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Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin

AIMS: There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a c...

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Autores principales: Sebastian, Sujeesh, Tandberg, Felix, Liu, Yang, Raina, Deepak B., Tägil, Magnus, Collin, Mattias, Lidgren, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The British Editorial Society of Bone & Joint Surgery 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680205/
https://www.ncbi.nlm.nih.gov/pubmed/36349950
http://dx.doi.org/10.1302/2046-3758.1111.BJR-2022-0101.R1
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author Sebastian, Sujeesh
Tandberg, Felix
Liu, Yang
Raina, Deepak B.
Tägil, Magnus
Collin, Mattias
Lidgren, Lars
author_facet Sebastian, Sujeesh
Tandberg, Felix
Liu, Yang
Raina, Deepak B.
Tägil, Magnus
Collin, Mattias
Lidgren, Lars
author_sort Sebastian, Sujeesh
collection PubMed
description AIMS: There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). METHODS: The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. RESULTS: Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. CONCLUSION: Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802.
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spelling pubmed-96802052022-11-23 Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin Sebastian, Sujeesh Tandberg, Felix Liu, Yang Raina, Deepak B. Tägil, Magnus Collin, Mattias Lidgren, Lars Bone Joint Res Biomaterials AIMS: There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). METHODS: The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. RESULTS: Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. CONCLUSION: Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802. The British Editorial Society of Bone & Joint Surgery 2022-11-15 /pmc/articles/PMC9680205/ /pubmed/36349950 http://dx.doi.org/10.1302/2046-3758.1111.BJR-2022-0101.R1 Text en © 2022 Author(s) et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Biomaterials
Sebastian, Sujeesh
Tandberg, Felix
Liu, Yang
Raina, Deepak B.
Tägil, Magnus
Collin, Mattias
Lidgren, Lars
Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin
title Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin
title_full Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin
title_fullStr Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin
title_full_unstemmed Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin
title_short Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin
title_sort extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin
topic Biomaterials
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680205/
https://www.ncbi.nlm.nih.gov/pubmed/36349950
http://dx.doi.org/10.1302/2046-3758.1111.BJR-2022-0101.R1
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