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Oritavancin polymethylmethacrylate (PMMA)—compressive strength testing and in vitro elution

BACKGROUND: Polymethylmethacrylate (PMMA) is used for local antimicrobial delivery in orthopedic infection. Oritavancin is a long half-life lipoglycopeptide with broad activity against Gram-positive bacteria. Herein, we addressed if 7.5% w/w oritavancin mixed into PMMA affects PMMA strength and whet...

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Autores principales: Schmidt-Malan, Suzannah M., Greenwood-Quaintance, Kerryl E., Berglund, Lawrence J., Mandrekar, Jayawant, Patel, Robin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373086/
https://www.ncbi.nlm.nih.gov/pubmed/30755223
http://dx.doi.org/10.1186/s13018-019-1080-6
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author Schmidt-Malan, Suzannah M.
Greenwood-Quaintance, Kerryl E.
Berglund, Lawrence J.
Mandrekar, Jayawant
Patel, Robin
author_facet Schmidt-Malan, Suzannah M.
Greenwood-Quaintance, Kerryl E.
Berglund, Lawrence J.
Mandrekar, Jayawant
Patel, Robin
author_sort Schmidt-Malan, Suzannah M.
collection PubMed
description BACKGROUND: Polymethylmethacrylate (PMMA) is used for local antimicrobial delivery in orthopedic infection. Oritavancin is a long half-life lipoglycopeptide with broad activity against Gram-positive bacteria. Herein, we addressed if 7.5% w/w oritavancin mixed into PMMA affects PMMA strength and whether it elutes from PMMA, compared to vancomycin. METHODS: Elution was assessed by placing an oritavancin- or vancomycin-loaded bead in a flow system with human plasma. Compressive strength of bland compared to oritavancin- or vancomycin-loaded PMMA was assessed after 0, 3, and 7 days of soaking in 1 ml of pooled normal human plasma at 37 °C, by testing to failure in axial compression using a servo-hydraulic testing machine. RESULTS: Median compressive strength on days 0, 3, and 7 for bland PMMA compared to oritavancin- or vancomycin-loaded PMMA was 80.1, 79.4, and 72.4 MPa, respectively; 93.3, 86.4, and 65.3 MPa, respectively; and 97.8, 82.7, and 65.9 MPa, respectively. Oritavancin reduced PMMA compressive strength after 3 and 7 days (P = 0.0250 and 0.0039, respectively), whereas vancomycin reduced the PMMA compressive strength after 0, 3, and 7 days (P = 0.0039, 0.0039, and 0.0062, respectively) as compared to bland PMMA. Oritavancin-loaded PMMA had higher compressive strength than vancomycin-loaded PMMA on days 3 and 7 (P = 0.0039 and 0.0062, respectively). Compressive elastic moduli were 1226, 1299, and 1394 MPa for bland PMMA; 1253, 1078, and 1245 MPa for oritavancin-loaded PMMA; and 986, 879, and 779 MPa for vancomycin-loaded PMMA on days 0, 3 and 7, respectively. Oritavancin-loaded PMMA had higher compressive elastic moduli than vancomycin-loaded PMMA on days 0 and 7 (P = 0.0250 and 0.0062, respectively). Following polymerization, 1.0% and 51.9% of the initial amount of oritavancin and vancomycin were detected, respectively. C(max), T(max), and AUC(0–24) were 1.7 μg/ml, 2 h, and 11.4 μg/ml for oritavancin and 21.4 μg/ml, 2 h, and 163.9 μg/ml for vancomycin, respectively. CONCLUSIONS: Oritavancin-loaded PMMA had higher compressive strength than vancomycin-loaded PMMA on days 3 and 7 and higher compressive elastic moduli than vancomycin-loaded PMMA on days 0 and 7. However, proportionally less oritavancin than vancomycin eluted out of PMMA.
