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Published on: June 23, 2020
Activity of Phage and Vancomycin in a Murine Staphylococcus aureus Periprosthetic Joint Infection Model Managed With
Sebastian C Herren1, Melissa J Karau1, Sergio F Guarin Perez2
1Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract:
Periprosthetic joint infection (PJI) is a serious complication of total joint arthroplasty (TJA), with Staphylococcus aureus being one of the most common causative organisms. Irrigation and debridement with component retention (IDCR) is often performed to manage PJI. Antimicrobial treatment that targets S. aureus biofilms on prosthesis surfaces and within bone may be especially helpful when retaining a prosthesis. Phages, viruses that specifically infect bacteria, are a potential therapeutic consideration. Using a biofilm time kill assay in bovine synovial fluid, bactericidal activity of vancomycin or phage K (32 µg/mL and 1011 pfu/mL, respectively) as well as the combination of phage K (1010 pfu/mL) and vancomycin (32 µg/mL) was observed against a methicillin-resistant S. aureus (MRSA) strain. Using a murine PJI model, mice infected with MRSA underwent IDCR followed by phage administration into the joint space with or without systemically administered vancomycin. Mice receiving both phage and vancomycin had significant reductions in MRSA on the prosthesis surface compared to untreated or vancomycin-treated mice. Phage K showed bactericidal activity in vitro and was active when locally delivered in combination with systemically administered vancomycin in a murine PJI model managed with IDCR.
Insights
Bacteriophage K combined with vancomycin effectively reduced Staphylococcus aureus in a mouse model of periprosthetic joint infection (PJI) after irrigation and debridement. This combination therapy shows promise for treating PJI.
Area of Science:
- Orthopedic Surgery
- Infectious Diseases
- Microbiology
- Biotechnology
Background:
- Periprosthetic joint infection (PJI) is a severe complication following total joint arthroplasty (TJA).
- Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is a common pathogen in PJI.
- Effective antimicrobial strategies are crucial for managing PJI, especially when retaining prosthetic components.
Purpose of the Study:
- To evaluate the efficacy of bacteriophage K, alone and in combination with vancomycin, against MRSA biofilms in vitro.
- To assess the therapeutic potential of locally delivered bacteriophage K with or without systemic vancomycin in a murine model of PJI managed with irrigation and debridement with component retention (IDCR).
Main Methods:
- In vitro biofilm time kill assays were performed using bovine synovial fluid.
- A murine PJI model was established using MRSA.
- Mice underwent IDCR followed by intra-articular phage administration, with or without systemic vancomycin.
Main Results:
- Phage K demonstrated bactericidal activity against MRSA biofilms in vitro, both alone and in combination with vancomycin.
- In the murine model, combined intra-articular phage K and systemic vancomycin significantly reduced MRSA on prosthesis surfaces compared to untreated or vancomycin-only groups.
- Local phage delivery combined with systemic vancomycin was effective in a murine PJI model managed with IDCR.
Conclusions:
- Bacteriophage K exhibits in vitro bactericidal activity against MRSA biofilms.
- Local delivery of bacteriophage K in combination with systemic vancomycin is a promising therapeutic strategy for managing MRSA PJI after IDCR.
- This combination therapy warrants further investigation for clinical application in PJI treatment.
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