Elution Profiles of Synthetic CaSO4 Hemihydrate Beads Loaded with Vancomycin and Tobramycin

Abstract

Backgrounds and Objectives The use of local antibiotic delivery vehicles is common in the management of biofilm-related infections as they provide high concentrations of local antibiotics while simultaneously avoiding complications from systemic toxicity. We present a 100% pure synthetic calcium sulfate hemi-hydrate mixed with 240 mg tobramycin and 500 mg vancomycin per 10 cc mixture for use in revision surgeries of periprosthetic joint infections (PJIs). The purified carrier demonstrates bioabsorbablity, promotion of bone growth, a physiologically favorable pH, and hydrophilicity. These unique properties may alleviate persistent postoperative wound drainage seen in patients with PJI. Our questions consist of two parts: (1) does the novel calcium sulfate carrier provide therapeutic concentrations of antibiotic locally that can kill biofilm related infections? (2) Are serum concentrations of antibiotic significant to cause concern for systemic toxicity? Methods To address these questions, we assayed the elution of antibiotic concentrations obtained from surgical drains and serum among 50 patients in the first 5 postoperative days. Results The elution of vancomycin and tobramycin was greatest on day 1 compared with those concentrations obtained on days 2, 3, 4, and 5; serum concentrations were largely undetectable. Our findings demonstrate that this calcium sulfate preparation provides therapeutic delivery of vancomycin and tobramycin locally at log 2-3 above the minimum inhibitory concentration (MIC), while avoiding toxic serum concentrations. Conclusions When used in one-stage revision arthroplasties, the bioabsorbable, purified carrier delivers high concentrations of antibiotic while avoiding systemic toxicity.

The evolution from the two stage to the one stage procedure for biofilm based periprosthetic joint infections (PJI)

“…Using the Center for Biofilm Engineering (CBE) drip reactor, the calcium sulfate antibiotic loaded hemihydrate pellets destroyed all biofilm that was surface exposed [ 13 ]. A calcium sulfate pellet was beneficial in our implementation of a one-stage procedure because it was bio-absorbable, demonstrated osteoconductive potential, eliminated dead space, and delivered high concentrations of antibiotics locally without adverse systemic toxicity [ 26 ]. Compared to other variants, the carrier used was hydrophilic, possessed a physiologic pH, and was synthetically pure.…”

“…This is because the CRISPR/Cas system allows the bacteria’s immune system to recognize and destroy the foreign viral genetic material in a highly adaptable and heritable mechanism [ 19 ]. It takes to kill bacterial biofilm log 3 above the minimum inhibitory concentration (MIC) to kill the biofilm with systemic antibiotics [ 13 , 26 ]. Biofilm with systemic antibiotics kills the outer cells, but the inner, low metabolic cells persist (persister cells) [ 23 ].…”

“…These carriers can get to log 3 MIC locally without systemic levels being detected and allow for the definitive prosthesis replacement. The antibiotic loaded calcium sulfate hemihydrate with 240 ​mg of tobramycin and 500 ​mg of vancomycin per 10 ​cc completely killed Pseudomonas ERC-1, and MRSA using the Center for Biofilm Engineering (CBE) biofilm drip reactor [ 26 ]. The eluent had no viable bacteria.…”

Investigative study of the potentialities of noble applications for the Brazilian calcium sulfate α-hemihydrate

“…The peak identified exactly at 1619 cm -1 alludes to the flexion vibrations of water molecules present in the sample. Finally, it was found that the peaks located in the wave range between 1100 and 590 cm -1 are attributed to the asymmetric vibrations of the bonds of the sulfate group -SO 4 2- (Huynh et al 2020;Maale et al 2020;Zhang et al 2020).…”

Application of Calcium Sulfate for Dead Space Management in Soft Tissue: Characterisation of a Novel In Vivo Response

“…The use of CS as a material for management of residual dead space offers important advantages as it is resorbed in vivo [ 11 , 12 ] and does not require subsequent surgical removal. CS can also be combined with antibiotics to treat infections [ 13 ].…”