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Adjuvant antibiotic-loaded bone cement: Concerns with current use and research to make it work

Adjuvant antibiotic-loaded bone cement: Concerns with current use and research to make it work
Adjuvant antibiotic-loaded bone cement: Concerns with current use and research to make it work

Antibiotic-loaded bone cement (ALBC) is broadly used to treat orthopaedic infections based on the rationale that high-dose local delivery is essential to eradicate biofilm-associated bacteria. However, ALBC formulations are empirically based on drug susceptibility from routine laboratory testing, which is known to have limited clinical relevance for biofilms. There are also dosing concerns with nonstandardized, surgeon-directed, hand-mixed formulations, which have unknown release kinetics. On the basis of our knowledge of in vivo biofilms, pathogen virulence, safety issues with nonstandardized ALBC formulations, and questions about the cost-effectiveness of ALBC, there is a need to evaluate the evidence for this clinical practice. To this end, thought leaders in the field of musculoskeletal infection (MSKI) met on 1 August 2019 to review and debate published and anecdotal information, which highlighted four major concerns about current ALBC use: (a) substantial lack of level 1 evidence to demonstrate efficacy; (b) ALBC formulations become subtherapeutic following early release, which risks induction of antibiotic resistance, and exacerbated infection from microbial colonization of the carrier; (c) the absence of standardized formulation protocols, and Food and Drug Administration-approved high-dose ALBC products to use following resection in MSKI treatment; and (d) absence of a validated assay to determine the minimum biofilm eradication concentration to predict ALBC efficacy against patient specific micro-organisms. Here, we describe these concerns in detail, and propose areas in need of research.

Antibiotic-loaded bone cement (ALBC), Biofilm Meeting, Local Antibiotics, Musculoskeletal Infection (MSKI)
0736-0266
Schwartz, Edward M.
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McLaren, Alex C.
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Sculco, Thomas P.
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Brause, Barry
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Bostrom, Mathias
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Kates, Stephen L.
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Parvizi, Javad
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Alt, Volker
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Arnold, William V
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Carli, Alberto
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Chen, Antonia F.
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Choe, Hyonmin
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Coraça-Huber, Débora C.
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Cross, Michael
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Ghert, Michelle
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Hickok, Noreen
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Jennings, Jessica Amber
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Joshi, Manjari
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Metsemakers, Willem-Jan
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Ninomiya, Mark
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Nishitani, Koheh
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Oh, Irvin
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Padgett, Douglas
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Ricciardi, Benjamin
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Saeed, Kordo
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Sendi, Parham
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Springer, Bryan
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Stoodley, Paul
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Wenke, Joseph C.
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Schwartz, Edward M.
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McLaren, Alex C.
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Sculco, Thomas P.
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Brause, Barry
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Bostrom, Mathias
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Kates, Stephen L.
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Parvizi, Javad
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Alt, Volker
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Arnold, William V
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Carli, Alberto
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Chen, Antonia F.
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Choe, Hyonmin
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Coraça-Huber, Débora C.
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Cross, Michael
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Ghert, Michelle
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Hickok, Noreen
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Jennings, Jessica Amber
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Joshi, Manjari
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Metsemakers, Willem-Jan
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Ninomiya, Mark
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Nishitani, Koheh
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Oh, Irvin
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Padgett, Douglas
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Ricciardi, Benjamin
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Saeed, Kordo
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Sendi, Parham
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Springer, Bryan
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Stoodley, Paul
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Wenke, Joseph C.
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Schwartz, Edward M., McLaren, Alex C., Sculco, Thomas P., Brause, Barry, Bostrom, Mathias, Kates, Stephen L., Parvizi, Javad, Alt, Volker, Arnold, William V, Carli, Alberto, Chen, Antonia F., Choe, Hyonmin, Coraça-Huber, Débora C., Cross, Michael, Ghert, Michelle, Hickok, Noreen, Jennings, Jessica Amber, Joshi, Manjari, Metsemakers, Willem-Jan, Ninomiya, Mark, Nishitani, Koheh, Oh, Irvin, Padgett, Douglas, Ricciardi, Benjamin, Saeed, Kordo, Sendi, Parham, Springer, Bryan, Stoodley, Paul and Wenke, Joseph C. (2020) Adjuvant antibiotic-loaded bone cement: Concerns with current use and research to make it work. Journal of Orthopaedic Research. (doi:10.1002/jor.24616).

Record type: Article

Abstract

Antibiotic-loaded bone cement (ALBC) is broadly used to treat orthopaedic infections based on the rationale that high-dose local delivery is essential to eradicate biofilm-associated bacteria. However, ALBC formulations are empirically based on drug susceptibility from routine laboratory testing, which is known to have limited clinical relevance for biofilms. There are also dosing concerns with nonstandardized, surgeon-directed, hand-mixed formulations, which have unknown release kinetics. On the basis of our knowledge of in vivo biofilms, pathogen virulence, safety issues with nonstandardized ALBC formulations, and questions about the cost-effectiveness of ALBC, there is a need to evaluate the evidence for this clinical practice. To this end, thought leaders in the field of musculoskeletal infection (MSKI) met on 1 August 2019 to review and debate published and anecdotal information, which highlighted four major concerns about current ALBC use: (a) substantial lack of level 1 evidence to demonstrate efficacy; (b) ALBC formulations become subtherapeutic following early release, which risks induction of antibiotic resistance, and exacerbated infection from microbial colonization of the carrier; (c) the absence of standardized formulation protocols, and Food and Drug Administration-approved high-dose ALBC products to use following resection in MSKI treatment; and (d) absence of a validated assay to determine the minimum biofilm eradication concentration to predict ALBC efficacy against patient specific micro-organisms. Here, we describe these concerns in detail, and propose areas in need of research.

Text
JOR-19-0809R1 Revision Submitted - Accepted Manuscript
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More information

Accepted/In Press date: 13 January 2020
e-pub ahead of print date: 30 January 2020
Additional Information: © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Keywords: Antibiotic-loaded bone cement (ALBC), Biofilm Meeting, Local Antibiotics, Musculoskeletal Infection (MSKI)

Identifiers

Local EPrints ID: 439021
URI: http://eprints.soton.ac.uk/id/eprint/439021
ISSN: 0736-0266
PURE UUID: ccceb963-defe-48fb-b8bd-8c455c97e3f8
ORCID for Kordo Saeed: ORCID iD orcid.org/0000-0003-0123-0302
ORCID for Paul Stoodley: ORCID iD orcid.org/0000-0001-6069-273X

Catalogue record

Date deposited: 01 Apr 2020 16:31
Last modified: 17 Mar 2024 05:15

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Contributors

Author: Edward M. Schwartz
Author: Alex C. McLaren
Author: Thomas P. Sculco
Author: Barry Brause
Author: Mathias Bostrom
Author: Stephen L. Kates
Author: Javad Parvizi
Author: Volker Alt
Author: William V Arnold
Author: Alberto Carli
Author: Antonia F. Chen
Author: Hyonmin Choe
Author: Débora C. Coraça-Huber
Author: Michael Cross
Author: Michelle Ghert
Author: Noreen Hickok
Author: Jessica Amber Jennings
Author: Manjari Joshi
Author: Willem-Jan Metsemakers
Author: Mark Ninomiya
Author: Koheh Nishitani
Author: Irvin Oh
Author: Douglas Padgett
Author: Benjamin Ricciardi
Author: Kordo Saeed ORCID iD
Author: Parham Sendi
Author: Bryan Springer
Author: Paul Stoodley ORCID iD
Author: Joseph C. Wenke

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