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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0157626</identifier><identifier>PMID: 27333300</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2016-06, Vol.11 (6), p.e0157626-e0157626</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Kaur et al 2016 Kaur et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-e68994356879db3a4bb45b86b8201a3fa809ab8ccc90ea6485e3558720b218d23</citedby><cites>FETCH-LOGICAL-c725t-e68994356879db3a4bb45b86b8201a3fa809ab8ccc90ea6485e3558720b218d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917197/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917197/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27333300$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Becker, Karsten</contributor><creatorcontrib>Kaur, Sandeep</creatorcontrib><creatorcontrib>Harjai, Kusum</creatorcontrib><creatorcontrib>Chhibber, Sanjay</creatorcontrib><title>In Vivo Assessment of Phage and Linezolid Based Implant Coatings for Treatment of Methicillin Resistant S. aureus (MRSA) Mediated Orthopaedic Device Related Infections</title><title>PloS one</title><addtitle>PLoS One</addtitle><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. 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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. 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drug effects</topic><topic>Bacteriophages - metabolism</topic><topic>Biofilms</topic><topic>Biology and Life Sciences</topic><topic>Biopolymers</topic><topic>Calcitonin - metabolism</topic><topic>Chronic fatigue syndrome</topic><topic>Coated Materials, Biocompatible - pharmacology</topic><topic>Coatings</topic><topic>Complications and side effects</topic><topic>Cytokines - metabolism</topic><topic>Disease Models, Animal</topic><topic>Dosage and administration</topic><topic>Drug dosages</topic><topic>Drug resistance</topic><topic>Drug Resistance, Bacterial - drug effects</topic><topic>Drug therapy</topic><topic>Edema</topic><topic>Edema - complications</topic><topic>Edema - pathology</topic><topic>Emergence</topic><topic>Etiology</topic><topic>Femur</topic><topic>Health aspects</topic><topic>Infections</topic><topic>Inoculation</topic><topic>Joint diseases</topic><topic>Joint surgery</topic><topic>Joints - diagnostic imaging</topic><topic>Joints - microbiology</topic><topic>Joints - pathology</topic><topic>Joints - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaur, Sandeep</au><au>Harjai, Kusum</au><au>Chhibber, Sanjay</au><au>Becker, Karsten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vivo Assessment of Phage and Linezolid Based Implant Coatings for Treatment of Methicillin Resistant S. aureus (MRSA) Mediated Orthopaedic Device Related Infections</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-06-22</date><risdate>2016</risdate><volume>11</volume><issue>6</issue><spage>e0157626</spage><epage>e0157626</epage><pages>e0157626-e0157626</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</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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recordid | cdi_plos_journals_1799178726 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
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 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T06%3A33%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20Vivo%20Assessment%20of%20Phage%20and%20Linezolid%20Based%20Implant%20Coatings%20for%20Treatment%20of%20Methicillin%20Resistant%20S.%20aureus%20(MRSA)%20Mediated%20Orthopaedic%20Device%20Related%20Infections&rft.jtitle=PloS%20one&rft.au=Kaur,%20Sandeep&rft.date=2016-06-22&rft.volume=11&rft.issue=6&rft.spage=e0157626&rft.epage=e0157626&rft.pages=e0157626-e0157626&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0157626&rft_dat=%3Cgale_plos_%3EA456433849%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1799178726&rft_id=info:pmid/27333300&rft_galeid=A456433849&rft_doaj_id=oai_doaj_org_article_2605c0efa589471aa047d1d47e02779b&rfr_iscdi=true |