TY - JOUR
T1 - Oritavancin polymethylmethacrylate (PMMA) - Compressive strength testing and in vitro elution
AU - Schmidt-Malan, Suzannah M.
AU - Greenwood-Quaintance, Kerryl E.
AU - Berglund, Lawrence J.
AU - Mandrekar, Jayawant
AU - Patel, Robin
N1 - Funding Information:
Supported by The Medicines Company and the Mayo Clinic Materials and Structural Testing Research Core
Funding Information:
SSM reports grants from The Medicines Company, during the conduct of the study. KGQ, LB, and JM have nothing to disclose. RP reports grants from CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company.
Publisher Copyright:
© 2019 The Author(s).
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/2/12
Y1 - 2019/2/12
N2 - 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.
AB - 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.
KW - Compressive strength
KW - Elution
KW - Oritavancin
KW - Polymethylmethacrylate
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U2 - 10.1186/s13018-019-1080-6
DO - 10.1186/s13018-019-1080-6
M3 - Article
C2 - 30755223
AN - SCOPUS:85061501374
VL - 14
JO - Journal of Orthopaedic Surgery and Research
JF - Journal of Orthopaedic Surgery and Research
SN - 1749-799X
IS - 1
M1 - 43
ER -