Bead size has a greater effect on in vitro elution from antimicrobial-impregnated calcium sulfate beads than drug concentration

Abstract

Abstract OBJECTIVE To compare the elution characteristics of amikacin-impregnated calcium sulfate (CaSO4) beads based on different drug concentrations and bead size configurations. SAMPLE Six groups of amikacin-impregnated CaSO4 beads and one negative control group. PROCEDURES Amikacin-impregnated CaSO4 beads were formed with either 500 mg (low-concentration) or 1 g (high-concentration) of amikacin per 15 g CaSO4 hemihydrate powder. The number of beads necessary to approximate 150 mg of amikacin for each of the 3 bead sizes (3 mm, 5 mm, and 7 mm) at both low and high concentrations were placed in 6 mL of phosphate-buffered saline. The saline was sampled at 14 time points over 28 days. Amikacin concentrations were determined using liquid chromatography-mass spectrometry. RESULTS Smaller beads reached higher mean peak concentrations than larger beads (P < .0006). Peak concentrations for the low- and high-concentration groups were 20.5 mg/mL and 27.4 mg/mL, 13.1 mg/mL and 14.0 mg/mL, and 8.85 mg/mL and 6.75 mg/mL for the 3 mm, 5 mm, and 7 mm beads, respectively. Bead size also affected the length of therapeutic duration, lasting 6 days for the 3 mm and 5 mm beads and 9 days for the 7 mm beads. However, this was only statistically evident among the high-concentration beads (P < .044). Antimicrobial concentration within the same bead sizes did not affect elution. CLINICAL RELEVANCE Amikacin-impregnated CaSO4 beads achieved extreme supratherapeutic eluent concentrations. While additional studies are needed, bead size significantly affected elution with smaller beads reaching higher peak concentrations and 7 mm, high-concentration beads demonstrating a longer therapeutic duration than smaller beads.