Polymer-controlled extended combination release of silver and chlorhexidine from a bone void filler

Although rates of total joint prosthetic infections remain relatively constant at 1-3%, an increasing number of orthopedic procedures and a corresponding rise in the absolute number of infectious complications mandate distinctly new solutions. In order to combat the implant infection threat, an antibiotic-releasing bone void filler (BVF), commercial tradename, ElutiBone™, has been developed using a combination of commercially available ceramic-based BVF plus clinically familiar biocompatible polymers, and a variety of select, dispersed antibiotics. While several traditional antibiotics have been successfully released for an extended duration, a more versatile strategy, releasing multiple antibiotics simultaneously, may be possible. In this study, the antiseptic chlorhexidine and a variety of bacteriostatic silver compounds were incorporated to provide synergistic antimicrobial activity upon release in combination formulations from ElutiBone matrices. Silver chloride was the most effective bacteriostatic tested (p=0.05), showing a measurable zone of inhibition at spiked concentrations as low as 31µg/ml. Subsequently, silver chloride was used in combination with the antiseptic chlorhexidine to test for enhanced antimicrobial bioactivity against S. aureus. Measurable synergy between the two compounds confirmed the suitability of ElutiBone™ to locally deliver this multidrug antimicrobial cocktail. A myriad of other drug interactions could and should be tested in this novel system in order to expand the utility and combat the increasing prevalence of polymicrobial infections.