The University of Southampton
University of Southampton Institutional Repository

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.
42adf1d1-6f8e-4b3c-beed-3a5fcf91f521
McLaren, Alex C.
9bf091bf-c2e8-4478-955f-45f9777d6f88
Sculco, Thomas P.
0a6491e8-ef3b-40b7-bad3-ef7eca9e8f7c
Brause, Barry
a037502d-bb52-437c-be85-048ea79c3f1c
Bostrom, Mathias
95ead175-293c-4e66-a7fd-28a069d55297
Kates, Stephen L.
923605a9-20db-426e-bb0d-18038c16ac3b
Parvizi, Javad
6a566a16-30fe-4815-829a-5775c3273d05
Alt, Volker
19beb3ac-2c64-4507-adf4-d710f74b9726
Arnold, William V
97a31b4b-bd60-4a11-961c-1ee1aeb5c7a6
Carli, Alberto
4e995abf-cee8-4323-bc96-1c04bee163ae
Chen, Antonia F.
07feb13f-2fa2-49e8-96ae-b5a50f95bae8
Choe, Hyonmin
33a3a460-32e6-4a4d-8054-fb094a63f114
Coraça-Huber, Débora C.
fb26264c-a646-46fb-bc5b-ab40f0b10ea5
Cross, Michael
98f19aa7-9a55-4920-b7f2-e9849287b4f4
Ghert, Michelle
3ac8a824-f6b8-4531-9642-fb978ed9dbd4
Hickok, Noreen
7550726a-7df4-4852-bc6d-dbb8c284f9f6
Jennings, Jessica Amber
e9fe2a5f-f261-4cfb-8922-a77de4772dff
Joshi, Manjari
76b79503-f060-4c2d-9cba-be26549b09ff
Metsemakers, Willem-Jan
a3b49ce0-c064-452d-8236-f6b6b3953dbd
Ninomiya, Mark
0fcc0623-f1d8-41ab-b33e-522fe4068cf5
Nishitani, Koheh
590aa916-9160-48aa-92c2-ceac9c79671b
Oh, Irvin
6e4bd69e-97bf-407e-9fb6-f5df9ef7dca3
Padgett, Douglas
05c70491-50fa-42a4-96da-eff2631af042
Ricciardi, Benjamin
71c106e3-e297-43d2-913b-1d0081bd2bde
Saeed, Kordo
87cb67e5-71e8-4759-bf23-2ea00ebd8b39
Sendi, Parham
f8f316ea-140b-40a9-9b61-5410a77bd412
Springer, Bryan
bdf0a3b7-8a29-461e-98c0-c045b457ba1f
Stoodley, Paul
08614665-92a9-4466-806e-20c6daeb483f
Wenke, Joseph C.
bbce6c24-359e-4c31-9e91-02090fe17f6e
Schwartz, Edward M.
42adf1d1-6f8e-4b3c-beed-3a5fcf91f521
McLaren, Alex C.
9bf091bf-c2e8-4478-955f-45f9777d6f88
Sculco, Thomas P.
0a6491e8-ef3b-40b7-bad3-ef7eca9e8f7c
Brause, Barry
a037502d-bb52-437c-be85-048ea79c3f1c
Bostrom, Mathias
95ead175-293c-4e66-a7fd-28a069d55297
Kates, Stephen L.
923605a9-20db-426e-bb0d-18038c16ac3b
Parvizi, Javad
6a566a16-30fe-4815-829a-5775c3273d05
Alt, Volker
19beb3ac-2c64-4507-adf4-d710f74b9726
Arnold, William V
97a31b4b-bd60-4a11-961c-1ee1aeb5c7a6
Carli, Alberto
4e995abf-cee8-4323-bc96-1c04bee163ae
Chen, Antonia F.
07feb13f-2fa2-49e8-96ae-b5a50f95bae8
Choe, Hyonmin
33a3a460-32e6-4a4d-8054-fb094a63f114
Coraça-Huber, Débora C.
fb26264c-a646-46fb-bc5b-ab40f0b10ea5
Cross, Michael
98f19aa7-9a55-4920-b7f2-e9849287b4f4
Ghert, Michelle
3ac8a824-f6b8-4531-9642-fb978ed9dbd4
Hickok, Noreen
7550726a-7df4-4852-bc6d-dbb8c284f9f6
Jennings, Jessica Amber
e9fe2a5f-f261-4cfb-8922-a77de4772dff
Joshi, Manjari
76b79503-f060-4c2d-9cba-be26549b09ff
Metsemakers, Willem-Jan
a3b49ce0-c064-452d-8236-f6b6b3953dbd
Ninomiya, Mark
0fcc0623-f1d8-41ab-b33e-522fe4068cf5
Nishitani, Koheh
590aa916-9160-48aa-92c2-ceac9c79671b
Oh, Irvin
6e4bd69e-97bf-407e-9fb6-f5df9ef7dca3
Padgett, Douglas
05c70491-50fa-42a4-96da-eff2631af042
Ricciardi, Benjamin
71c106e3-e297-43d2-913b-1d0081bd2bde
Saeed, Kordo
87cb67e5-71e8-4759-bf23-2ea00ebd8b39
Sendi, Parham
f8f316ea-140b-40a9-9b61-5410a77bd412
Springer, Bryan
bdf0a3b7-8a29-461e-98c0-c045b457ba1f
Stoodley, Paul
08614665-92a9-4466-806e-20c6daeb483f
Wenke, Joseph C.
bbce6c24-359e-4c31-9e91-02090fe17f6e

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
Download (186kB)

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: 11 Aug 2022 04:02

Export record

Altmetrics

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×