin, have been used in combination with fusion materials over the past decade to decrease infection risk. An ideal graft material would serve a dual role: encouraging vertebral fusion while reducing the incidence of infection., Purpose: The objective of this study was to thoroughly evaluate the use of a vancomycin-loaded demineralized bone matrix (vDBM) for fusion capability while reducing the incidence of surgical site infection., Study Design: Antimicrobial efficacy and spinal fusion were evaluated using a preclinical rabbit model of posterolateral fusion., Materials and Methods: Vancomycin-loaded demineralized bone matrix was prepared and evaluated for in vitro release kinetics and bacterial inhibition. In vivo antibacterial efficacy and fusion capability were performed using a model of posterolateral fusion in a rabbit. First, 10 New Zealand white rabbits underwent a bilateral posterolateral fusion procedure, were inoculated with Staphylococcus aureus, and were treated with either demineralized bone matrix (DBM) or vDBM. Fourteen days after the procedure, the animals were anesthetized and euthanized, and the transverse process was harvested and enumerated for bacterial quantification. Concurrently, 21 New Zealand white rabbits underwent the same procedure and were euthanized 8 weeks after surgery and were evaluated for fusion by manual palpation and radiographic scoring. In addition, two groups of six animals received the DBM or vDBM material as described, but the graft was combined with equal volumes of milled harvest iliac crest bone graft (ICBG). Eight weeks after surgery, these animals were euthanized and also evaluated for fusion by manual palpation and radiographic scoring., Results: Vancomycin continued to be released from the vDBM over the course of 6 days while maintaining sufficient eluate concentrations to maintain a zone of inhibition similar or larger than a vancomycin control. In vivo, vDBM significantly reduced the amount of bacteria within the fusion site compared with DBM, with a 4-log decrease in bacterial bioburden. The use of vDBM, however,showed a decrease in the fusion rate compared with DBM when used in a sterile wound. In a S. aureus-contaminated wound, both the DBM and the vDBM showed decreased fusion rates.Considering DBM materials were most commonly used as autograft extenders, additional animals received either DBM plus ICBG in a sterile wound or vDBM plus ICBG in a contaminated wound. Both groups had similar fusion rates and similar fusion volumes after 8 weeks in vivo., Conclusions: Whereas vDBM reduced the overall bioburden within a contaminated surgical site of posterolateral fusion, the addition of the vancomycin to the DBM reduced the fusion capability of the DBM graft. The addition of ICBG to vDBM restored the fusion capability of the graft while reducing the overall infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Open fractures are often complicated by infection. In cases of severe soft tissue and vascular injury, systemic antibiotics may be ineffective due to their inability to reach and provide direct antimicrobial activity to the zone of injury. High antibiotic concentrations within the wound can be achieved with reduced systemic toxicity by using local antibiotic delivery. As bacteria associated with musculoskeletal injuries frequently form biofilms, antibiotic selection is important. Herein, the use of rifampin, an antibiotic with activity against biofilms, delivered via polymethylmethacrylate (PMMA) beads is evaluated for use in a traumatic musculoskeletal wound model., Methods: PMMA beads loaded with rifampin, or combinations of rifampin and vancomycin, were prepared and evaluated for time to curing, drug release kinetics in vitro, and infection prevention in vivo using a well-established rat model of musculoskeletal infection. A segmental bone defect was created and contaminated with methicillin susceptible Staphylococcus aureus (UAMS-1). Wounds were debrided, irrigated, and treated with PMMA beads, containing rifampin or combinations of rifampin plus vancomycin, following a 6-h (early) or 24-h (delayed) treatment. After 14days, tissue, implants, and beads were removed for bacterial quantification and assessed for rifampin resistance., Results: There was a direct association between loaded concentration and release kinetics of the rifampin and vancomycin from PMMA beads. Higher rifampin concentrations delayed PMMA curing times. The addition of vancomycin to PMMA resulted in more rapid release of rifampin from beads. However, the highest concentration of rifampin loaded PMMA beads (10% wt/wt) was the only treatment to significantly reduce bacterial counts. No rifampin resistance was observed., Conclusion: Although higher concentrations of rifampin resulted in significant reductions of bacteria, these levels extended PMMA curing times and transformed PMMA material characteristics. While these characteristics make the material unsuitable for weight-bearing applications, such as total joint arthroplasty, the use of rifampin-loaded PMMA beads may be an effective intervention in a contaminated traumatic extremity wound due to its ability to eradicate biofilms., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the effectiveness of locally applied vancomycin powder at different times postinfection in a contaminated traumatic animal model., Methods: This study used an established segmental defect rat femur model contaminated with Staphylococcus aureus UAMS-1 followed by treatment at 6 or 24 hours postinfection. Three treatments were evaluated: debridement and irrigation alone (control group) or in combination with either vancomycin powder or vancomycin-impregnated poly(methyl methacrylate) beads. Serum vancomycin levels were determined at scheduled time points over 14 days; bone, surrounding muscle, and implants were harvested for bacterial and inflammatory analyses., Results: Locally applied vancomycin powder and impregnated beads significantly reduced bacteria both within the bone and implant when treatment was performed at 6 hours. Delaying treatment to 24 hours significantly reduced the therapeutic efficacy of locally applied vancomycin of both groups. Serum vancomycin levels were detectable in all animals treated with vancomycin powder at 24 hours, but absorption was negligible from beads. At 14 days, vancomycin was detectable in the surrounding musculature of all animals and in serum of 20% of animals treated with vancomycin powder., Conclusions: This study suggests that vancomycin powder is a promising adjunctive therapy for preventing infection in traumatic wounds when treatment is performed early. This time-dependent effectiveness of vancomycin powder is similar to that observed with systemic and other local delivery adjuncts, which is likely attributable to biofilm formation after contamination, conferring intrinsic recalcitrance to antimicrobials.