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

Abstract

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. 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°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°C. Antibiotic elution was determined with use of high-performance liquid chromatography with mass spectrometry. 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. 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. Amikacin and meropenem show pharmacologic promise as potential acceptable alternatives for local delivery in PMMA for treatment of orthopaedic infections. Further work to establish clinical relevance and utility is needed.