Self-Protecting Bactericidal Titanium Alloy Surface Formed by Covalent Bonding of Daptomycin Bisphosphonates

Infections are a devastating complication of titanium alloy orthopedic implants. Current therapy includes antibiotic-impregnated bone cement and antibiotic-containing coatings. We hypothesized that daptomycin, a Gram-positive peptide antibiotic, could prevent bacterial colonization on titanium alloy surfaces if covalently bonded via a flexible, hydrophilic spacer. We designed and synthesized a series of daptomycin conjugates for bonding to the surface of 1.0 cm(2) Ti6Al4V foils through bisphosphonate groups, reaching a maximum yield of 180 pmol/cm(2). Daptomycin-bonded foils killed 53 +/- 5% of a high challenge dose of 3 x 10(5) cfu Staphylococcus aureus ATCC 29213.