title: Vancomycin covalently bonded to titanium alloy prevents bacterial colonization.
abstract: Periprosthetic infection is a devastating consequence of implant insertion and can arise from hematogenous sources or surgical contamination. Microbes can preferentially colonize the implant surface and, by forming a biofilm, escape immune surveillance. We hypothesized that if an antibiotic can be tethered to a titanium alloy (Ti) surface, it will inhibit bacterial colonization, prevent biofilm formation, and avert late-stage infection. To test this hypothesis, a Ti rod was covalently derivatized with vancomycin. Reaction efficiencies were evaluated by colorimetric and spectrophotometric measurements. The vancomycin-modified surface was stable in aqueous solutions over extended time periods and maintained antibiotic coverage, even after press-fit insertion into a cadaverous rat femora. When evaluated using fluorescently labeled bacteria, or by direct colony counts, the surface-bound antibiotic prevented bacterial colonization in vitro after: (1) exposure to high levels of S. aureus; (2) extended incubation in physiological buffers; and (3) repeated bacterial challenges. Importantly, whereas the vancomycin-derivitized pins prevented bacterial colonization, S. aureus adhered to control pins, even in the presence of concentrations of vancomycin that exceeded the strain MIC. These results demonstrate that we have effectively engineered a stable, bactericidal Ti surface. This new surface holds great promise in terms of mitigating or preventing periprosthetic infection.
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University, 1015 Walnut Street, Suite 501, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Valentin
authors.initials: V
authors.lastname: Antoci
authors.forename: Samuel B
authors.initials: SB
authors.lastname: King
authors.forename: Binoy
authors.initials: B
authors.lastname: Jose
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
authors.forename: Allen R
authors.initials: AR
authors.lastname: Zeiger
authors.forename: Eric
authors.initials: E
authors.lastname: Wickstrom
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Freeman
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Composto
authors.forename: Paul
authors.initials: P
authors.lastname: Ducheyne
authors.forename: Irving M
authors.initials: IM
authors.lastname: Shapiro
authors.forename: Noreen J
authors.initials: NJ
authors.lastname: Hickok
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Adams
mesh_terms: D000497:Alloys / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D019736:Prostheses and Implants / Q000382:microbiology*; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects; D014025:Titanium / Q000737:chemistry*; D014640:Vancomycin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000497:Alloys; D000900:Anti-Bacterial Agents; D014640:Vancomycin; D014025:Titanium