Bacteriophage therapy in musculoskeletal infections: a systematic review

Abstract Background Bone and joint infections are a therapeutic dilemma for healthcare providers in all fields. Musculoskeletal infections, particularly those associated with implants or chronic osteomyelitis, continue to pose a therapeutic challenge. Treatment failures remain common, especially in the context of multidrug-resistant organisms or biofilm-mediated persistence. Given these challenges, bacteriophage therapy (BT) has emerged as a promising adjunctive or salvage modality. This systematic review aims to critically evaluate the current clinical evidence regarding the application, outcomes, and safety profile of BT in the management of complex bacterial musculoskeletal infections. Methods This systematic review was conducted in accordance with the 2020 PRISMA statement. PubMed, Google Scholar, Embase, and Web of Science were accessed in July 2025. No time constraints were used for the search. All clinical studies investigating BT for bacterial musculoskeletal infections were considered for eligibility. The methodological quality of the included studies was assessed using the Cochrane ROBINS-I tool for non-randomised studies and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for case reports and case series. Results Twenty-seven clinical studies were included, comprising a total of 105 patients. The mean age was 58.9 ± 22.4 years, and 23.8% (25/105) were women. The overall complication rate was 18.1% (19/105). A change in the dominant infecting pathogen during treatment was observed in 2.9% of cases (3/105). Across the included reports, most patients achieved clinical improvement with infection control and, where applicable, implant retention following adjunctive bacteriophage therapy. Conclusions Bacteriophage therapy may represent a promising adjunctive option for selected cases of musculoskeletal infections that are unresponsive to standard treatments. Nevertheless, the current evidence remains extremely limited and heterogeneous, being based almost exclusively on case reports and small case series. At present, bacteriophage therapy should be regarded as experimental, and its clinical role cannot be defined without high-quality prospective and randomised studies.