Prophylactic treatment of gram-positive and gram-negative abdominal implant infections using locally delivered polyclonal antibodies

The increasing clinical incidence and host risk of biomaterial‐centered infections, as well as the reduced effectiveness of clinically relevant antibiotics to treat such infections, provide compelling reasons to develop new approaches for treating implanted biomaterials in a surgical context. We des...

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Veröffentlicht in:Journal of biomedical materials research 2002-04, Vol.60 (1), p.206-215
Hauptverfasser: Poelstra, Kornelis A., Barekzi, Nazir A., Rediske, Andrea M., Felts, Adrian G., Slunt, Jeffrey B., Grainger, David W.
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container_start_page 206
container_title Journal of biomedical materials research
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creator Poelstra, Kornelis A.
Barekzi, Nazir A.
Rediske, Andrea M.
Felts, Adrian G.
Slunt, Jeffrey B.
Grainger, David W.
description The increasing clinical incidence and host risk of biomaterial‐centered infections, as well as the reduced effectiveness of clinically relevant antibiotics to treat such infections, provide compelling reasons to develop new approaches for treating implanted biomaterials in a surgical context. We describe the direct local delivery of polyclonal human antibodies to abdominal surgical implant sites to reduce infection severity and mortality in a lethal murine model of surgical implant‐centered peritoneal infection. Surgical implant‐centered peritonitis was produced in 180 female CF‐1 mice by the direct inoculation of surgical‐grade polypropylene mesh disks placed in the peritoneal cavity with lethal doses of either methicillin‐resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. Mice randomly received a resorbable antibody delivery vehicle at the implant site: either a blank carboxymethylcellulose (CMC) aqueous gel or the same CMC gel containing 10 mg of pooled polyclonal human immunoglobulin G locally on the implant after infection, either alone or in combination with systemic doses of cefazolin or vancomycin antibiotics. Human antibodies were rapidly released (first‐order kinetics) from the gel carrier to both peritoneal fluids and serum in both infection scenarios. Inocula required for lethal infection were substantially reduced by surgery and the presence of the implant versus a closed lethal peritonitis model. Survival to 10 days with two different gram‐negative P. aeruginosa strains was significantly enhanced (p < 0.01) by the direct application of CMC gel containing antibodies alone to the surgical implant site. Human‐equivalent doses of systemic vancomycin provided a significantly improved benefit (p < 0.01) against lethal, implant‐centered, gram‐positive MRSA infection. However, locally delivered polyclonal human antibodies in combination with a range of systemic vancomycin doses against MRSA failed to improve host survival. Successful antibody therapy against gram‐negative, implant‐centered infections complements the clinically routine use of systemic antibiotics, providing a mechanism of protection independent of antibiotic resistance. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 206–215, 2002
doi_str_mv 10.1002/jbm.10069
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We describe the direct local delivery of polyclonal human antibodies to abdominal surgical implant sites to reduce infection severity and mortality in a lethal murine model of surgical implant‐centered peritoneal infection. Surgical implant‐centered peritonitis was produced in 180 female CF‐1 mice by the direct inoculation of surgical‐grade polypropylene mesh disks placed in the peritoneal cavity with lethal doses of either methicillin‐resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. Mice randomly received a resorbable antibody delivery vehicle at the implant site: either a blank carboxymethylcellulose (CMC) aqueous gel or the same CMC gel containing 10 mg of pooled polyclonal human immunoglobulin G locally on the implant after infection, either alone or in combination with systemic doses of cefazolin or vancomycin antibiotics. Human antibodies were rapidly released (first‐order kinetics) from the gel carrier to both peritoneal fluids and serum in both infection scenarios. Inocula required for lethal infection were substantially reduced by surgery and the presence of the implant versus a closed lethal peritonitis model. Survival to 10 days with two different gram‐negative P. aeruginosa strains was significantly enhanced (p &lt; 0.01) by the direct application of CMC gel containing antibodies alone to the surgical implant site. Human‐equivalent doses of systemic vancomycin provided a significantly improved benefit (p &lt; 0.01) against lethal, implant‐centered, gram‐positive MRSA infection. However, locally delivered polyclonal human antibodies in combination with a range of systemic vancomycin doses against MRSA failed to improve host survival. Successful antibody therapy against gram‐negative, implant‐centered infections complements the clinically routine use of systemic antibiotics, providing a mechanism of protection independent of antibiotic resistance. