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In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and
J T Mader1, J Calhoun, J Cobos
1Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1115, USA. Mader@MBIAN.UTMB.EDU
Abstract:
Antibiotic-impregnated beads are used in the dead bone space following debridement surgery to deliver local, high concentrations of antibiotics. Polymethylmethacrylate (PMMA), 2,000-molecular-weight (MW) polylactic acid (PLA), Poly(DL-lactide)-coglycolide (PL:CG; 90:10, 80:20, and 70:30), and the combination 2,000-MW PLA-70:20 PL:CG were individually mixed with clindamycin, tobramycin, or vancomycin. Beads were placed in 1 ml of phosphate-buffered saline (PBS) and incubated at 37 degrees C. The PBS was changed daily, and the removed PBS samples were stored at -70 degrees C until the antibiotic in each sample was determined by microbiological disk diffusion assay. Nondissolving PMMA beads with tobramycin and clindamycin had concentrations well above breakpoint sensitivity concentrations (i.e., the antibiotic concentrations at the transition point between bacterial killing and resistance to the antibiotic) for more than 90 days, but vancomycin concentrations dropped by day 12. ALl PLA, PL:CG, and the 2,000-MW PLA-70:30 PL:CG biodegradable beads release high concentrations of all the antibiotics in vitro for the period of time needed to treat bone infections (i.e., 4 to 8 weeks). Antibiotic-loaded PLA and PL:CG beads have the advantage of better antibiotic elution and the ability to biodegradable (thereby averting the need for secondary surgery for bead removal) compared to the PMMA beads presently used in the clinical setting.
Insights
Biodegradable antibiotic beads made from polylactic acid (PLA) and poly(lactide-co-glycolide) (PL:CG) offer superior elution for treating bone infections compared to non-dissolving polymethylmethacrylate (PMMA) beads.
Area of Science:
- Biomaterials Science
- Infectious Disease Treatment
- Drug Delivery Systems
Background:
- Antibiotic-impregnated beads are crucial for delivering high local antibiotic concentrations in dead bone spaces post-debridement.
- Current clinical practice often utilizes polymethylmethacrylate (PMMA) beads, which are non-biodegradable.
Purpose of the Study:
- To evaluate the in vitro antibiotic elution profiles of various biodegradable bead materials.
- To compare the performance of polylactic acid (PLA) and poly(lactide-co-glycolide) (PL:CG) beads with traditional PMMA beads.
Main Methods:
- Polymethylmethacrylate (PMMA), polylactic acid (PLA), and poly(lactide-co-glycolide) (PL:CG) beads were loaded with clindamycin, tobramycin, or vancomycin.
- Beads were incubated in phosphate-buffered saline (PBS) at 37°C with daily PBS changes.
- Antibiotic concentrations in PBS were quantified using microbiological disk diffusion assays.
Main Results:
- Non-dissolving PMMA beads maintained high concentrations of tobramycin and clindamycin for over 90 days, but vancomycin levels decreased by day 12.
- All tested PLA and PL:CG biodegradable beads demonstrated high antibiotic release for 4 to 8 weeks, sufficient for treating bone infections.
- Specific formulations, including 2,000-MW PLA and PLA-70:30 PL:CG, showed sustained elution of all tested antibiotics.
Conclusions:
- Biodegradable PLA and PL:CG antibiotic beads provide effective in vitro elution profiles for treating bone infections.
- These materials offer advantages over PMMA, including sustained antibiotic release and biodegradability, eliminating the need for secondary removal surgery.