Articles | Volume 7, issue 4
Original full-length article
27 Jul 2022
Original full-length article |  | 27 Jul 2022

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

Melissa Karau, Suzannah Schmidt-Malan, Jay Mandrekar, Dario Lehoux, Raymond Schuch, Cara Cassino, and Robin Patel

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Cited articles

Alder, K. D., Lee, I., Munger, A. M., Kwon, H.-K., Morris, M. T., Cahill, S. V., Back, J., Kristin, E. Y., and Lee, F. Y.: Intracellular Staphylococcus aureus in bone and joint infections: A mechanism of disease recurrence, inflammation, and bone and cartilage destruction, Bone, 141, 115568,, 2020. 
Asempa, T. E., Abdelraouf, K., Carabeo, T., Schuch, R., and Nicolau, D. P.: Synergistic activity of exebacase (CF-301) in addition to daptomycin against Staphylococcus aureus in a neutropenic murine thigh infection model, Antimicrob. Agents Chemother., 64, e02176–02119, 2019. 
Chambers, H. F., Basuino, L., Diep, B., Steenbergen, J., Zhang, S., Tattevin, P., and Alder, J.: Relationship between susceptibility to daptomycin in vitro and activity in vivo in a rabbit model of aortic valve endocarditis, Antimicrob. Agents Chemother., 53, 1463–1467, 2009. Direct lysis of Staph aureus resistant pathogen trial of exebacase (DISRUPT), NCT04160468,, last access: 24 September 2021. 
Cobb, L. H., Park, J., Swanson, E. A., Beard, M. C., McCabe, E. M., Rourke, A. S., Seo, K. S., Olivier, A. K., and Priddy, L. B.: CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection, PLoS One, 14, e0220421,, 2019. 
Short summary
Orthopedic infections are complex, often requiring surgical intervention and prolonged antibiotic therapy, especially in the presence of a foreign body. In a rabbit model of implant-associated methicillin-resistant Staphylococcus aureus osteomyelitis, the lysins exebacase and CF-296 delivered locally with and without systemic daptomycin resulted in lower bacterial counts than those of control animals, showing a promising complement to conventional antibiotics in implant-associated infections.