Vancomycin Derivative Photopolymerized to Titanium Kills S. epidermidis

Abstract

Infections in the setting of orthopaedic hardware remain a serious complication. Traditional treatment modalities rely on antibiotic-loaded biomaterials and/or prolonged intravenous therapy, both of which suffer major limitations. We hypothesized a derivatized form of the glycopeptide antibiotic vancomycin could be covalently attached to a Ti-6Al-4V implant alloy to form a bactericidal surface capable of killing bacteria relevant to orthopaedic infections. First, a polymerizable poly(ethylene glycol)-acrylate derivative of vancomycin was synthesized. This monomer was characterized by liquid chromatography, 1H NMR spectroscopy, and MIC and MBC determination. The monomer was subsequently photochemically polymerized to implant grade Ti-6Al-4V alloy. The coating was bactericidal against Staphylococcus epidermidis through initial release of unattached antibiotic species followed by continued surface-contact-mediated bacterial killing by covalently tethered vancomycin. Through this surface-contact mechanism, the number of colony forming units dropped by ca. fivefold from an initial inoculum of 1 x 10(6) cfu/mL over 4 hours and by ca. 100-fold with respect to nonbactericidal control surfaces. An inoculum of 1 x 10(4) cfu/mL was reduced to undetectable levels over 17 hours. This coating method allows a loading dose several thousand times larger than that achieved with monolayer vancomycin coupling approaches and holds promise for the treatment of orthopaedic infections.