Background and purpose: Commercial gentamicin-loaded bone cement beads (Septopal^®) constitute an effective delivery system for local antibiotic therapy. However, these beads are not commercially available in all parts of the world, and are too expensive for common use in others. Therefore, orthopedic surgeons worldwide make antibiotic-loaded beads themselves. However, these beads are usually not as effective as the commercial beads because of inadequate release kinetics. The aim of this study was to develop a simple, cheap and effective formulation to prepare gentamicin-loaded beads with release properties and antibacterial efficacy similar to the ones of commercially available beads.

Methods: Acrylic beads were first prepared with variable monomer contents: 500 μl/g polymer (100%), 375 μl/g polymer (75%), and 250 μl/g polymer (50%) to increase gentamicin release through the creation of a less dense polymer matrix. After optimal monomer content was defined, different gel-forming polymeric fillers were added to enhance the permeation of fluids into the beads. Polyvinylpyrrolidone (PVP) 17 was selected as a suitable filler, its concentration was varied and the antibiotic release and antibacterial efficacy of the final beads were compared with the ones of Septopal^® beads.

Results: Gentamicin release rate and extend of release from beads prepared with 50% monomer increased upon increasing the PVP 17 content in the beads. Beads with 15 w/w% PVP 17 released 87% of their antibiotic content within 336 h. Importantly, this is significantly more than the gentamicin-release from Septopal^® beads, that appeared confined to only 59% within 336 h. In addition, acrylic beads with 15 w/w% PVP 17 reduced bacterial growth up to 93%, which is a similar reduction as achieved with Septopal^®.

Interpretation: A simple, cheap and effective formulation and preparation process has been described for hand-made gentamicin-releasing acrylic beads, with release kinetics and antibacterial efficacy similar to the ones of commercially available Septopal^® beads.

Background and Purpose: The remarkably low wear of metal-on-metal (MOM) bearings involving cobalt-chromium (Co-Cr) alloys has led to a resurgence in its use. However, consequences of these wear particles and the corrosion products are for the most part unclear. Recent research efforts towards the bacteriological influences of the MOM-degradation products suggested that particulate MOM debris promotes planktonic bacterial growth. On the other hand, extremely high concentrations of metal ions, derived from salts, have shown to possess bacteriostatic effects (growth reduction) on planktonic growth and on biofilm formation. The effects of salt-derived metal ions were found to be inhibitory and not bactericidal (lethal to bacteria). However, these two findings were both found under static growth conditions and no studies have investigated these findings under more clinically resembling dynamic growth conditions. In addition, influences of Co-Cr particles on biofilm formation have not yet been studied. Therefore, the aim of this study was to evaluate how Co-Cr particles and Co-Cr ions affect biofilm formation under static and dynamic growth conditions.

Methods: A collection of clinically isolated bacterial strains were exposed to Co-Cr particles and Co-Cr ions in concentrations as found in serum and above as found in adjacent tissue. The experiments were conducted as well under static, as under dynamic growth conditions. Biofilm formation in wells, stained with live/dead viability staining and visualized by confocal laser scanning microscopy, was analyzed with COMSTAT, yielding biovolume, biofilm thickness, and live/dead ratio of the bacteria within the biofilm.

Results: Co-Cr particle concentrations of 20 g/L reduced biofilm formation significantly. Moreover, these particle concentrations were found to be bactericidal (killed the bacteria). The live/dead ratio decreased when culturing was done under dynamic growth conditions when compared to the static growth condition. Under both growth conditions, biofilm formation was inhibited at concentrations of 10/5 mg/L Co-Cr ions, as reported to occur in synovial fluids. Co-Cr ion concentrations up to 1/0,5 mg/L revealed no consistent influence on biofilm formation.

Interpretation: Long-term clinical data on infection rates for Co-Cr MOM-bearings are not yet available, but the current results suggest that Co-Cr ions may yield these prostheses less prone to biofilm formation and subsequent infection.

Introduction: Infection is a challenging problem in orthopaedic surgery. In oncologic and revision surgery large prosthesis are placed during long procedures, even in patients with immunocompromised status. Infection rates here are reported up to 10%. Infections may necessitate large segmental resections thereby creating large defects. This defect can be filled with antibiotics loaded beads that release the substances locally to sterilise the defect. In recent years solid antibiotic loaded bone cement spacers have been applied. These spacers fill the defect, stabilize the extremity, release antibiotics and keep the soft tissues on their original length. Additionally, the patients will be able to preserve mobile function as well. In small defects prefabricated bone cement spacers temporarily replace the infected hip or knee prosthesis. For larger segmental of terminal defects there are no readily available constructs.

Purpose: To report short term outcome of a newly developed customized spacer concept for treatment of large segmental resections after prosthetic infection or osteomyelitis.

Material and Methods: We have treated 13 patients with large segmental defects after infection treatment with customized antibiotic bone cement spacers reinforced with strong intra-medullar implants like the Gammanail, the DFN and the UHN.

