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

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.

Effects of storage up to 1 year on the in vitro antimicrobial activity of preformulated antibiotic‐impregnated calcium sulfate beads

“…Other methods of analysis could be pursued for further objective measurements, such as polarized fluorescent immunoassays, epsilometer test, strips or liquid chromatography-mass spectrometry, as have been previously reported. 16,34 There are notable limitations in this study. Preformulated antibiotic-impregnated beads demonstrated similar antimicrobial activity for up to 1 year, but a true shelf life was not elucidated at the conclusion of the end of the study period.…”

“…While multiple attempts to create an assay that would allow the analysis of amikacin, no meaningful data could be generated. Other methods of analysis could be pursued for further objective measurements, such as polarized fluorescent immunoassays, epsilometer test, strips or liquid chromatography‐mass spectrometry, as have been previously reported 16,34 …”

“…32 Variation in elution duration between various sizes of beads impregnated with amikacin has been described, with larger beads eluting longer but smaller beads reaching a higher peak concentration when drug concentration was measured via liquid chromatographymass spectrometry. 34 In the current study, 3.0 mm beads were used due to their ability to reliably produce consistent ZOIs when measured with a modified Kirby-Bauer assay in a preliminary study. The 3.0 mm vancomycinimpregnated CaSO 4 beads in this study produced ZOIs for approximately 10 days, whereas those with amikacin produced ZOIs for approximately 5 days, which was comparable with those previously reported.…”

“…The 3.0 mm vancomycinimpregnated CaSO 4 beads in this study produced ZOIs for approximately 10 days, whereas those with amikacin produced ZOIs for approximately 5 days, which was comparable with those previously reported. 32,34 However, direct comparison is not possible between the two studies because size, antibiotic concentration per bead, and testing methods varied.…”

“…In a previous study, larger beads (5.0 mm) eluted for a longer time (20 days) than the 3.0 mm beads (10 days) but the smaller vehicle eluted a much higher proportion of total antibiotic in the first 3 days 32 . Variation in elution duration between various sizes of beads impregnated with amikacin has been described, with larger beads eluting longer but smaller beads reaching a higher peak concentration when drug concentration was measured via liquid chromatography–mass spectrometry 34 . In the current study, 3.0 mm beads were used due to their ability to reliably produce consistent ZOIs when measured with a modified Kirby–Bauer assay in a preliminary study.…”