Abstract
Staphylococcus comprises up to two-thirds of all pathogens in orthopaedic implant infections with two species respectively Staphylococcus aureus and Staphylococcus epidermidis, being the predominate etiological agents isolated. Further, with the emergence of methicillin-resistant S. aureus (MRSA), treatment of S. aureus implant infections has become more difficult, thus representing a devastating complication. Use of local delivery system consisting of S.aureus specific phage along with linezolid (incorporated in biopolymer) allowing gradual release of the two agents at the implant site represents a new, still unexplored treatment option (against orthopaedic implant infections) that has been studied in an animal model of prosthetic joint infection. Naked wire, hydroxypropyl methylcellulose (HPMC) coated wire and phage and /or linezolid coated K-wire were surgically implanted into the intra-medullary canal of mouse femur bone of respective groups followed by inoculation of S.aureus ATCC 43300(MRSA). Mice implanted with K-wire coated with both the agents i.e phage as well as linezolid (dual coated wires) showed maximum reduction in bacterial adherence, associated inflammation of the joint as well as faster resumption of locomotion and motor function of the limb. Also, all the coating treatments showed no emergence of resistant mutants. Use of dual coated implants incorporating lytic phage (capable of self-multiplication) as well as linezolid presents an attractive and aggressive early approach in preventing as well as treating implant associated infections caused by methicillin resistant S. aureus strains as assessed in a murine model of experimental joint infection.
Highlights
Staphylococcus is a major pathogen involved in post arthroplasty and orthopaedic implant related infections [1,2,3]
To develop model of post-arthroplasty infection, an orthopaedic-grade, K-wire was surgically placed into the femur followed by inoculation of S.aureus into the joint space before suturing
Since the aim of this study was to assess the efficacy of phage coated and/or antibiotic coated K-wires on the course of joint infection, doses higher than 107 and108 were not selected as these led to development of a severe purulent joint infection with > 50% mortality in mice respectively (S1 File, S1 Table, S1 Fig)
Summary
Staphylococcus is a major pathogen involved in post arthroplasty and orthopaedic implant related infections [1,2,3]. One potential therapeutic strategy is local drug delivery where antibiotics delivered locally at the implant site in high concentration can take care of pathogenic bacteria This can be achieved either by using an adequate carrier or by coating the implants (stainless steel or titanium implants) with polymers loaded with antimicrobial agent [11,12,13]. The major drawback of such system is that PMMA used is not biodegradable and is itself prone to microbial adhesion and biofilm formation [16,17,18,19] Such systems allow long term slow release of antibiotic, exposing bacteria to sub-MIC concentrations that enhance emergence of resistant mutants and infection relapse [20,21,22,23]. Dual coating involving combination of two antimicrobial agents significantly reduced (
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