Antibiotic release from PMMA spacers and PMMA beads measured with ELISA: Assessment of in vitro samples and drain fluid samples of patients
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Daniël M C Janssen1,2, Paul Willems1, Jan Geurts1
1Department of Orthopaedic Surgery, Laboratory for Experimental Orthopaedics, Research School CAPHRI, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Abstract:
For prosthetic joint infections, antibiotic loaded poly methyl methacrylate (PMMA) spacer or beads can be used to release high concentrations of antibiotics locally at the infection site, while minimizing systemic toxicity. The aim of this study is to determine in vitro and in vivo pharmacokinetic release profile of antibiotics from PMMA spacers and PMMA beads. For the in vitro experiment, the PMMA spacers or beads were submerged in phosphate-buffered saline and gentamicin concentrations were determined from collected specimen at several times points, measured with enzyme-linked immunosorbent assays (ELISA). To assess the in vivo antibiotic release profile of different spacers, wound drainage fluid samples were collected after implantation of a spacer over a period of maximum 14 days. After 48 h, the burst gentamicin concentration elution was 9862 ± 1782 ng/ml (mean ± SD) from spacers versus 38,394 ± 7071 ng/ml (mean ± SD) for beads. Over 35 days, spacers had eluted a cumulative mean concentration of 13,812 ± 3548 versus 55,048 ± 12,006 ng/ml for beads (p < 0.001). Clinical samples of patients with a Vancogenx® spacer showed higher gentamicin release than Refobacin™ spacers (p < 0.001). This is the first study that measured the release data of local antibiotics with ELISA. Compare to spacers, the exact release values of gentamicin from PMMA beads are more than 10 times higher and reached a maximum much later than spacers. This makes the use of PMMA beads more preferable to use for treatment of the infection itself.
Insights
Poly methyl methacrylate (PMMA) beads show significantly higher gentamicin release than PMMA spacers, making beads a more effective option for treating prosthetic joint infections locally.
Area of Science:
- Biomaterials Science
- Pharmacokinetics
- Infectious Diseases
Background:
- Prosthetic joint infections (PJIs) require effective local antibiotic delivery to minimize systemic toxicity.
- Poly methyl methacrylate (PMMA) spacers and beads are used for localized antibiotic elution.
- Understanding the pharmacokinetic release profiles is crucial for optimizing PJI treatment.
Purpose of the Study:
- To determine the in vitro and in vivo pharmacokinetic release profiles of antibiotics from PMMA spacers and beads.
- To compare the gentamicin release kinetics between PMMA spacers and beads.
- To evaluate the influence of different PMMA spacer brands on antibiotic release.
Main Methods:
- In vitro elution studies using phosphate-buffered saline.
- In vivo analysis of wound drainage fluid from patients.
- Quantification of gentamicin concentrations using enzyme-linked immunosorbent assays (ELISA).
Main Results:
- PMMA beads demonstrated over 10 times higher cumulative gentamicin release compared to PMMA spacers over 35 days (p < 0.001).
- Initial burst release of gentamicin was significantly higher from beads (38,394 ng/ml) than spacers (9,862 ng/ml) at 48 hours.
- Vancogenx® spacers showed higher gentamicin release than Refobacin™ spacers (p < 0.001).
Conclusions:
- PMMA beads provide superior gentamicin elution compared to PMMA spacers, suggesting greater efficacy for treating PJIs.
- The study is the first to measure local antibiotic release data using ELISA.
- PMMA beads are a more preferable option for direct infection treatment due to higher and sustained antibiotic release.
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