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Commentary and Perspective   |    
An Important Backdrop to the Continued Discussion on the Use of Antibiotic-Containing Bone CementsCommentary on an article by Jill Meyer, PhD, et al.: “Vacuum-Mixing Significantly Changes Antibiotic Elution Characteristics of Commercially Available Antibiotic-Impregnated Bone Cements”
Anton E. Bowden, PhD
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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 © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Nov 16;93(22):e135 1-2. doi: 10.2106/JBJS.K.01144
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The use of antibiotic-containing polymethylmethacrylate, or antibiotic PMMA, in revision of a total hip or total knee replacement due to a previous infection is currently accepted practice. Additionally, despite lack of regulatory approval in the United States, the “off-label” use of antibiotic PMMA for primary arthroplasty by orthopaedic surgeons is substantial and has continued to increase. The widespread use of antibiotic PMMA in total joint replacement provides ample clinical relevance to the article by Meyer et al. regarding the effects of vacuum-mixing on six widely used antibiotic PMMA formulations.
One of the strengths of the work is the logical study design. The authors utilize a previously reported methodology for creating pellets of uniform consistency with virtually identical geometry1. Thirty pellets of each antibiotic (fifteen vacuum-mixed and fifteen atmospheric) were evaluated each day during a five-day elution protocol and were compared between groups as well as against identically prepared nonantibiotic controls for the same PMMA. Eluent from each pellet for each day was evaluated for antibiotic concentration and for the effective zone of bacterial growth inhibition. The authors confirmed that their in vitro study results were comparable with previously published in vivo elution characteristics of antibiotic PMMA where available2.
A first approach to selecting an antibiotic PMMA for arthroplasty might rely on a clinician's experience with the same antibiotic in other contexts. However, the authors’ results confirm that the choice of the PMMA formulation, as well as the method of preparation, with or without vacuum-mixing, play a significant role in the antibiotic elution characteristics. The combination of these factors on antibiotic effectiveness was shown to be nonintuitive and brand-specific. For example, vacuum-mixing increased the effective elution time of some combinations, while decreasing the effective elution time of others. Additionally, the aminoglycoside content of an antibiotic PMMA was not associated with antimicrobial activity or antibiotic elution time. For example, two of the products with the smallest aminoglycoside content had the greatest potency. In these cases, the authors reasonably extrapolate that PMMA viscosity and porosity interact with the antibiotics to produce the measured effects.
Given that the authors were investigating U.S. Food and Drug Administration-approved antibiotic PMMA formulations, it might be expected that PMMA suppliers would provide guidance with respect to the optimal preparation conditions for their product. However, Meyer et al. report that only one of the six PMMA products had any specific guidance as to the use of vacuum or atmospheric pressure mixing.
Vacuum-mixing has been shown to increase the strength of PMMA3,4, while the addition of antibiotic has been shown to decrease the strength of PMMA5. Although the clinical relevance of these results is still unclear, it seems likely that those reported results have impacted surgeon perception of the need for vacuum mixing to offset potential decreases in strength due to adding antibiotic. However, the results reported by Meyer et al. make it clear that such an overgeneralization would be unwise since the elution characteristics of several commonly used antibiotic PMMA formulations are negatively impacted by vacuum-mixing. Thus, the ideal preparation of each formulation must be evaluated independently.
A shortcoming of the work stems from several reported issues, such as sample contamination and statistical outliers. These are well described in the text, and the authors used a reasonable technique to account for the missing data. These issues detract from the overall impact of the work, but leave the authors’ conclusions intact.
In summary, the article by Meyer et al. provides an important backdrop to the continued discussion on the use of antibiotic PMMA in total joint replacement.
Squire  MW;  Ludwig  BJ;  Thompson  JR;  Jagodzinski  J;  Hall  D;  Andes  D. Premixed antibiotic bone cement: an in vitro comparison of antimicrobial efficacy. J Arthroplasty.  2008;23(  6 Suppl 1):110-4.[PubMed][CrossRef]
 
Sterling  GJ;  Crawford  S;  Potter  JH;  Koerbin  G;  Crawford  R. The pharmacokinetics of Simplex-tobramycin bone cement. J Bone Joint Surg Br.  2003;85:646-9.[PubMed]
 
Lewis  G. Fatigue testing and performance of acrylic bone-cement materials: state-of-the-art review. J Biomed Mater Res B Appl Biomater.  2003;66:457-86.[PubMed][CrossRef]
 
Lidgren  L;  Bodelind  B;  Möller  J. Bone cement improved by vacuum mixing and chilling. Acta Orthop Scand.  1987;58:27-32.[PubMed][CrossRef]
 
Lewis  G. Properties of antibiotic-loaded acrylic bone cements for use in cemented arthroplasties: a state-of-the-art review. J Biomed Mater Res B Appl Biomater.  2009;89B:558-74.[CrossRef]
 

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References

Squire  MW;  Ludwig  BJ;  Thompson  JR;  Jagodzinski  J;  Hall  D;  Andes  D. Premixed antibiotic bone cement: an in vitro comparison of antimicrobial efficacy. J Arthroplasty.  2008;23(  6 Suppl 1):110-4.[PubMed][CrossRef]
 
Sterling  GJ;  Crawford  S;  Potter  JH;  Koerbin  G;  Crawford  R. The pharmacokinetics of Simplex-tobramycin bone cement. J Bone Joint Surg Br.  2003;85:646-9.[PubMed]
 
Lewis  G. Fatigue testing and performance of acrylic bone-cement materials: state-of-the-art review. J Biomed Mater Res B Appl Biomater.  2003;66:457-86.[PubMed][CrossRef]
 
Lidgren  L;  Bodelind  B;  Möller  J. Bone cement improved by vacuum mixing and chilling. Acta Orthop Scand.  1987;58:27-32.[PubMed][CrossRef]
 
Lewis  G. Properties of antibiotic-loaded acrylic bone cements for use in cemented arthroplasties: a state-of-the-art review. J Biomed Mater Res B Appl Biomater.  2009;89B:558-74.[CrossRef]
 
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