Locally delivered antistaphylococcal lysin exebacase or CF-296 is active in methicillin-resistant Staphylococcus aureus implant-associated osteomyelitis

Introduction: Staphylococcus aureus is the most common cause of orthopedic infections and can be challenging to treat, especially in the presence of a foreign body. The antistaphylococcal lysins exebacase and CF-296 have rapid bactericidal activity, a low propensity for resistance development, and synergize with some antibiotics. Methods: Rabbit implant-associated osteomyelitis was induced by drilling into the medial tibia followed by locally delivering exebacase, CF-296, or lysin carrier. A titanium screw colonized with methicillin-resistant S. aureus (MRSA) IDRL-6169 was inserted. Intravenous daptomycin or saline was administered and continued daily for 4 d. On day 5, rabbits were euthanized, and the tibiae and implants were collected for culture. Results were reported as log ${}_{10}$ colony forming units (cfu) per gram of bone or log ${}_{10}$ cfu per implant, and comparisons among the six groups were performed using the Wilcoxon rank sum test. Results: Based on implant and bone cultures, all treatments resulted in significantly lower bacterial counts than those of controls ( $P\le 0.0025$ ). Exebacase alone or with daptomycin as well as CF-296 with daptomycin were more active than daptomycin alone ( $P\le 0.0098$ ) or CF-296 alone ( $P\le 0.0154$ ) based on implant cultures. CF-296 with daptomycin was more active than either CF-296 alone ( $P=0.0040$ ) or daptomycin alone ( $P=0.0098$ ) based on bone cultures. Conclusion: Local delivery of either exebacase or CF-296 offers a promising complement to conventional antibiotics in implant-associated infections.