Amikacin & meropenem impregnated calcium sulfate beads effective for orthopaedic infections

New York, USA: The study by LEVACK et al provides important novel data regarding the utility of amikacin, meropenem and dalbavancin as alternative choices to place in CaSO4 carriers when treating orthopaedic infections.

The presence of sessile bacteria within biofilm exhibit alternative resistance mechanisms compared to similar bacteria in planktonic form. The challenges of treating biofilms clinically is an area of ongoing research. Investigating alternative local delivery mechanisms could permit surgeons to broaden the list of antibiotics available for treatment.

There has been increasing interest in the use of a synthetic absorbable calcium sulfate (CaSO4) for local antibiotic delivery in orthopaedic infections.

LEVACK et al conducted a study to quantify elution kinetics of six antibiotics (amikacin, meropenem, fosfomycin, minocycline, cefazolin, and dalbavancin) from a clinically relevant CaSO4 bead model and compare elution and antimicrobial activity to the current clinical gold standards: vancomycin and tobramycin.

The antibiotics amikacin, meropenem, fosfomycin, and minocycline are active against resistant bacteria and are used clinically in difficult to treat gram‐negative infections; cefazolin is effective against methicillin‐sensitive gram‐positive pathogens; and dalbavancin is a novel lipoglycopeptide that has remarkable efficacy against methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant enterococcus while being less nephrotoxic and hepatotoxic than vancomycin.

Antibiotic‐loaded synthetic CaSO4 beads were immersed in phosphate buffered saline and incubated at 37°C. Eluent was harvested at eight time points over 28 days. Antibiotic concentrations were measured by high performance liquid chromatography to quantify elution rates. CaSO4 beads demonstrated burst release kinetics.

Dalbavancin, cefazolin, and minocycline all demonstrated similar elution profiles to vancomycin.

Amikacin and meropenem demonstrated favorable elution profiles and durations of above‐ minimum inhibitory concentration when compared to tobramycin.

The authors concluded that - this study provides important novel data regarding the utility of amikacin, meropenem and dalbavancin as alternative choices to place in CaSO4 carriers when treating orthopaedic infections.

The conditions set here for identifying antibiotic suitability when using CaSO4 carriers highlights the need for surgeons to learn more about how elution patterns and elution rates differ among antibiotics, and that taking an individualized approach to antibiotic choice and carrier is needed if orthopaedic infection cure rates are to improve.

This study does not inform the clinical efficacy of these antibiotics for clinical infections or in the setting of sessile bacteria within biofilms. Future studies using in vivo models are needed to provide a better understanding of both the kinetics of antibiotic elution from calcium sulfate and the activity of alternative antibiotics against both planktonic and sessile bacteria.

Further reading:

Identifying alternative antibiotics that elute from calcium sulfate beads for treatment of orthopedic infections.

Ashley E. Levack et al

The Journal of Orthopedic Research

DOI: 10.1002/jor.25135