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Commentary and 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, MD1
1 Orthopaedic Associates of Michigan, Michigan State University/CHM, Grand Rapids, Michigan
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This article was chosen to appear electronically on September 26, 2012, in advance of publication in a regularly scheduled issue.



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.

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 Nov 07;94(21):e163 1-2. doi: 10.2106/JBJS.L.01081
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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 antibiotic-PMMA 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 (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.
Jaeblon  T. Polymethylmethacrylate: properties and contemporary uses in orthopaedics. J Am Acad Orthop Surg.  2010 May;18(  5):297-305.
 
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.[CrossRef]
 
Keating  JF;  Blachut  PA;  O’Brien  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.[CrossRef][PubMed]
 
Bhadra  AK;  Roberts  CS. Indications for antibiotic cement nails. J Orthop Trauma.  2009 May-Jun;23(  5 Suppl):S26-30.[CrossRef]
 
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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References

Jaeblon  T. Polymethylmethacrylate: properties and contemporary uses in orthopaedics. J Am Acad Orthop Surg.  2010 May;18(  5):297-305.
 
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.[CrossRef]
 
Keating  JF;  Blachut  PA;  O’Brien  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.[CrossRef][PubMed]
 
Bhadra  AK;  Roberts  CS. Indications for antibiotic cement nails. J Orthop Trauma.  2009 May-Jun;23(  5 Suppl):S26-30.[CrossRef]
 
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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