In Vivo Assessment of Phage and Linezolid Based Implant Coatings for Treatment of Methicillin Resistant S. aureus (MRSA) Mediated Orthopaedic Device Related Infections

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), t...

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Veröffentlicht in:PloS one 2016-06, Vol.11 (6), p.e0157626-e0157626
Hauptverfasser: Kaur, Sandeep, Harjai, Kusum, Chhibber, Sanjay
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Chhibber, Sanjay
description 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.
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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27333300</pmid><doi>10.1371/journal.pone.0157626</doi><oa>free_for_read</oa></addata></record>
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subjects Analysis
Animal models
Animals
Antibiotics
Antimicrobial agents
Bacteria
Bacterial Load - drug effects
Bacteriophages - metabolism
Biofilms
Biology and Life Sciences
Biopolymers
Calcitonin - metabolism
Chronic fatigue syndrome
Coated Materials, Biocompatible - pharmacology
Coatings
Complications and side effects
Cytokines - metabolism
Disease Models, Animal
Dosage and administration
Drug dosages
Drug resistance
Drug Resistance, Bacterial - drug effects
Drug therapy
Edema
Edema - complications
Edema - pathology
Emergence
Etiology
Femur
Health aspects
Infections
Inoculation
Joint diseases
Joint surgery
Joints - diagnostic imaging
Joints - microbiology
Joints - pathology
Joints - surgery
Linezolid
Linezolid - pharmacology
Linezolid - therapeutic use
Locomotion
Medicine and Health Sciences
Methicillin
Methicillin-Resistant Staphylococcus aureus - drug effects
Methylcellulose
Motor Activity - drug effects
Mutants
Mutation - genetics
Orthopedic appliances
Orthopedic Equipment - microbiology
Phages
Prostheses
Prostheses and Implants - adverse effects
Prosthesis-Related Infections - drug therapy
Prosthesis-Related Infections - microbiology
Prosthesis-Related Infections - pathology
Research and Analysis Methods
Resistant mutant
Staphylococcus aureus
Staphylococcus aureus infections
Staphylococcus epidermidis
Staphylococcus infections
Surgical implants
Transplants & implants
Wire
Wound Healing - drug effects
title In Vivo Assessment of Phage and Linezolid Based Implant Coatings for Treatment of Methicillin Resistant S. aureus (MRSA) Mediated Orthopaedic Device Related Infections
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