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Antibiotic loaded β-tricalcium phosphate/calcium sulfate for antimicrobial potency, prevention and killing efficacy of Pseudomonas aeruginosa and Staphylococcus aureus biofilms

Antibiotic loaded β-tricalcium phosphate/calcium sulfate for antimicrobial potency, prevention and killing efficacy of Pseudomonas aeruginosa and Staphylococcus aureus biofilms
Antibiotic loaded β-tricalcium phosphate/calcium sulfate for antimicrobial potency, prevention and killing efficacy of Pseudomonas aeruginosa and Staphylococcus aureus biofilms
This study investigated the efficacy of a biphasic synthetic β-tricalcium phosphate / calcium sulfate (β-TCP/CS) bone graft substitute for compatibility with vancomycin (V) in combination with tobramycin (T) or gentamicin (G) evidenced by the duration of potency and the prevention and killing efficacies of P. aeruginosa (PAO1) and S. aureus (SAP231) biofilms in in vitro assays. Antibiotic loaded β-TCP/CS beads were compared with antibiotic loaded beads formed from a well characterized synthetic calcium sulfate (CS) bone void filler. β-TCP/CS antibiotic loaded showed antimicrobial potency against PAO1 in a repeated Kirby-Bauer like zone of inhibition assay for 6 days compared to 8 days for CS. However, both bead types showed potency against SAP231 for 40 days. Both formulations loaded with V+T completely prevented biofilm formation (CFU below detection limits) for the 3 days of the experiment with daily fresh inoculum challenges (P < 0.001). In addition, both antibiotic loaded materials and antibiotic combinations significantly reduced the bioburden of pre grown biofilms by between 3 and 5 logs (P < 0.001) with V+G performing slightly better against PAO1 than V+T. Our data, combined with previous data on osteogenesis suggest that antibiotic loaded β-TCP/CS may have potential to stimulate osteogenesis through acting as a scaffold as well as simultaneously protecting against biofilm infection. Future in-vivo experiments and clinical investigations are warranted to more comprehensively evaluate the use of β-TCP/CS in the management of orthopaedic infections.
Biofilm, Pseudomonas aeruginosa, Staphylococcus aureus, antibiotic-loaded beads, bone graft, orthopedic infection
2045-2322
Jiang, Nan
ef83d2d6-09b2-4d7a-845a-8ffbe8a67dd3
Dusane, Devendra H.
9a47c5eb-5587-4f1d-bfd4-8548681be2bc
Brooks, Jacob R.
d82d53dd-aafb-4895-81b8-f5f41b1e2e85
Delury, Craig
3b6f0751-f41a-4480-b470-3ce001bba84a
Aiken, Sean
c029c46b-baad-4ff3-8d4f-f38807024a93
Laycock, Phillip A.
bf34e2e9-d2fd-4128-b671-7f3e25d80d8a
Stoodley, Paul
08614665-92a9-4466-806e-20c6daeb483f
Jiang, Nan
ef83d2d6-09b2-4d7a-845a-8ffbe8a67dd3
Dusane, Devendra H.
9a47c5eb-5587-4f1d-bfd4-8548681be2bc
Brooks, Jacob R.
d82d53dd-aafb-4895-81b8-f5f41b1e2e85
Delury, Craig
3b6f0751-f41a-4480-b470-3ce001bba84a
Aiken, Sean
c029c46b-baad-4ff3-8d4f-f38807024a93
Laycock, Phillip A.
bf34e2e9-d2fd-4128-b671-7f3e25d80d8a
Stoodley, Paul
08614665-92a9-4466-806e-20c6daeb483f

Jiang, Nan, Dusane, Devendra H., Brooks, Jacob R., Delury, Craig, Aiken, Sean, Laycock, Phillip A. and Stoodley, Paul (2021) Antibiotic loaded β-tricalcium phosphate/calcium sulfate for antimicrobial potency, prevention and killing efficacy of Pseudomonas aeruginosa and Staphylococcus aureus biofilms. Scientific Reports, 11 (1), [1446]. (doi:10.1038/s41598-020-80764-6).

Record type: Article

Abstract

This study investigated the efficacy of a biphasic synthetic β-tricalcium phosphate / calcium sulfate (β-TCP/CS) bone graft substitute for compatibility with vancomycin (V) in combination with tobramycin (T) or gentamicin (G) evidenced by the duration of potency and the prevention and killing efficacies of P. aeruginosa (PAO1) and S. aureus (SAP231) biofilms in in vitro assays. Antibiotic loaded β-TCP/CS beads were compared with antibiotic loaded beads formed from a well characterized synthetic calcium sulfate (CS) bone void filler. β-TCP/CS antibiotic loaded showed antimicrobial potency against PAO1 in a repeated Kirby-Bauer like zone of inhibition assay for 6 days compared to 8 days for CS. However, both bead types showed potency against SAP231 for 40 days. Both formulations loaded with V+T completely prevented biofilm formation (CFU below detection limits) for the 3 days of the experiment with daily fresh inoculum challenges (P < 0.001). In addition, both antibiotic loaded materials and antibiotic combinations significantly reduced the bioburden of pre grown biofilms by between 3 and 5 logs (P < 0.001) with V+G performing slightly better against PAO1 than V+T. Our data, combined with previous data on osteogenesis suggest that antibiotic loaded β-TCP/CS may have potential to stimulate osteogenesis through acting as a scaffold as well as simultaneously protecting against biofilm infection. Future in-vivo experiments and clinical investigations are warranted to more comprehensively evaluate the use of β-TCP/CS in the management of orthopaedic infections.

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Accepted/In Press date: 1 July 2020
e-pub ahead of print date: 14 January 2021
Published date: December 2021
Additional Information: Publisher Copyright: © 2021, The Author(s).
Keywords: Biofilm, Pseudomonas aeruginosa, Staphylococcus aureus, antibiotic-loaded beads, bone graft, orthopedic infection

Identifiers

Local EPrints ID: 445685
URI: http://eprints.soton.ac.uk/id/eprint/445685
ISSN: 2045-2322
PURE UUID: e0e2fbaa-893b-4761-8701-8e043abd2986
ORCID for Paul Stoodley: ORCID iD orcid.org/0000-0001-6069-273X

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Date deposited: 06 Jan 2021 17:36
Last modified: 17 Mar 2024 03:18

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Contributors

Author: Nan Jiang
Author: Devendra H. Dusane
Author: Jacob R. Brooks
Author: Craig Delury
Author: Sean Aiken
Author: Phillip A. Laycock
Author: Paul Stoodley ORCID iD

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