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Aims: In arthroplasty and particulary in revision surgery antibiotic-loaded bone cements are applied. The purpose of the current study was to analyse the kinetics of antibiotic release and antimicrobial effects of the gentamicin- and clindamycin-loaded bone cement Versabond., Materials and Methods: Test cylinders of bone cements, containing gentamicin and clindamycin in different concentrations, were investigated in vitro with regards to the kinetics of antibiotic release by applying static and continuous elution methods. Antimicrobial effects of antibiotic-loaded bone cement were tested in an infection model with different strains of Staphylococcus aureus and Staphylococcus epidermidis and live/dead dye plus fluorescence microscopy. For the surface analysis of antibiotic-loaded test cylinders contaminated with Staphylococcus epidermidis, scanning electron microscopy was used., Results: The measurement of static and continuous elution revealed initially higher rates of gentamicin release in comparison with clindamycin. The gentamicin amount decreased within 24 h, whereas clindamycin-loaded test cylinders showed a prolonged release. After 24 h exclusive avital bacteria on antibiotic-loaded cement cylinders were seen, after 72 h on gentamicin-loaded cement bacterial growth was again detected. Application of antibiotics in bone cement revealed an inhomogeneous surface of the bone cement cylinder., Conclusions: On application of clindamycin in bone cement the features of increased antibiotic uptake and antimicrobial effect compared with gentamicin-loaded bone cement are observed.

The in vitro release of vancomycin, teicoplanin, gentamicin and clindamycin from biodegradable calcium sulphate (CaSO(4)) carrier beads is described. All antibiotics showed prolonged release from the carrier beads, which was elevated during the first 24 h, with peak levels exceeding 2500 microg/bead. Doubling the antibiotic load of the beads revealed a more prolonged elution and a two-fold increase in antibiotic release. Local carrier-associated antibiotic treatment with CaSO(4) beads may prove to be effective in the management of chronic bone infections.

Low viscosity bone cement is expected to give improved long term fixation of prosthetic components by increased intrusion into cancellous bone. Fixation is more difficult to achieve after revision for infection because of the inferior quality of the bone. We have compared the amount of gentamicin released from high viscosity and low viscosity bone cements in 41 patients undergoing total hip replacement. The concentration of gentamicin in serum and the wound secretion, and the amount recovered from the urine, was about three times higher for low viscosity cement. A possible explanation for this is an increase in surface area of the cement body because of improved intrusion of cement into bone. The improved mechanical fixation and the high concentration of gentamicin of the bone cement interface favours the use of low viscosity cement, especially in revision for deep infection.

Comparing several antibiotics and different bone cements, the mixture of Palacos R (polymethylmethacrylate, PMMA) with gentamicin proved to be the most suitable one as far as a high and sustained release of the antibiotic from the artificial resin is concerned. A continuous leaching of gentamicin was observed for more than 5 years. Gentamicin proved to be stable in Palacos R for the whole period of time. The release of 12 antibiotics from Palacos R was evaluated in vitro. Four other bone cements were included in this study as well, in order to evaluate the leaching of gentamicin from these materials. The combination Gentamicin-Palacos R (GP) showed a 2--3 fold higher and much more prolonged release than did the other mixtures. From this investigation, which also included studies of commercially available antibiotic bone cement mixtures, it is quite obvious that there exist distinct differences in the various bone cements as well as in the various antibiotics as regards their qualification for use in alloarthroplasty. Pharmacokinetic studies in patients after implantation of GP showed low gentamicin concentrations in serum (on average 1.8 microgram/ml) and urine. However, in wound exudate, derived directly from the vicinity of the implanted cement, gentamicin concentrations up to 150 micrograms/ml were observed. Also in tissue samples from the vicinity of the implant, high concentrations were measurable for a long period of time (up to 5 1/2 years).

A randomised, double-blind study was performed in two groups of 15 patients undergoing total hip replacements, using antibiotic-loaded acrylic cement containing 0.5 g and 1.0 g gentamicin base respectively per 40 g pack of powdered polymer. Postoperatively, the gentamicin levels in the blood, in the urine and in the wound drainage fluid were measured. In both groups of patients, the serum gentamicin concentrations were low whereas the wound drainage fluid contained highly effective antibacterial concentrations. Serum, urine and wound secretion levels showed approximately two-fold higher concentrations in the group of patients receiving the higher gentamicin load.

Gentamicin PMMA beads (PMMA = polymethylmethacrylate) represent a new form of local antibiotic therapy for treating chronic bone and soft tissue infections. Gentamicin is released in high concentrations from PMMA. The therapeutic efficacy of the beads was demonstrated in a model of bone infection in dogs. Sufficiently high tissue concentrations of gentamicin were measurable for a period of 4 months. A very good tolerance of the beads was demonstrated in dogs as well as in cell cultures. High gentamicin concentrations exceeding the MBC values of relevant pathogens were measurable in patients at the site of infection. Serum and urine concentrations were low and therefore toxic side effects are excluded.

Authors describe a new method of treatment for bone and soft tissue infections using polymethyl methacrylate balls containing Gentamycin. Advantages of this method can be summarized in 3 points: 1. From the patients point of view saving the rinsing-sucking drainage, early mobilisation etc. 2. From nursing point of view a significant facilitation of the patient's care. 3. From the hospital management's point of view: improved hygienic conditions by eliminating the possible infections related to a rinsing-sucking wet system. Cutting down hospital expences both by abbreviation of the time of hospitalization and saving on expensive antibiotics.

Gentamicin incorporated in beads of polymethylmethacrylate has been shown capable of being released over a period of several months in concentrations sufficiently high to control most pathogens. The therapeutic efficacy of such beads has been demonstrated in a model of osteomyelitis of the femur in the dog. Good tolerance has been shown, both in the animal model and in tissue cultures. In forty-one patients with infection of either bone or soft tissue, mainly of the lower limb, the findings were similar. The concentrations in serum and urine were low, which excludes side-effects. The insertion of gentamicin-PMMA beads may prove to be a valuable new form of local antibiotic therapy.