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Updated: Feb 2, 2026

Treatment with Vancomycin Loaded Calcium Sulphate and Autogenous Bone in an Improved Rabbit Model of Bone Infection
Published on: March 14, 2019
In Vitro Efficacy of Antibiotics Released from Calcium Sulfate Bone Void Filler Beads
Phillip A Laycock1, John J Cooper2, Robert P Howlin3
1Biocomposites Ltd., Keele Science Park, Keele, Staffordshire ST5 5NL, UK. pl@biocomposites.com.
Abstract:
15 different antibiotics were individually mixed with commercially available calcium sulfate bone void filler beads. The antibiotics were: amikacin, ceftriaxone, cefuroxime, ciprofloxacin, clindamycin, colistamethate sodium, daptomycin, gentamicin, imipenem/cilastatin, meropenem, nafcillin, rifampicin, teicoplanin, tobramycin and vancomycin. The efficacy of specific released antibiotics was validated by zone of inhibition (ZOI) testing using a modified Kirby⁻Bauer disk diffusion method against common periprosthetic joint infection pathogens. With a subset of experiments (daptomycin, rifampin, vancomycin alone and rifampin and vancomycin in combination), we investigated how release varied over 15 days using a repeated ZOI assay. We also tested the ability of these beads to kill biofilms formed by Staphylococcus epidermidis 35984, a prolific biofilm former. The results suggested that certain antibiotics could be combined and released from calcium sulfate with retained antibacterial efficacy. The daptomycin and rifampin plus vancomycin beads showed antimicrobial efficacy for the full 15 days of testing and vancomycin in combination with rifampin prevented resistant mutants. In the biofilm killing assay, all of the antibiotic combinations showed a significant reduction in biofilm bacteria after 24 h. The exposure time was an important factor in the amount of killing, and varied among the antibiotics.
Insights
Calcium sulfate bone void fillers effectively release 15 antibiotics, maintaining antibacterial efficacy against infection pathogens. Combinations like daptomycin and rifampin/vancomycin show sustained antimicrobial activity and biofilm eradication.
Area of Science:
- Biomaterials Science
- Infectious Disease Research
- Antibiotic Efficacy
Background:
- Periprosthetic joint infections (PJIs) are a significant complication in orthopedic surgery.
- Antibiotic-eluting bone void fillers are crucial for treating and preventing PJIs.
- Calcium sulfate is a commonly used, resorbable carrier for antibiotic delivery.
Purpose of the Study:
- To evaluate the sustained release and antibacterial efficacy of 15 different antibiotics incorporated into calcium sulfate bone void filler beads.
- To assess the ability of antibiotic-loaded beads to eradicate biofilms formed by common pathogens.
- To investigate the long-term efficacy and potential for preventing resistance with specific antibiotic combinations.
Main Methods:
- Fifteen antibiotics were individually mixed with calcium sulfate bone void filler beads.
- Antibiotic efficacy was validated using zone of inhibition (ZOI) testing against standard PJI pathogens.
- Repeated ZOI assays over 15 days assessed antibiotic release kinetics for select antibiotics (daptomycin, rifampin, vancomycin).
- Biofilm killing assays were performed using *Staphylococcus epidermidis* 35984.
Main Results:
- All tested antibiotics released from calcium sulfate beads demonstrated antibacterial efficacy.
- Daptomycin and rifampin plus vancomycin beads maintained antimicrobial efficacy for 15 days.
- The combination of vancomycin and rifampin prevented the emergence of resistant mutants.
- All tested antibiotic combinations significantly reduced biofilm bacteria within 24 hours.
Conclusions:
- Calcium sulfate bone void fillers can effectively incorporate and release multiple antibiotics while retaining antibacterial activity.
- Specific antibiotic combinations, such as daptomycin and rifampin/vancomycin, offer sustained efficacy and resistance prevention.
- Antibiotic-eluting calcium sulfate beads show promise for treating PJIs and eradicating challenging biofilms.
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