Activity of Phage and Vancomycin in a Murine Staphylococcus aureus Periprosthetic Joint Infection Model Managed With Debridement and Implant Retention.

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.