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

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 shamtreated 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

Implant infections: adhesion, biofilm formation and immune evasion

Medical device-associated infections account for a large proportion of hospital-acquired infections. A variety of opportunistic pathogens can cause implant infections, depending on the type of the implant and on the anatomical site of implantation. The success of these versatile pathogens depends on rapid adhesion to virtually all biomaterial surfaces and survival in the hostile host environment. Biofilm formation on implant surfaces shelters the bacteria and encourages persistence of infection. Furthermore, implant-infecting bacteria can elude innate and adaptive host defences as well as biocides and antibiotic chemotherapies. In this Review, we explore the fundamental pathogenic mechanisms underlying implant infections, highlighting orthopaedic implants and Staphylococcus aureus as a prime example, and discuss innovative targets for preventive and therapeutic strategies

Antimicrobial titanium/silver PVD coatings on titanium

<p>Abstract</p> <p>Background</p> <p>Biofilm formation and deep infection of endoprostheses is a recurrent complication in implant surgery. Post-operative infections may be overcome by adjusting antimicrobial properties of the implant surface prior to implantation. In this work we described the development of an antimicrobial titanium/silver hard coating via the physical vapor deposition (PVD) process.</p> <p>Methods</p> <p>Coatings with a thickness of approximately 2 μm were deposited on titanium surfaces by simultaneous vaporisation of both metals in an inert argon atmosphere with a silver content of approximately 0.7 – 9% as indicated by energy dispersive X-ray analysis. On these surfaces microorganisms and eukaryotic culture cells were grown.</p> <p>Results</p> <p>The coatings released sufficient silver ions (0.5–2.3 ppb) when immersed in PBS and showed significant antimicrobial potency against <it>Staphylococcus epidermis </it>and <it>Klebsiella pneumoniae </it>strains. At the same time, no cytotoxic effects of the coatings on osteoblast and epithelial cells were found.</p> <p>Conclusion</p> <p>Due to similar mechanical performance when compared to pure titanium, the TiAg coatings should be suitable to provide antimicrobial activity on load-bearing implant surfaces.</p