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 pharmaceuticalgrade 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 KirbyBauer 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.

Modulating antibiotic release from reservoirs in 3D‐printed orthopedic devices to treat periprosthetic joint infection

“…These control cubes were compared to reservoirs loaded with CSH (40:1.6 g ratio of CSH:gentamicin) with one channel (0.5 mm diameter) on each vertically facing side. In agreement with previous reports, 27,28 therapeutic levels of gentamicin released over longer periods of time from CSH than PMMA ( Figure 2B). There was an initial burst release of gentamicin from PMMA in the first 24 hours with only minimal release thereafter.…”

Microencapsulation of rifampicin: A technique to preserve the mechanical properties of bone cement

“…They documented that rifampicin produced tacky black PMMA that did not harden for several days. Aiken et al studied the antimicrobial efficacy of rifampicin combined with calcium sulfate beads by a disc diffusion assay (ratio 600 mg: 20 g) against S. aureus ATCC®6538™. Zones of inhibition of bacterial growth around beads revealed that antimicrobial efficacy was unaltered after 42 days.…”

A Case Report on the Treatment of Metcillin-Resistant Staphylococcus Aureus (Mrsa) Infected Tibial Internal Fixation with Calcium

“…It provides an osteoconductive environment for vascular ingrowth. Calcium sulfate has the potential to release effective local antibiotic concentrations for a period of at least forty-two days without affecting the chemical nature and antimicrobial efficacy [11]. Results in vitro have revealed that Stimulan admixed with 10% moxifloxacin was very [12,13].…”