Elution profiles of tobramycin and vancomycin from high-purity calcium sulphate beads incubated in a range of simulated body fluids

Abstract

The aim of this study was to characterise the elution profiles of antibiotics in combination with pharmaceutical grade calcium sulphate beads in phosphate buffered saline and other physiological solutions which more closely mimic the in vivo environment. Synthetic recrystallised calcium sulphate was combined with vancomycin hydrochloride powder and tobramycin sulphate solution and the paste was formed into 3 mm diameter hemispherical beads. Then 2 g of beads were immersed in 2 ml of either phosphate buffered saline, Dulbecco's Modified Eagle Medium or Hartmann's solution and incubated at 37℃ for up to 21 days. At a range of time points, eluent was removed for analysis by liquid chromatography-mass spectrometry (LC-MS). Tobramycin sulphate and vancomycin hydrochloride release was successfully quantified against standard curves from solutions eluted in all three physiological media (phosphate buffered saline, Dulbecco's Modified Eagle Medium and Hartmann's solution) during incubation with calcium sulphate beads. One hour eluate concentrations were high, up to 2602 µg/ml for tobramycin in phosphate buffered saline and 7417 µg/ml for vancomycin, whereas in DMEM, the levels of tobramycin were 2458 µg/ml and 4401 µg/ml for vancomycin. The levels in HRT were 2354 µg/ml for tobramycin and 5948 µg/ml for vancomycin. The results show highest levels of antibiotic elution over the first 24 h, which gradually diminish over the following 21 days.

The Use of Calcium Sulphate beads in Periprosthetic Joint Infection, a systematic review

“…Currently, CS beads are used as an alternative void filler to PMMA in the presence of infection, non-union or bone loss (11). As it is absorbed, CS releases 100% of its antibiotic load, resulting in superior elution characteristics and higher sustained antibiotic concentrations over a period of several weeks (12). This results in concentrations of antibiotic locally that can be many times higher than the minimum inhibitory concentration for the relevant pathogen, while also ensuring that systemic levels and associated toxicity remain low (13,14).…”

Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty

“… 5 , 7 In contrast, as it is absorbed, calcium sulphate releases 100% of its antibiotic load, resulting in superior elution characteristics and higher sustained antibiotic concentrations over a period of several weeks. 5 , 7 - 10 This results in concentrations of antibiotic locally that can be many times higher than the minimum inhibitory concentration for the relevant pathogen, while also ensuring that systemic levels and associated toxicity remain low. 8 , 11 The use of calcium sulphate in orthopaedics has therefore been increasing, both as a bone void filler and as an “off-label” delivery agent for antibiotics in arthroplasty, chronic osteomyelitis, open fractures and combat injuries.…”

Single-stage treatment of chronic localized tibial osteomyelitis with local debridement and antibiotic-loaded calcium sulfate implantation：a retrospective study of 42 patients.

“…The main difference is the replacement of temporary antibiotic-impregnated PMMA beads or autologous tissues grafts by biodegradable antibiotic-impregnated calcium sulfate, which undoubtedly has its unique advantages. Primarily, the predictable high local antibiotic concentration (hundreds to thousands times higher than MIC in first 24h to 48h) and comparatively long therapeutic duration (several weeks to months) [5,17,18] provided by the degrading antibiotic-loaded calcium sulfate undoubtedly eliminates more residual pathogens while significantly shortens the conventional duration of systemic antibiotics administration. Moreover, similar to PMMA, the well-reported osteo-conductivity of calcium sulfate provides a crystalline structure for the osteoblasts perivascular mesenchymal tissues and osteoprogenitors, along which osteoblasts and the others crawl easily and eventually achieve the self-repair without autogenous bone grafts [19,20].…”