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

Sebastian, Sujeesh LU orcid ; Tandberg, Felix ; Liu, Yang LU ; Raina, Deepak B LU ; Tägil, Magnus LU ; Collin, Mattias LU orcid and Lidgren, Lars LU (2022) In Bone & joint research 11(11). p.787-802
Abstract

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... (More)

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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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antimicrobial resistance, Biofilm, Biomaterial, Bone infections, Calcium sulphate, Hydroxyapatite, Rifampicin, gentamicin, vancomycin, antibiotics, composites, hydroxyapatite, strains
in
Bone & joint research
volume
11
issue
11
pages
16 pages
publisher
British Editorial Society of Bone & Joint Surgery
external identifiers
  • pmid:36349950
  • scopus:85144638775
ISSN
2046-3758
DOI
10.1302/2046-3758.1111.BJR-2022-0101.R1
language
English
LU publication?
yes
id
bfb105f9-8aa3-4d3e-80bb-5f76ebebaa7e
date added to LUP
2022-11-14 08:35:28
date last changed
2024-06-13 22:24:12
@article{bfb105f9-8aa3-4d3e-80bb-5f76ebebaa7e,
  abstract     = {{<p>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).</p><p>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 <br>
 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.<br>
 </p><p>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 <br>
 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 <br>
 S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF.<br>
 </p><p>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: <br>
 Bone Joint Res 2022;11(11):787-802.<br>
 </p>}},
  author       = {{Sebastian, Sujeesh and Tandberg, Felix and Liu, Yang and Raina, Deepak B and Tägil, Magnus and Collin, Mattias and Lidgren, Lars}},
  issn         = {{2046-3758}},
  keywords     = {{Antimicrobial resistance; Biofilm; Biomaterial; Bone infections; Calcium sulphate; Hydroxyapatite; Rifampicin; gentamicin; vancomycin; antibiotics; composites; hydroxyapatite; strains}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{787--802}},
  publisher    = {{British Editorial Society of Bone & Joint Surgery}},
  series       = {{Bone & joint research}},
  title        = {{Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin}},
  url          = {{http://dx.doi.org/10.1302/2046-3758.1111.BJR-2022-0101.R1}},
  doi          = {{10.1302/2046-3758.1111.BJR-2022-0101.R1}},
  volume       = {{11}},
  year         = {{2022}},
}