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 206–215, 2002</description><identifier>ISSN: 0021-9304</identifier><identifier>EISSN: 1097-4636</identifier><identifier>DOI: 10.1002/jbm.10069</identifier><identifier>PMID: 11835177</identifier><identifier>CODEN: JBMRBG</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject><![CDATA[Abdomen - microbiology ; Abdomen - physiology ; abdominal surgery ; Animals ; Anti-Bacterial Agents - therapeutic use ; Antibodies - administration & dosage ; Antibodies - therapeutic use ; antibody ; Biocompatible Materials ; Biological and medical sciences ; biomaterials ; Drug Implants ; Enzyme-Linked Immunosorbent Assay ; Female ; Gram-Negative Bacterial Infections - microbiology ; Gram-Negative Bacterial Infections - prevention & control ; gram-positive ; Gram-Positive Bacterial Infections - microbiology ; Gram-Positive Bacterial Infections - prevention & control ; Humans ; Immunoglobulin G - administration & dosage ; Immunoglobulin G - immunology ; Immunomodulators ; implant ; infection ; local delivery ; Medical sciences ; Methicillin Resistance ; Mice ; Pharmacology. Drug treatments ; Prosthesis-Related Infections - microbiology ; Prosthesis-Related Infections - prevention & control ; Pseudomonas Infections - microbiology ; Pseudomonas Infections - prevention & control ; Staphylococcal Infections - microbiology ; Staphylococcal Infections - prevention & control ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Technology. Biomaterials. Equipments]]></subject><ispartof>Journal of biomedical materials research, 2002-04, Vol.60 (1), p.206-215</ispartof><rights>Copyright © 2002 Wiley Periodicals, Inc.</rights><rights>2002 INIST-CNRS</rights><rights>Copyright 2002 John Wiley &amp; Sons, Inc. 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Biomed. Mater. Res</addtitle><description>The increasing clinical incidence and host risk of biomaterial‐centered infections, as well as the reduced effectiveness of clinically relevant antibiotics to treat such infections, provide compelling reasons to develop new approaches for treating implanted biomaterials in a surgical context. We describe the direct local delivery of polyclonal human antibodies to abdominal surgical implant sites to reduce infection severity and mortality in a lethal murine model of surgical implant‐centered peritoneal infection. Surgical implant‐centered peritonitis was produced in 180 female CF‐1 mice by the direct inoculation of surgical‐grade polypropylene mesh disks placed in the peritoneal cavity with lethal doses of either methicillin‐resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. Mice randomly received a resorbable antibody delivery vehicle at the implant site: either a blank carboxymethylcellulose (CMC) aqueous gel or the same CMC gel containing 10 mg of pooled polyclonal human immunoglobulin G locally on the implant after infection, either alone or in combination with systemic doses of cefazolin or vancomycin antibiotics. Human antibodies were rapidly released (first‐order kinetics) from the gel carrier to both peritoneal fluids and serum in both infection scenarios. Inocula required for lethal infection were substantially reduced by surgery and the presence of the implant versus a closed lethal peritonitis model. Survival to 10 days with two different gram‐negative P. aeruginosa strains was significantly enhanced (p &lt; 0.01) by the direct application of CMC gel containing antibodies alone to the surgical implant site. Human‐equivalent doses of systemic vancomycin provided a significantly improved benefit (p &lt; 0.01) against lethal, implant‐centered, gram‐positive MRSA infection. However, locally delivered polyclonal human antibodies in combination with a range of systemic vancomycin doses against MRSA failed to improve host survival. Successful antibody therapy against gram‐negative, implant‐centered infections complements the clinically routine use of systemic antibiotics, providing a mechanism of protection independent of antibiotic resistance. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 206–215, 2002</description><subject>Abdomen - microbiology</subject><subject>Abdomen - physiology</subject><subject>abdominal surgery</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibodies - administration &amp; dosage</subject><subject>Antibodies - therapeutic use</subject><subject>antibody</subject><subject>Biocompatible Materials</subject><subject>Biological and medical sciences</subject><subject>biomaterials</subject><subject>Drug Implants</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Gram-Negative Bacterial Infections - microbiology</subject><subject>Gram-Negative Bacterial Infections - prevention &amp; control</subject><subject>gram-positive</subject><subject>Gram-Positive Bacterial Infections - microbiology</subject><subject>Gram-Positive Bacterial Infections - prevention &amp; control</subject><subject>Humans</subject><subject>Immunoglobulin G - administration &amp; dosage</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunomodulators</subject><subject>implant</subject><subject>infection</subject><subject>local delivery</subject><subject>Medical sciences</subject><subject>Methicillin Resistance</subject><subject>Mice</subject><subject>Pharmacology. Drug treatments</subject><subject>Prosthesis-Related Infections - microbiology</subject><subject>Prosthesis-Related Infections - prevention &amp; control</subject><subject>Pseudomonas Infections - microbiology</subject><subject>Pseudomonas Infections - prevention &amp; control</subject><subject>Staphylococcal Infections - microbiology</subject><subject>Staphylococcal Infections - prevention &amp; control</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Technology. Biomaterials. 