vancomycin and telavancin activity and impact on
TRANSCRIPT
Periprosthetic joint infection (PJI) is one of the most challenging problems in orthopedicsurgery. Infection in PJI involves the adhesion of bacteria to the implant and theproduction of a biofilm from the bacterial strains [1,2]. Some bacterial strains such asstaphylococci and gram-positive bacteria cannot be completely eliminated by antibioticsand may result in necrosis of tissues surrounding an implant. Antibiotic-loaded bonecement (ALBC) is an effective treatment against infection at the implant site. With ALBC ahigher level of drug concentration is delivered to the infection site, than can be reachedby venous administration. However, the addition of antibiotics may weaken the cement’smechanical properties. Vancomycin (VAN) loaded in Palacos® R bone cement has shownantibiotic efficacy against main pathogens with sufficient drug elution in vitro, andmechanical properties [3]. Telavancin (TLV) is an investigational lipoglycopeptide antibioticthat is active against gram-positive pathogens, and is anticipated to have similar results asVAN when added to cement. In this study, two different antibiotics (VAN and TLV) withtwo types of cements (Palacos® R and Simplex® P) were compared in vitro for drugelution, efficacy and cement mechanical properties.
BACKGROUND
METHODS
CONCLUSION
Vancomycin and Telavancin Activity and Impact on Mechanical Properties When Added to
Orthopedic Bone CementSunjung Kim1 , Aaron R. Bishop2, Matthew Squire3, Heidi-Lynn Ploeg1,2,3, Warren E. Rose3,4
1University of Wisconsin – Madison, Mechanical Engineering, 2University of Wisconsin – Madison, Biomedical Engineering, 3University of Wisconsin School of
Medicine and Public, 4Univeristy of Wisconsin – Madison, School of Pharmacy
Cement Components Composition
Palacos R
(Heraeus Medical
GmbH, Wehrheim,
Germany)
Polymer
powder
Poly(methyl acrylate, methyl methacrylate) 33.8 g
Zirconium dioxide 5.9 g
Hydrous benzoyl peroxide 0.3 g
Liquid
monomer
Methyl methacrylate 18.4 g
N,N-dimethyl-p-toluidine 0.4 g
Simplex P
(Stryker
Coporation,
Kalamazoo,
Michigan, USA)
Polymer
powder
Polymethyl methacrylate 6 g
Methyl methacrylate-styrene-copolymer 29.5 g
Benzoyl Peroxide 0.45 g
Barium Sulfate, U.S.P. 4 g
Liquid
monomer
Methyl methacrylate 19.4 g
N,N-dimethyl-p-toluidine 0.52 g
Bone Cements
Sample Preparation
• Drug Elution: Disc 6 mm diameter × 4.5 mm height
• 4-point bending: Beam 75 mm × 10 mm × 3.3 mm
• Compression: Cylinder 6 mm diameter × 12 mm height
• Fracture toughness: Beam 44 mm × 10 mm × 5mm with crack length
between 4.5 mm and 5.5 mm
Antibiotic Elution
• 60-day elution into 5mL potassium phosphate buffer
• Incubated (37℃) and shaken (100 rpm)
• Drug concentration determined with HPLC and C18 column
Antibiotic Activity
• 2-week activity with daily sampling in tryptic soy broth
Bacterial Strains
• MRSA: n315 and ATCC 33591; MSSA ATCC 292131; S. epidermidis ATCC
35984
Mechanical Testing
• Performed on MTS Criterion, MTS Systens Corp., Eden Prairie, MN
• 21-day wet curing of samples in phosphate buffer solution at 21℃ before
testing
• Testing condition and methods followed ISO 5833
• Fracture surface imaged by standard scanning electron microscopy (SEM)
RESULTS
REFERENCES
• The samples with 1.0 g of VAN in Palacos R produced the highest mass of eluted antibiotic.
• Both TLV and VAN had significantly less elution from Simplex P than Palacos R.
• 0.5 – 2.0 g of VAN in Palacos R or Simplex P fully eliminated three S. aureus strains within 2 days.
• 2.0 g of TLV in Palacos R eliminated S. aureus strains but not when added to Simplex P.
• The cement’s mechanical properties were degraded by added antibiotics and 21-day wet curing
• VAN and TLV loads of 1.0 g or greater reduced compressive yield strength of Palacos R cement below the ISO
minimum.
• TLV samples tended to have larger pore sizes, and lower mechanical properties than VAN samples.
[1] E. E. MacKintosh, J. D. Patel, R. E. Marchant, and J. M. Anderson, “Effects of biomaterial surface chemistry on the adhesion and biofilm formation of Staphylococcus epidermidis in vitro,”
Journal of Biomedical Materials Research. Part A, vol. 78, no. 4, pp. 836–842, 2006. [2] H. Rohde, S. Frankenberger, U. Z ahringer, and D. Mack, “Structure, function and contribution of
polysaccharide inter-cellular adhesin (PIA) to Staphylococcus epidermidis biofilm formation and pathogenesis of biomaterial-associated infections,” European Journal of Cell
Biology,vol.89,no.1,pp.103– 111, 2010. [3] A. R. Bishop, S. Kim, M. W. Squire, W. E. Rose, and H.-L. Ploeg, “Vancomycin elution, activity and impact on mechanical properties when added to
orthopedic bone cement,” J. Mech. Behav. Biomed. Mater., vol. 87, 2018.
Figure 2. Two weeks activity data from Vancomycin (VAN) and Telavancin (TLV) at 2.0 g per packet of Palacos and Simplex cement with 103 initial CFU. VAN + Palacos [2a], VAN +
Simplex [2b], TLV + Palacos [2c], TLV + Simplex [2d]
Figure 3. Mechanical testing with Vancomycin and Telavancin in Palacos and Simplex after 21 days of wet curing. A significance level of 5% was used for all tests. An * indicates a
significant (p < 0.05) difference from Palacos R and Simplex P for each environmental condition.
Flexural Modulus Flexural Strength Compressive Yield Strength Fracture Toughness
Figure 4. SEM images of bone cement fracture surfaces from
fracture toughness samples with 2.0 g of antibiotic. VAN +
Palacos R [4a] / VAN + Simplex P [4b] / TLV + Palacos [4c] /
TLV + Simplex [4d]
Figure 1. 1 to 60 days of elution data of Vancomycin (VAN) and Telavancin (TLV) from Palacos and Simplex bone cement disk. N=15 at each time point. VAN + Palacos [1a], VAN +
Simplex [1b], TLV + Palacos [1c], TLV + Simplex [1d]
Funding: This study was supported by an investigator
initiated grant from Theravance Biopharma R&D, Inc.Presentation# 2404
October 6, 2018
[1a] [1b] [1c] [1d]
[2a] [2b] [2c] [2d]
[3a] [3b] [3c] [3d]
2.0001.0000.5000.2500.125Control
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Fra
ctu
re T
ou
gh
ness
[M
Pa V
m]
Palacos Control
Simplex Control
Palacos w/ Telavancin
Palacos w/ Vancomycin
Simplex w/ Telavancin
Simplex w/ Vancomycin
Type of Antibiotic
Added Antibiotic [gram]
*
*
* *
*
* *
**
*
[4a] [4b]
[4c] [4d]
UW Bone and JointBiomechanics Lab