Bacteriophage therapy as an innovative strategy for the treatment of Periprosthetic Joint Infection: a systematic review
Authors: Yang Shengdong , Mukh Assala Abu , Abdelatif Elsayed , Schmidt Axel , Batailler Cécile , Ferry Tristan , Lustig Sébastien 
Published: September 2024

Abstract
Background
Periprosthetic Joint Infection (PJI) following hip and knee arthroplasty is a catastrophic complication in orthopaedic surgery. It has long been a key focus for orthopaedic surgeons in terms of prevention and management. With the increasing incidence of antibiotic resistance in recent years, finding more targeted treatment methods has become an increasingly urgent issue. Bacteriophage Therapy (BT) has emerged as a promising adjunctive treatment for bone and joint infections in recent years. It not only effectively kills bacteria but also demonstrates significant anti-biofilm activity, garnering substantial clinical interest due to its demonstrated efficacy and relatively low incidence of adverse effects.

Purpose
This review aims to systematically evaluate the efficacy and safety of bacteriophage therapy in treating PJI following hip and knee arthroplasty, providing additional reference for its future clinical application.

Methods
Following predefined inclusion and exclusion criteria, our team conducted a systematic literature search across seven databases (PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, CNKI, and WanFang Database). The search was conducted up to May 2024 and included multiple clinical studies on the use of bacteriophage therapy for treating PJI after hip and knee arthroplasty to assess its efficacy and safety.

Results
This systematic review included 16 clinical studies after screening, consisting of 15 case reports and one prospective controlled clinical trial, involving a total of 42 patients with PJI treated with bacteriophage therapy. The average patient age was 62.86 years, and 43 joints were treated, with patients undergoing an average of 5.25 surgeries. The most common pathogen in these infections was Staphylococcus aureus, accounting for 18 cases. 33 patients received cocktail therapy, while nine were treated with a single bacteriophage preparation. Additionally, all patients underwent suppressive antibiotic therapy (SAT) postoperatively. All patients were followed up for an average of 13.55 months. There were two cases of recurrence, one of which resulted in amputation one year postoperatively. The remaining patients showed good recovery outcomes. Overall, the results from the included studies indicate that bacteriophage therapy effectively eradicates infectious strains in various cases of PJI, with minimal side effects, demonstrating promising clinical efficacy.

Conclusion
In the treatment of PJI following hip and knee arthroplasty, bacteriophages, whether used alone or in combination as cocktail therapy, have shown therapeutic potential. However, thorough preoperative evaluation is essential, and appropriate bacteriophage types and treatment regimens must be selected based on bacteriological evidence. Future large-scale, randomized controlled, and prospective trials are necessary to validate the efficacy and safety of this therapy.