Cement Brand and Mixing Sequence Determine Vancomycin Elution from High-Dose PMMA Spacers

Background: High-dose vancomycin is routinely mixed into polymethylmethacrylate (PMMA) spacers for chronic periprosthetic joint infection (PJI). The precise manner by which to maximize elution remains unknown, and the impact of PMMA-antibiotic mixing sequences remains unexplored. Methods: Sixty PMMA discs (5 formulations consisting of 2 PMMA brands, 2 viscosities, presence or absence of premixed gentamicin) were mixed with 4 g of vancomycin using either a polymer-first or monomer-first sequence. Vancomycin elution was quantified over 28 days, antimicrobial activity against methicillin-sensitive Staphylococcus aureus was tested, and micro-computed tomography scans were performed to assess porosity. Elution amounts were compared with Holm-corrected t tests and are reported as the mean ± standard error. Results: Vancomycin retained bactericidal activity across all formulations. Monomer-first mixing of Palacos MV (medium-viscosity) yielded the greatest cumulative elution (2,897 ± 64 µg/mL), 120% greater than monomer-first mixing of Simplex P. A monomer-first sequence increased vancomycin elution from medium-viscosity Palacos MV by 57% compared with high-viscosity Palacos R. Polymer-first mixing of Simplex P yielded the greatest immediate elution over the first hour (415 ± 33 µg/mL), as well as a 52% greater cumulative elution amount over 28 days versus its monomer-first sequence. Premixed gentamicin only increased vancomycin elution for high-viscosity formulations. No significant differences were seen in porosity. Conclusions: The cement brand and mixing sequence significantly influenced elution of high-dose vancomycin from PMMA. Palacos MV mixed monomer-first produced the greatest cumulative antibiotic delivery, whereas polymer-first Simplex P maximized initial release. The mixing methods did not deleteriously affect PMMA integrity or antimicrobial activity. Clinical Relevance: Clinicians should consider their choice of PMMA brand, viscosity, and mixing sequence when preparing high-dose spacers in revision arthroplasty for PJI. Maximizing cumulative elution may be a clinically favorable strategy to improve PJI eradication.