Bacteriophage therapy as an innovative strategy for the treatment of Periprosthetic Joint Infection: a systematic review

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.

Keywords: Bacteriophage; Hip arthroplasty; Knee arthroplasty; Periprosthetic joint infection.

Fig. 1

Flowchart showing the results of the search and the methodology selected

Fig. 2

A schematic representation of the application of phage therapy techniques for PJI in the knee, the specific steps as follows: a: Isolate the patient’s pathogenic bacteria and cultivate them in vitro; b: Perform bacterial typing and screen for susceptible lytic bacteriophages; c: Amplify and remove endotoxins from the bacteriophages, and prepare qualified single or cocktail bacteriophage formulations according to Good Manufacturing Practice (GMP) standards; d: Select an appropriate treatment regimen based on the patient’s tolerance. The included studies reported methods such as intra-articular injection, drainage tube irrigation, local application with hydrogel and bone cement carriers, as well as systemic administration via oral or intravenous routes; e: Combine with antibiotic therapy

Fig. 3

A schematic representation of the lytic cycle and lysogenic life cycle and the general processes of bacteriophages. Although the lysogenic cycle of temperate bacteriophages does not immediately cause bacterial lysis, it can induce genetic remodeling and, under suitable conditions, may transition into the lytic cycle, leading to bacterial destruction and replication of the bacteriophage. And the lytic cycle of virulent bacteriophages produces lysins that degrade the bacterial cell wall, rapidly leading to facilitates dissemination of themselves