Gentamicin release from commercially-available gentamicin-loaded PMMA bone cements in a prosthesis-related interfacial gap model and their antibacterial efficacy

Abstract

Background: Around about 1970, a gentamicin-loaded poly (methylmethacrylate) (PMMA) bone cement brand (Refobacin Palacos R) was introduced to control infection in joint arthroplasties. In 2005, this brand was replaced by two gentamicin-loaded follow-up brands, Refobacin Bone Cement R and Palacos R + G. In addition, another gentamicin-loaded cement brand, SmartSet GHV, was introduced in Europe in 2003. In the present study, we investigated differences in gentamicin release and the antibacterial efficacy of the eluent between these four cement brands.

Methods: 200 μm-wide gaps were made in samples of each cement and filled with buffer in order to measure the gentamicin release. Release kinetics were related to bone cement powder particle characteristics and wettabilities of the cement surfaces. Gaps were also inoculated with bacteria isolated from infected prostheses for 24 h and their survival determined. Gentamicin release and bacterial survival were statistically analysed using the Student's t-test.

Results: All three Palacos variants showed equal burst releases but each of the successor Palacos cements showed significantly higher sustained releases. SmartSet GHV showed a significantly higher burst release, while its sustained release was comparable with original Palacos. A gentamicin-sensitive bacterium did not survive in the high gentamicin concentrations in the interfacial gaps, while a gentamicin-resistant strain did, regardless of the type of cement used. Survival was independent of the level of burst release by the bone cement.

Conclusions: Although marketed as the original gentamicin-loaded Palacos cement, orthopaedic surgeons should be aware that the successor cements do not appear to have the same release characteristics as the original one. Overall, high gentamicin concentrations were reached inside our prosthesis-related interfacial gap model. These concentrations may be expected to effectively decontaminate the prosthesis-related interfacial gap directly after implantation, provided that these bacteria are sensitive for gentamicin.

Figure 1

Schematic presentation of gentamicin release into the filled gap with the possibility of further diffusion into the bulk fluid. The outer surface of the sample block was effectively covered by nail varnish (indicated by the pink color) to prevent gentamicin elution from other surfaces than the gap.

Figure 2

SEM micrographs of the Refobacin Palacos R, Refobacin Bone Cement R, Palacos R + G, and SmartSet GHV powder. The arrow indicates agglomerates of the smaller radiopacifier particles. Bar denotes 100 μm.

Figure 3

SEM micrographs of the fractured surface of cured specimens of Palacos R + G and SmartSet GHV bone cement. Note the difference in gentamicin particle shape, indicated by arrows.

Figure 4

Powder particle size distributions of the Refobacin Palacos R, Refobacin Bone Cement R, Palacos R + G, and SmartSet GHV powder.

Figure 5

Gentamicin concentration as a function of time of exposure to 6 μL of phosphate-buffered saline in a gap. The values are expressed as mean of three separate experiments, error bar denotes the average standard deviation.

Figure 6

Gentamicin concentration as a function of time of exposure of a gap to 10 mL of phosphate buffered saline. The values are expressed as mean of three separate experiments, error bar denotes the average standard deviation.