Local release of antibiotics for surgical site infection management using high-purity calcium sulfate: an in vitro elution study

Abstract

Background: The aim of this study was to characterize the elution of four antibiotics from pharmaceutical-grade calcium sulfate beads and show that the eluted antibiotics retained efficacy.

Methods: Calcium sulfate was combined with gentamicin, tobramycin, vancomycin, or rifampicin (ratio: 20 g of calcium sulfate, to 240 mg, 500 mg, 900 mg, and 600 mg of antibiotic, respectively). Three grams of beads were immersed in 4 mL of sterile phosphate-buffered saline (PBS) at 37°C. At each time point (4, 8, 24 h; 2, 7, 14, 28, 42 d), eluates were removed for analysis by liquid chromatography-mass spectrometry. The antimicrobial efficacy of antibiotics combined with calcium sulfate beads after 42 d was tested by a modified Kirby-Bauer disc diffusion assay.

Results: All samples showed a generally exponential decay in the eluted antibiotic concentration. At the first time point, both gentamicin and tobramycin had eluted to a peak concentration of approximately 10,000 mcg/mL. For rifampicin, the peak concentration occurred at 24 h, whereas for vancomycin, it occurred at 48 h. The eluted concentrations exceeded the minimum inhibitory concentration for common periprosthetic joint infection pathogens for the entire span of the 42 study days. Mass spectrometry confirmed all antibiotics were unchanged when eluted from the calcium sulfate carrier. Antimicrobial efficacy was unaltered after 42 d in combination with calcium sulfate at 37°C.

Conclusions: Pharmaceutical-grade calcium sulfate has the potential for targeted local release of tobramycin, gentamicin, vancomycin, and rifampicin over a clinically meaningful time period.

Figures

FIG. 1.

Preparation of calcium sulfate beads using flexible mold.

FIG. 2.

Concentration (mcg/mL) of gentamicin, vancomycin, tobramycin, or rifampicin determined by liquid chromatography–mass spectrometry over time in phosphate-buffered saline removed from tubes containing 3 g of 3-mm beads. Bars represent standard error of the mean.

FIG. 3.

Concentration (mcg/mL) of gentamicin, vancomycin, tobramycin, or rifampicin determined by liquid chromatography–mass spectrometry over time in phosphate-buffered saline removed from tubes containing 3 g of 6-mm beads. Bars represent standard error of the mean.