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.