Thermal Stability and in Vitro Elution Kinetics of Alternative Antibiotics in Polymethylmethacrylate (PMMA) Bone Cement

Background: Amikacin, meropenem, minocycline, and fosfomycin have potential clinical utility for orthopaedic infections; however, their suitability for use in polymethylmethacrylate (PMMA) is poorly understood. The purpose of this study was (1) to quantify the thermal stability of these antibiotics at clinically relevant temperatures and (2) to determine the elution pharmacodynamics of these alternative antibiotics in vitro from PMMA beads of different sizes. Methods: Polymerization temperatures of 10-mm PMMA beads were measured over time to generate a simulated heating curve. Aqueous solutions of tobramycin, amikacin, meropenem, minocycline, and fosfomycin were subjected to the temperature curves, followed by incubation at 37 degrees C. Minimum inhibitory concentrations of each antibiotic were evaluated against Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii. High-dose 4.5-mm, 6-mm, and 10-mm antibiotic-laden PMMA beads (10% antibiotic by weight) were submerged individually in a phosphate-buffered saline solution and incubated at 37 degrees C. Antibiotic elution was determined with use of high-performance liquid chromatography with mass spectrometry. Results: Tobramycin, amikacin, and fosfomycin demonstrated thermal stability and maintained antimicrobial activity for 28 days. Minocycline and meropenem lost antimicrobial activity against all 3 organisms after 48 hours and 7 days, respectively. Elution concentrations, rates, and cumulative drug mass for tobramycin, amikacin, and meropenem were orders of magnitude higher than minocycline and fosfomycin at each time point. Conclusions: This study identified notable differences in thermal stability and elution among antibiotics used to treat infections. Amikacin exhibited activity similarly to tobramycin. Meropenem demonstrated favorable elution kinetics and thermal stability in the initial 7-day period.

Automated summary

This study revealed significant differences in thermal stability and elution among antibiotics used for treating infections, with amikacin showing activity similar to tobramycin, and meropenem demonstrating favorable elution kinetics and thermal stability in the initial 7-day period.