Research into biocompatibility and cytotoxicity of daptomycin, gentamicin, vancomycin and teicoplanin antibiotics at common doses added to bone cement

Abstract

Objectives: This study aims to investigate the biocompatibility and cytotoxicity of daptomycin, gentamicin, vancomycin and teicoplanin at commonly-used dose intervals added to polymethylmethacrylate (PMMA) in vitro.

Materials and methods: This prospective study was conducted between February 2016 and June 2016. Antibiotics were added to PMMA at doses frequently used in clinical practice. The antibiotic doses added were teicoplanin (2 g, 3 g, 4 g), gentamicin (0.5 g, 0.75 g, 1 g), daptomycin (0.5 g.) and vancomycin (2 g, 3 g, 4 g). Standard cement balls (10 mm) were created. Activated L929 mouse fibroblast cell culture was used for incubation. Agar diffusion, Cell Proliferation Kit II (XTT) test and electron microscope investigations were performed to examine biocompatibility and cytotoxicity.

Results: In the cytotoxicity test, teicoplanin at 4 g and daptomycin at 0.5 g doses were observed to cause reductions in viability percentages. The same doses caused 20% and 20-40% cell lysis indices during the agar diffusion test. On electron microscope images, cytotoxic effects in fibroblast cells and involvement with the surface of cement balls were observed.

Conclusion: Gentamicin, vancomycin and teicoplanin were observed to be non-toxic and biocompatible at commonly-used dose intervals. Teicoplanin at 4 g and daptomycin at 0.5 g doses were identified to be cytotoxic and not biocompatible. When selecting antibiotics to be added to bone cement, care should be taken that the antibiotic is non-toxic and biocompatible.

Figure 1. Preparation of standard 10x10 mm bone cement samples.

Figure 2. Standard samples at 10 mm diameter with different doses of antibiotics added.

Figure 3. Samples prepared for agar diffusion test by placement in center of medium.

Figure 4. Scanning electron microscope image showing cytotoxic effect of daptomycin antibiotic at 0.5 g dose on fibroblasts (LEO 440 computer-controlled digital, Cambridge, England). Bone cement was of an intensified layered polymethylmethacrylate structure which was polymerized, and antibiotic particles were seen to exhibit regular distribution in a spherical morphology. Blue arrows show that fibroblasts still tend to grow in presence of antibiotic, but this had caused cell death by showing a toxic effect regionally.