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JBJS - 2026-09-15 - Journal Article

Cement Brand and Mixing Sequence Determine Vancomycin Elution from High-Dose PMMA Spacers: An in Vitro Comparative Study.

Hammad M, Chao CA, Bostrom MP, Carli AV

biomechanicalLOE Vn = 60 PMMA discs (5 formulations, 2 mixing sequences)28-day elution period

Topics

arthroplastybasic science
PMID: 42743313DOI: 10.2106/JBJS.25.00745View on PubMed ->

Key Takeaway

Monomer-first mixing of medium-viscosity Palacos MV yields 2,897 ± 64 µg/mL cumulative vancomycin elution over 28 days—120% greater than monomer-first Simplex P—demonstrating that cement brand and mixing sequence are independent determinants of antibiotic delivery from high-dose PMMA spacers.

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Summary

This in vitro study tested whether PMMA brand, viscosity, gentamicin pre-loading, and polymer-first versus monomer-first mixing sequence affect vancomycin elution from high-dose spacers used in chronic PJI revision. Sixty discs across 5 formulations were eluted over 28 days with quantitative assay, antimicrobial activity testing against MSSA, and micro-CT porosity analysis. Monomer-first Palacos MV maximized cumulative elution (2,897 ± 64 µg/mL), polymer-first Simplex P maximized early elution (415 ± 33 µg/mL at 1 hour), and no formulation compromised PMMA structural integrity or bactericidal activity.

Key Limitation

Static in vitro elution conditions do not replicate in vivo fluid dynamics, protein binding, or tissue pharmacokinetics, so the rank-order differences between formulations may not translate proportionally to local tissue vancomycin concentrations in patients.

Original Abstract

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.