Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus

• Published in: PloS one 2019-12, Vol.14 (12), p.e0226574-e0226574
• Main Authors: Morris, Jodie L, Letson, Hayley L, Elliott, Lisa, Grant, Andrea L, Wilkinson, Matthew, Hazratwala, Kaushik, McEwen, Peter
• Format: Article
• Language: English
• Subjects: Analgesics; Analysis; Animal tissues; Animals; Antibacterial agents; Antibiotics; Antimicrobial agents; Bacterial infections; Bacterial Load - drug effects; Bacteriophages; Bacteriophages - physiology; Biofilms; Biology and Life Sciences; Clinical trials; Combined Modality Therapy; Dentistry; Disease Models, Animal; Engineering and Technology; Ethics; Health aspects; Immunology; Infection; Infections; Joint diseases; Joint surgery; Joints (anatomy); Male; Medical research; Medicine and Health Sciences; Methicillin; Microbiology; Phages; Prostheses; Prostheses and implants; Prosthesis-Related Infections - microbiology; Prosthesis-Related Infections - therapy; Random Allocation; Rats; Rats, Sprague-Dawley; Staphylococcal infections; Staphylococcal Infections - microbiology; Staphylococcal Infections - therapy; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - pathogenicity; Staphylococcus aureus infections; Staphylococcus infections; Studies; Surgery; Therapy; Titanium; Transplants & implants; Treatment Outcome; Vancomycin; Vancomycin - administration & dosage; Vancomycin - pharmacology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0226574

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to sham-treated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI.