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Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model

The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial pep...

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Autores principales: Windolf, Ceylan D., Lögters, Tim, Scholz, Martin, Windolf, Joachim, Flohé, Sascha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275259/
https://www.ncbi.nlm.nih.gov/pubmed/25536060
http://dx.doi.org/10.1371/journal.pone.0115940
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author Windolf, Ceylan D.
Lögters, Tim
Scholz, Martin
Windolf, Joachim
Flohé, Sascha
author_facet Windolf, Ceylan D.
Lögters, Tim
Scholz, Martin
Windolf, Joachim
Flohé, Sascha
author_sort Windolf, Ceylan D.
collection PubMed
description The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial peptide lysostaphin in the context of bone infections. In a standardized implant-associated bone infection model in mice beta-irradiated lysostaphin-coated titanium plates were compared with uncoated plates. Coating of the implant was established with a poly(D,L)-lactide matrix (PDLLA) comprising lysostaphin formulated in a stabilizing and protecting solution (SPS). All mice were osteotomized and infected with a defined count of SA. Fractures were fixed with lysostaphin-coated locking plates. Plates uncoated or PDLLA-coated served as controls. All mice underwent debridement and lavage on Days 7, 14, 28 to determine the bacterial load and local immune reaction. Fracture healing was quantified by conventional radiography. On Day 7 bacterial growth in the lavages of mice with lysostaphin-coated plates showed a significantly lower count to the control groups. Moreover, in the lysostaphin-coated plate groups complete fracture healing were observed on Day 28. The fracture consolidation was accompanied by a diminished local immune reaction. However, control groups developed an osteitis with lysis or destruction of the bone and an evident local immune response. The presented approach of terminally sterilized lysostaphin-coated implants appears to be a promising therapeutic approach for low grade infection or as prophylactic strategy in high risk fracture care e.g. after severe open fractures.
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spelling pubmed-42752592014-12-31 Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model Windolf, Ceylan D. Lögters, Tim Scholz, Martin Windolf, Joachim Flohé, Sascha PLoS One Research Article The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial peptide lysostaphin in the context of bone infections. In a standardized implant-associated bone infection model in mice beta-irradiated lysostaphin-coated titanium plates were compared with uncoated plates. Coating of the implant was established with a poly(D,L)-lactide matrix (PDLLA) comprising lysostaphin formulated in a stabilizing and protecting solution (SPS). All mice were osteotomized and infected with a defined count of SA. Fractures were fixed with lysostaphin-coated locking plates. Plates uncoated or PDLLA-coated served as controls. All mice underwent debridement and lavage on Days 7, 14, 28 to determine the bacterial load and local immune reaction. Fracture healing was quantified by conventional radiography. On Day 7 bacterial growth in the lavages of mice with lysostaphin-coated plates showed a significantly lower count to the control groups. Moreover, in the lysostaphin-coated plate groups complete fracture healing were observed on Day 28. The fracture consolidation was accompanied by a diminished local immune reaction. However, control groups developed an osteitis with lysis or destruction of the bone and an evident local immune response. The presented approach of terminally sterilized lysostaphin-coated implants appears to be a promising therapeutic approach for low grade infection or as prophylactic strategy in high risk fracture care e.g. after severe open fractures. Public Library of Science 2014-12-23 /pmc/articles/PMC4275259/ /pubmed/25536060 http://dx.doi.org/10.1371/journal.pone.0115940 Text en © 2014 Windolf et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Windolf, Ceylan D.
Lögters, Tim
Scholz, Martin
Windolf, Joachim
Flohé, Sascha
Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model
title Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model
title_full Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model
title_fullStr Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model
title_full_unstemmed Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model
title_short Lysostaphin-Coated Titan-Implants Preventing Localized Osteitis by Staphylococcus aureus in a Mouse Model
title_sort lysostaphin-coated titan-implants preventing localized osteitis by staphylococcus aureus in a mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275259/
https://www.ncbi.nlm.nih.gov/pubmed/25536060
http://dx.doi.org/10.1371/journal.pone.0115940
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