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

Abstract

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 4d. On day 5, rabbits were euthanized, and the tibiae and implants were collected for culture. Results were reported as log10 colony forming units (cfu) per gram of bone or log10cfu 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≤0.0025). Exebacase alone or with daptomycin as well as CF-296 with daptomycin were more active than daptomycin alone (P≤0.0098) or CF-296 alone (P≤0.0154) based on implant cultures. CF-296 with daptomycin was more active than either CF-296 alone (PCombining double low line0.0040) or daptomycin alone (PCombining double low line0.0098) based on bone cultures. Conclusion: Local delivery of either exebacase or CF-296 offers a promising complement to conventional antibiotics in implant-associated infections.