Abstract
With the increase in the placement of prosthetic joints and other hardware in the body, associated infections have risen. These infections are complicated to treat due to the underlying bacteria generating matrices that resist clearance by immune system effectors or antibiotics. These matrices, biofilms, have two primary ways of being eradicated: either by physical removal during surgery or by killing the underlying bacteria, usually with antibiotics. The viruses that kill bacteria, bacteriophages, are readily capable of entering biofilms and eradicating the bacteria therein. Therefore, bacteriophages have therapeutic potential as a supplement to antibiotics for the treatment of prosthetic joint infections. In this investigation, we generate a mathematical and computer-simulation model to explore the contributions of the innate immune system with antibiotics, bacteriophage, and the joint action to control biofilm-associated infections. Our results question the proposition that bacteriophages are an effective addition in the treatment of prosthetic joint infections.
Data availability
The Berkeley Madonna programs used for these simulations are available at EcLF.net. All data are presented in this article or its supplementary materials.
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Acknowledgements
We thank the other members of the Levin Lab for their comments on an earlier version of this manuscript. BRL would like to thank the U.S. National Institute of General Medical Sciences for their funding support via R35GM136407 and the Emory University Antibiotic Resistance Center. The funding sources had no role in the design of this study and will not have any role during its execution, analysis, interpretation of the data, or drafting of this report. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Conceptualization: B.R.L., T.G.G., B.A.B., M.H.W. Methodology: B.R.L., T.G.G., B.A.B. Investigation: B.R.L., T.G.G., B.A.B. Visualization: B.R.L., T.G.G., B.A.B. Funding acquisition: B.R.L. Project administration: B.R.L., T.G.G., B.A.B., M.H.W. Supervision: B.R.L., T.G.G., B.A.B., M.H.W. Writing—initial draft: B.R.L., T.G.G., B.A.B., M.H.W. Writing—review & editing: B.R.L., T.G.G., B.A.B., M.H.W.
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Levin, B.R., Gil-Gil, T., Berryhill, B.A. et al. A theoretical exploration of protocols for treating prosthetic joint infections with combinations of antibiotics and bacteriophage. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-025-00908-2
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DOI: https://doi.org/10.1038/s41522-025-00908-2
