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C OPYRIGHT 2012

BY

T HE J OURNAL

OF

B ONE

AND J OINT

S URGERY, I NCORPORATED

Commentary & Perspective

Antibiotic Bone Cement: Are Timing and Dosing Important Variables for Vancomycin Elution?
Commentary on an article by Tanay J. Amin, MD, et al.: Increasing the Elution of Vancomycin from High-Dose Antibiotic-Loaded Bone Cement:
A Novel Preparation Technique

Clifford B. Jones, MD
Polymethylmethacrylate (PMMA) combined with antibiotics provides a simple and efficient way to treat infection and osteomyelitis locally, provided that an adequate excisional debridement was performed initially and adjunctive systemic antibiotics are
utilized1. The PMMA provides a stable structure for total joint arthroplasty with cement and intramedullary implants for long-bone
nonunions. PMMA can fill dead space in osteomyelitis or open fractures with bone loss. The PMMA can be injected into a
medullary canal for arthroplasty2, can be made into multiple beads for open fractures with bone loss3, and can be utilized in a
custom nail for infected long-bone nonunions4. The combination of PMMA with heat-stable antibiotics such as vancomycin or
tobramycin allows for elution of the antibiotics over a time period5. Improving antibiotic elution without hampering the biomechanical nature of PMMA is desired.
In this study, two variables of PMMA (Simplex P and SmartSet MV) preparation with vancomycin were evaluated. The first
variable was quantity, or dose, of the liquid monomer. Doubling the amount of liquid monomer significantly reduced (by 33% and
35%) the amount of vancomycin elution over the six-week period of time for both Simplex P and SmartSet MV, respectively. The
reason for this is not known but could be related to increased entrapment of vancomycin within the polymer matrix. The second
variable was delayed timing of vancomycin addition to the monomer/polymer. Delaying addition of the vancomycin for thirty
seconds after the initiation of mixing significantly increased vancomycin elution (by 52% for Simplex P and by 25% for SmartSet
MV). The mechanism of this action was not fully elucidated but may be related to less vancomycin being trapped within the
polymer matrix. As with other studies, initially high vancomycin elution levels expressed during the first seven days dropped
precipitously and leveled off from one to six weeks. All mechanical testing mixtures demonstrated steep declines in strength from
one to six weeks. Simplex-P elution results were similar to SmartSet-MV results, but SmartSet-MV compression strength consistently performed below the ASTM accepted level of 70 MPa after six weeks of elution. Only 3.1% to 5.2% of the initial dosage of
vancomycin eluted over the six-week interval.
The strengths of this study relate to the different standard mixing techniques. These methods can be easily applied intraoperatively. Replicated methods of elution and biomechanical testing were utilized, allowing for translation of this study to prior
studies.
A weakness of the study is that there was no clinical testing of the different mixture techniques. Although the antibioticPMMA compounds met ASTM specifications, fracture or delamination of the PMMA would severely hamper reconstruction in a
patient with an infection at the site of a total joint prosthesis (cemented femoral stem) or a nonunion (antibiotic nail). No mention
of the systemic effects of increased vancomycin elution is noted. This study utilized Simplex P and SmartSet MV, but Palacos is
another commercial alternative being utilized. The study results (mixing ease, elution, and biomechanics) should not be extrapolated to Palacos without further investigation. Despite initially significant differences in comparative levels of vancomycin elution,
all measured levels of vancomycin elution dropped to nearly imperceptible levels for all mixtures after the initial three to five days
Disclosure: The author did not receive payments or services, either
directly or indirectly (i.e., via his institution), from a third party in
support of any aspect of this work. He, or his institution, has had a
financial relationship, in the thirty-six months prior to submission of
this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in
this work. The author has not had any other relationships, or engaged
in any other activities, that could be perceived to influence or have the
potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are
always provided with the online version of the article.

J Bone Joint Surg Am. 2012;94:e163(1-2)

http://dx.doi.org/10.2106/JBJS.L.01081

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This article was chosen to appear

electronically on September 26, 2012,
in advance of publication in a regularly
scheduled issue.

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TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG
V O LU M E 9 4-A N U M B E R 2 1 N O V E M B E R 7, 2 012
d

C O M M E N TA RY & P E R S P E C T I V E

(Figs. 1 and 2). On the basis of the small amount of total vancomycin elution of 3.1% to 5.2%, clinically relevant correlation
between the techniques of mixing vancomycin with PMMA and efficacy of infection eradication should not be assumed.
In order to improve initial antibiotic elution, addition of high-dose antibiotics to PMMA should be performed in a delayed
manner after initiation of polymerization and without use of additional monomer. Additional studies exploring optimal time
points and amounts of added antibiotics in conjunction with other commercially available PMMA products are welcomed.
Clifford B. Jones, MD
Orthopaedic Associates of Michigan,
Michigan State University/CHM,
Grand Rapids, Michigan

References
1. Jaeblon T. Polymethylmethacrylate: properties and contemporary uses in orthopaedics. J Am Acad Orthop Surg. 2010 May;18(5):297-305.
2. Della Valle C, Parvizi J, Bauer TW, DiCesare PE, Evans RP, Segreti J, Spangehl M, Watters WC 3rd, Keith M, Turkelson CM, Wies JL, Sluka P, Hitchcock K; American Academy
of Orthopaedic Surgeons. American Academy of Orthopaedic Surgeons clinical practice guideline on: the diagnosis of periprosthetic joint infections of the hip and knee.
J Bone Joint Surg Am. 2011 Jul 20;93(14):1355-7.
3. Keating JF, Blachut PA, OBrien PJ, Meek RN, Broekhuyse H. Reamed nailing of open tibial fractures: does the antibiotic bead pouch reduce the deep infection rate? J Orthop
Trauma. 1996;10(5):298-303.
4. Bhadra AK, Roberts CS. Indications for antibiotic cement nails. J Orthop Trauma. 2009 May-Jun;23(5 Suppl):S26-30.
5. Anagnostakos K, Kelm J. Enhancement of antibiotic elution from acrylic bone cement. J Biomed Mater Res B Appl Biomater. 2009 Jul;90(1):467-75.

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