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Adjuvant antibiotic‐loaded bone cement: Concerns with current use and research to make it work
Author(s) -
Schwarz 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,
CoraçaHuber Débora C.,
Cross Michael,
Ghert Michelle,
Hickok Noreen,
Jennings Jessica Amber,
Joshi Manjari,
Metsemakers WillemJan,
Ninomiya Mark,
Nishitani Kohei,
Oh Irvin,
Padgett Douglas,
Ricciardi Benjamin,
Saeed Kordo,
Sendi Parham,
Springer Bryan,
Stoodley Paul,
Wenke Joseph C.
Publication year - 2021
Publication title -
journal of orthopaedic research®
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.24616
Subject(s) - bone cement , antibiotics , adjuvant , dosing , drug delivery , intensive care medicine , medicine , food and drug administration , materials science , microbiology and biotechnology , cement , risk analysis (engineering) , pharmacology , nanotechnology , immunology , biology , metallurgy
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.