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spelling pubmed-63730862019-02-25 Oritavancin polymethylmethacrylate (PMMA)—compressive strength testing and in vitro elution Schmidt-Malan, Suzannah M. Greenwood-Quaintance, Kerryl E. Berglund, Lawrence J. Mandrekar, Jayawant Patel, Robin J Orthop Surg Res Research Article BACKGROUND: Polymethylmethacrylate (PMMA) is used for local antimicrobial delivery in orthopedic infection. Oritavancin is a long half-life lipoglycopeptide with broad activity against Gram-positive bacteria. Herein, we addressed if 7.5% w/w oritavancin mixed into PMMA affects PMMA strength and whether it elutes from PMMA, compared to vancomycin. METHODS: Elution was assessed by placing an oritavancin- or vancomycin-loaded bead in a flow system with human plasma. Compressive strength of bland compared to oritavancin- or vancomycin-loaded PMMA was assessed after 0, 3, and 7 days of soaking in 1 ml of pooled normal human plasma at 37 °C, by testing to failure in axial compression using a servo-hydraulic testing machine. RESULTS: Median compressive strength on days 0, 3, and 7 for bland PMMA compared to oritavancin- or vancomycin-loaded PMMA was 80.1, 79.4, and 72.4 MPa, respectively; 93.3, 86.4, and 65.3 MPa, respectively; and 97.8, 82.7, and 65.9 MPa, respectively. Oritavancin reduced PMMA compressive strength after 3 and 7 days (P = 0.0250 and 0.0039, respectively), whereas vancomycin reduced the PMMA compressive strength after 0, 3, and 7 days (P = 0.0039, 0.0039, and 0.0062, respectively) as compared to bland PMMA. Oritavancin-loaded PMMA had higher compressive strength than vancomycin-loaded PMMA on days 3 and 7 (P = 0.0039 and 0.0062, respectively). Compressive elastic moduli were 1226, 1299, and 1394 MPa for bland PMMA; 1253, 1078, and 1245 MPa for oritavancin-loaded PMMA; and 986, 879, and 779 MPa for vancomycin-loaded PMMA on days 0, 3 and 7, respectively. Oritavancin-loaded PMMA had higher compressive elastic moduli than vancomycin-loaded PMMA on days 0 and 7 (P = 0.0250 and 0.0062, respectively). Following polymerization, 1.0% and 51.9% of the initial amount of oritavancin and vancomycin were detected, respectively. C(max), T(max), and AUC(0–24) were 1.7 μg/ml, 2 h, and 11.4 μg/ml for oritavancin and 21.4 μg/ml, 2 h, and 163.9 μg/ml for vancomycin, respectively. CONCLUSIONS: Oritavancin-loaded PMMA had higher compressive strength than vancomycin-loaded PMMA on days 3 and 7 and higher compressive elastic moduli than vancomycin-loaded PMMA on days 0 and 7. However, proportionally less oritavancin than vancomycin eluted out of PMMA. BioMed Central 2019-02-12 /pmc/articles/PMC6373086/ /pubmed/30755223 http://dx.doi.org/10.1186/s13018-019-1080-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Schmidt-Malan, Suzannah M.
Greenwood-Quaintance, Kerryl E.
Berglund, Lawrence J.
Mandrekar, Jayawant
Patel, Robin
Oritavancin polymethylmethacrylate (PMMA)—compressive strength testing and in vitro elution
title Oritavancin polymethylmethacrylate (PMMA)—compressive strength testing and in vitro elution
title_full Oritavancin polymethylmethacrylate (PMMA)—compressive strength testing and in vitro elution
title_fullStr Oritavancin polymethylmethacrylate (PMMA)—compressive strength testing and in vitro elution
title_full_unstemmed Oritavancin polymethylmethacrylate (PMMA)—compressive strength testing and in vitro elution
title_short Oritavancin polymethylmethacrylate (PMMA)—compressive strength testing and in vitro elution
title_sort oritavancin polymethylmethacrylate (pmma)—compressive strength testing and in vitro elution
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373086/
https://www.ncbi.nlm.nih.gov/pubmed/30755223
http://dx.doi.org/10.1186/s13018-019-1080-6
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