Results: These customized spacers are easy to make, fill the defect, stabilize the extremity, release antibiotics, keep the length of the soft tissues and allow patients to practice and preserve joint function as well. In 11 of 13 patients operated with an interim construct like this, a successful reimplantation of a tumor prosthesis was performed.

Conclusion: With customized antibiotic bone cement spacers augmented with a solid implant one can fill the defect, stabilize the extremity, release antibiotics and keep the soft tissues on their original length and keep function as well in infected tumorprosthesis. Successful reimplantation could be performed in 11 of 13 cases.

Copal bone cement loaded with gentamicin and clindamicin was developed recently as a response to the emerging occurrence of gentamicin-resistant strains in periprothetic infections. The objective of this study was to compare the in vitro antibiotic release and antimicrobial efficacy of gentamicin/clindamicin-loaded Copal bone cement and gentamicin-loaded Palacos R-G bone cement, as well as biofilm formation on these cements.

In order to determine antibiotic release, cement blocks were placed in phosphate buffer and aliquots were taken at designated times for measurement of antibiotic release. In addition, the bone cement discs were pressed on agar to study the effects of antibiotic release on bacterial growth. Biofilm formation on the different bone cements was also investigated after 1 and 7 days using plate counting and confocal laser scanning microscopy (CLSM). Experiments were done with a gentamicin-sensitive S. aureus and a gentamicin-resistant CNS.

Antibiotic release after 672 h from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Plate counting and CLSM of biofilms grown on the bone cements showed that antibiotic release reduced bacterial viability, most notably close to the cement surface. Moreover, the gentamicin-sensitive S. aureus formed gentamicin-resistant small colony variants on Palacos R-G, and therefore, Copal was much more effective in decreasing biofilm formation than Palacos R-G.

Biofilm formation on bone cement could be more effectively reduced by incorporation of a second antibiotic, next to gentamicin. Antibiotic release from the cements had a stronger effect on bacteria close to the cement than on bacteria at the outer surface of the bio-film. Clinically, bone cement with two antibiotics may be more effective than cement loaded with only gentamicin. The clinical efficacy of antibiotic loaded bone cements in combination with systemic antibiotics can be explained because antibiotics released from cements kill predominantly the bacteria in the bottom of the biofilm, whereas systemic antibiotics can only deal with bacteria at the outer surface of the biofilm.

Addition of antibiotics to the bone cement decreases the incidence of infection. However, the antibiotic is only partially released. Ultrasound may increase the antibiotic release and furthermore the effectiveness of the antibiotic might be enhanced by the so-called bio-acoustic effect.

The objective of this study was twofold. The first aim was to evaluate to what extent antibiotic release from bone cement could be increased by ultrasound. The second aim was to investigate the viability of bacteria when antibiotic release from bone cements was combined with ultrasound.

Cylindrical bone cement samples of Palacos R-G (loaded with gentamicin) and Copal (loaded with gentamicin and clindamycin) were insonated and antibiotic release was compared with uninsonated samples. In addition, identical samples were used in combination with cultures of bacteria derived from prosthesis-related infections. The viability of these bacteria was determined with and without ultrasound, using unloaded Palacos R as a control.

There was a trend of increased gentamicin release under influence of ultrasound. Clindamycin release from Copal was significantly increased. Ultrasound alone did not affect bacterial viability, but the application of ultrasound in combination with antibiotic-loaded bone cements reduced both planktonic and biofilm bacterial viability.

The release of antibiotics from bone cement was increased by the application of ultrasound. Antibiotic release in combination with ultrasound increases the antimicrobial efficacy against a variety of clinical isolates. The enhanced efficacy against bacteria in the biofilm mode of growth, especially against a gentamicin-resistant strain, is clinically important with regard to the treatment of infected joint prostheses. Ultrasound may also be applied in the early postoperative period to prevent infections, because planktonic bacteria present in the wound and wound area due to inevitable contamination during surgery can then be more effectively prevented from forming a biofilm.

Clinical experience indicates the beneficial effects of antibiotic-loaded bone cement. Although in vitro studies have shown the formation of a biofilm on its surface they have not considered the gap between the cement and the bone. We have investigated bacterial survival in that gap. Samples with gaps 200 μm wide were made of different bone cements. These were stored dry (‘pre-elution’) or submersed in phosphate-buffered saline to simulate the initial release of gentamicin (‘post-elution’). The gaps were subsequently inoculated with bacteria, which had been isolated from infected orthopaedic prostheses and assessed for their sensitivity to gentamicin. Bacterial survival was measured 24 hours after inoculation. All the strains survived in plain cements. In the pre-elution gentamicin-loaded cements only the most gentamicin-resistant strain, CN5115, survived, but in post-elution samples more strains did so, depending on the cement tested. Although high concentrations of gentamicin were demonstrated in the gaps only the gentamicin-sensitive strains were killed. This could explain the increased prevalence of gentamicin-resistant infections which are seen clinically.