Attacking MRSA With a New Immunotherapy Model

How can methicillin‐resistant Staphylococcus aureus (MRSA) be avoided after revision surgery in orthopedics?

This is a substantial problem that researchers were addressing in their recent study, “Immunotherapy synergizes with debridement and antibiotic therapy in a murine 1‐stage exchange model of MRSA implant‐associated osteomyelitis.” This study appears in the February 5, 2018 edition of The Journal of Orthopaedic Research.

Co-author, Edward Schwarz, Ph.D., Center for Musculoskeletal Research and Department of Orthopedics, University of Rochester Medical Center in New York, told OTW, “MRSA infected total joint replacements currently have a very high rate of reinfection. In order to develop an adjuvant therapy to combat MRSA infections, we needed to develop a valid small animal model of a 1-stage revision surgery.”

“Our model involves establishing quantifiable implant-associated osteomyelitis (bone infection), as well as longitudinal, radiographic, bacteriologic and histologic outcomes of complete implant exchange surgery. We are also evaluating our experimental anti-Gmd passive immunization as an adjuvant therapy to standard of care revision surgery and vancomycin therapy for MRSA implant-associated osteomyelitis.”

According to the authors, “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:

• no infection control;
• infected placebo;
• anti‐Gmd;
• vancomycin;
• and 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‐revision), and efficacy was assessed via colony forming units (CFU) on explanted hardware, micro‐CT, and histology.”

“It appears our animal model is, in fact, valid and includes all of the necessary outcome measures. Our results also show the initial proof of concept that our anti-Gmd immunotherapy interacts synergistically with standard of care vancomycin therapy through a distinct mechanism of action to reduce MRSA.”

“Anti-Gmd passive immunotherapy is feasible for the treatment of S. aureus implant-associated osteomyelitis. Our preclinical studies warrant further investigation. Checkpoint inhibitors are proving to be a panacea for cancer immunotherapy (i.e., Keytruda). Similar thinking and research could lead to effective immunotherapies for osteomyelitis.”