Vancomycin Bonded to Bone Grafts Prevents Bacterial Colonization

Abstract

Infection is an important medical problem associated with the use of bone allografts. To retard bacterial colonization, we have recently reported on the modification of bone allografts with the antibiotic vancomycin (VAN). In this report, we examine the ability of this antibiotic-modified allograft to resist bacterial colonization and biofilm formation. When antibiotic was coupled to the allograft, a uniform distribution of the antibiotic was apparent. Following challenges with Staphylococcus aureus for 6 h, the covalently bonded VAN decreased colonization as a function of inoculum, ranging from 0.8 to 2.0 log 10 CFU. Furthermore, the VAN-modified surface resisted biofilm formation, even in topographical niches that provide a protected environment for bacterial adhesion. Attachment of the antibiotic to the allograft surface was robust, and the bonded VAN was stable whether incubated in aqueous media or in air, maintaining levels of 75 to 100% of initial levels over 60 days. While the VAN-modified allograft inhibited the Gram-positive S. aureus colonization, in keeping with VANs spectrum of activity, the VAN-modified allograft was readily colonized by the Gram-negative Escherichia coli. Finally, initial toxicity measures indicated that the VAN-modified allograft did not influence osteoblast colonization or viability. Since the covalently tethered antibiotic is stable, is active, retains its specificity, and does not exhibit toxicity, it is concluded that this modified allograft holds great promise for decreasing bone graft-associated infections.

Effect of Coadministration of Vancomycin and BMP-2 on Cocultured Staphylococcus aureus and W-20-17 Mouse Bone Marrow Stromal Cells In Vitro

“…One suggested approach to combating this issue is to use a specialized synthetic bone graft material capable of delivering both antibiotics and growth factors locally after implantation (9,16,25,31,46,47,50). While antibiotic integration into bone grafts has been proven successful, less work has been done to deliver an antibiotic and a growth factor together (either in series or parallel) (24,25).…”

“…While antibiotic integration into bone grafts has been proven successful, less work has been done to deliver an antibiotic and a growth factor together (either in series or parallel) (24,25). As a result of limiting the need for the antibiotic to travel systemically, there are higher antibiotic levels at the site of the wound and systemically safe levels, thus paving the way for resident osteoblasts to penetrate into the graft well before the offending bacteria are able to reach high confluence and form biofilms (38).…”

Novel Antibiotic-loaded Point-of-care Implant Coating Inhibits Biofilm

“…Antibiotics released from coatings were confirmed to be active in inhibiting growth of microorganisms through turbidity and zone of inhibition assays with similar activity to other antimicrobial coatings [5,14,25,43,69]. Although effective in inhibiting bacterial growth and biofilm formation, several of the implant coating strategies have the limitation of requiring prefabrication [25,43] and chemical modification with specific preselected antibiotics [4,29]. Release of antibiotic resembles the burst release observed in commonly used polymethylmethacrylate (PMMA) and calcium sulfate drug delivery matrices [23,47].…”

“…Localized antimicrobial drug delivery systems, including biomaterial carrier matrices and coatings on implants, have become a focus to combat biofilm formation and infection for both preventive and treatment strategies [1,7,13,27,29,43,49,63,64]. We provide the initial description of a novel lipid-based material we have developed to serve as a carrier matrix for antibiotics that can be applied to an implant with clinician-selected antibiotics at the point of care.…”

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“…compared to other antibiotics 2,3 . It should be administered intravenously over a minimum of 60 minutes to avoid infusion-related reactions for a period reaching 6 weeks or longer 4 .…”