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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.