vancomycin and telavancin activity and impact on

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