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, H 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 × 10 cfu/mL over 4 hours and by ca. 100-fold with respect to nonbactericidal control surfaces. An inoculum of 1 × 10 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. © 2007 Lippincott Williams & Wilkins, Inc.