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Toward the development of immunotherapy with anti\u2010glucosaminidase monoclonal antibodies (anti\u2010Gmd), we aimed to: (i) develop a murine 1\u2010stage exchange model of bioluminescent MRSA (USA300LAC::lux) contaminated femoral implants; and (ii) utilize this model to demonstrate the synergistic effects of combination vancomycin and anti\u2010Gmd therapy on reinfection and bone healing. Following an infection surgery, the original plate and two screws were removed on day 7, and exchanged with sterile implants. Mice were randomized to five groups: (i) no infection control; (ii) infected placebo; (iii) anti\u2010Gmd; (iv) vancomycin; and (v) combination therapy. Bioluminescent imaging (BLI) was performed on days 0, 1, 3, 5, 7, 8, 10, 12, and 14. Mice were euthanized on day 14 (day 7 post\u2010revision), and efficacy was assessed via colony forming units (CFU) on explanted hardware, micro\u2010CT, and histology. As monotherapies, anti\u2010Gmd inhibited <jats:italic>Staphylococcus<\/jats:italic> abscess communities, and vancomycin reduced CFU on the implants. However, only combination therapy prevented increased BLI post\u2010revision surgery, with a significant 6.5\u2010fold reduction on day 10 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. placebo), and achieved sterile implant levels by day 12. Synergistic effects were also apparent from reduced osteolysis and increased new bone formation around the screws only observed following combination therapy. Taken together, we find that: (i) this murine femoral plate 1\u2010stage revision model can efficiently evaluate therapies to prevent reinfection; and (ii) immunotherapy plays a distinct role from antibiotics to reduce reinfection following revision surgery, such that synergy to achieve osseointegration is possible. \u00a9 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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