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Drug treatments</topic><topic>Prosthesis-Related Infections - microbiology</topic><topic>Prosthesis-Related Infections - prevention &amp; control</topic><topic>Pseudomonas Infections - microbiology</topic><topic>Pseudomonas Infections - prevention &amp; control</topic><topic>Staphylococcal Infections - microbiology</topic><topic>Staphylococcal Infections - prevention &amp; control</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Technology. Biomaterials. Equipments</topic><toplevel>online_resources</toplevel><creatorcontrib>Poelstra, Kornelis A.</creatorcontrib><creatorcontrib>Barekzi, Nazir A.</creatorcontrib><creatorcontrib>Rediske, Andrea M.</creatorcontrib><creatorcontrib>Felts, Adrian G.</creatorcontrib><creatorcontrib>Slunt, Jeffrey B.</creatorcontrib><creatorcontrib>Grainger, David W.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biomedical materials research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Poelstra, Kornelis A.</au><au>Barekzi, Nazir A.</au><au>Rediske, Andrea M.</au><au>Felts, Adrian G.</au><au>Slunt, Jeffrey B.</au><au>Grainger, David W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prophylactic treatment of gram-positive and gram-negative abdominal implant infections using locally delivered polyclonal antibodies</atitle><jtitle>Journal of biomedical materials research</jtitle><addtitle>J. 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Surgical implant‐centered peritonitis was produced in 180 female CF‐1 mice by the direct inoculation of surgical‐grade polypropylene mesh disks placed in the peritoneal cavity with lethal doses of either methicillin‐resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. Mice randomly received a resorbable antibody delivery vehicle at the implant site: either a blank carboxymethylcellulose (CMC) aqueous gel or the same CMC gel containing 10 mg of pooled polyclonal human immunoglobulin G locally on the implant after infection, either alone or in combination with systemic doses of cefazolin or vancomycin antibiotics. Human antibodies were rapidly released (first‐order kinetics) from the gel carrier to both peritoneal fluids and serum in both infection scenarios. Inocula required for lethal infection were substantially reduced by surgery and the presence of the implant versus a closed lethal peritonitis model. Survival to 10 days with two different gram‐negative P. aeruginosa strains was significantly enhanced (p &lt; 0.01) by the direct application of CMC gel containing antibodies alone to the surgical implant site. Human‐equivalent doses of systemic vancomycin provided a significantly improved benefit (p &lt; 0.01) against lethal, implant‐centered, gram‐positive MRSA infection. However, locally delivered polyclonal human antibodies in combination with a range of systemic vancomycin doses against MRSA failed to improve host survival. Successful antibody therapy against gram‐negative, implant‐centered infections complements the clinically routine use of systemic antibiotics, providing a mechanism of protection independent of antibiotic resistance. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 206–215, 2002</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>11835177</pmid><doi>10.1002/jbm.10069</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Abdomen - microbiology
Abdomen - physiology
abdominal surgery
Animals
Anti-Bacterial Agents - therapeutic use
Antibodies - administration & dosage
Antibodies - therapeutic use
antibody
Biocompatible Materials
Biological and medical sciences
biomaterials
Drug Implants
Enzyme-Linked Immunosorbent Assay
Female
Gram-Negative Bacterial Infections - microbiology
Gram-Negative Bacterial Infections - prevention & control
gram-positive
Gram-Positive Bacterial Infections - microbiology
Gram-Positive Bacterial Infections - prevention & control
Humans
Immunoglobulin G - administration & dosage
Immunoglobulin G - immunology
Immunomodulators
implant
infection
local delivery
Medical sciences
Methicillin Resistance
Mice
Pharmacology. Drug treatments
Prosthesis-Related Infections - microbiology
Prosthesis-Related Infections - prevention & control
Pseudomonas Infections - microbiology
Pseudomonas Infections - prevention & control
Staphylococcal Infections - microbiology
Staphylococcal Infections - prevention & control
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Technology. Biomaterials. Equipments
title Prophylactic treatment of gram-positive and gram-negative abdominal implant infections using locally delivered polyclonal antibodies
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