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Antimicrobial release kinetics from polymethylmethacrylate in a novel continuous flow chamber
Archie C Perry1, Mark S Rouse, Yasmin Khaliq
1Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Abstract:
Polymethylmethacrylate is used for local delivery of antimicrobials in the treatment of musculoskeletal infections. A novel continuous flow chamber system was designed to measure in vitro antimicrobial release. Three-millimeter beads containing amikacin, gentamicin, tobramycin, or vancomycin [concentration of 7.5% (weight per weight)] were placed individually in a continuous flow chamber with a total volume of 1 mL Kreb's Ringer buffer flowing at 1 mL/hour. Effluent was sampled hourly for 24 hours and then every 2 hours up to 48 hours; antimicrobial concentrations were measured in triplicate by bioassay. The mean peak concentrations were 40.9, 30.1, 30.0, and 19.1 microg/mL; the mean areas under the concentration time curves (Time 0 to infinity) were 263, 327, 110, and 180 hours x microg/mL of antibiotic; and the mean percentages of initial amount of antimicrobial released were 11.7%, 14.5%, 6.6%, and 10.9% for tobramycin, gentamicin, amikacin, and vancomycin, respectively. The results for each polymethylmethacrylate-antimicrobial agent combination were reproducible. In contrast to other in vitro elution systems, this novel system operates under the premise that there is dynamic flow surrounding polymethylmethacrylate in vivo and permits rapid in vitro comparison of the relative release of antimicrobial agents from polymethylmethacrylate.
Insights
This study introduces a new system for measuring antimicrobial release from polymethylmethacrylate beads used in treating bone infections. The system allows for rapid comparison of antibiotic elution profiles, aiding in treatment selection.
Area of Science:
- Biomaterials Science
- Pharmacology
- Infectious Diseases
Background:
- Polymethylmethacrylate (PMMA) is utilized for localized antimicrobial delivery in musculoskeletal infections.
- Accurate in vitro assessment of antimicrobial release from PMMA is crucial for optimizing treatment efficacy.
Purpose of the Study:
- To develop and validate a novel continuous flow chamber system for quantifying in vitro antimicrobial release from PMMA beads.
- To compare the elution profiles of amikacin, gentamicin, tobramycin, and vancomycin from PMMA under dynamic flow conditions.
Main Methods:
- A continuous flow chamber system with Kreb's Ringer buffer simulating in vivo conditions was employed.
- PMMA beads (3mm) loaded with 7.5% (w/w) antibiotics were subjected to a flow rate of 1 mL/hour.
- Effluent was collected over 48 hours, and antibiotic concentrations were determined by bioassay in triplicate.
Main Results:
- Reproducible elution results were obtained for each PMMA-antibiotic combination.
- Mean peak concentrations varied among antibiotics, with tobramycin showing the highest.
- Mean cumulative release percentages over 48 hours were 11.7% (tobramycin), 14.5% (gentamicin), 6.6% (amikacin), and 10.9% (vancomycin).
Conclusions:
- The novel continuous flow system accurately measures and compares in vitro antimicrobial release from PMMA.
- This system provides a more physiologically relevant model for evaluating PMMA-based drug delivery compared to static systems.
- The findings support the use of this system for rapid in vitro comparison of antimicrobial elution from PMMA, aiding in the selection of appropriate antibiotics for musculoskeletal infections.