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.

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.

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.

Introduction: Local drug delivery yields higher gentamicin concentrations than can be safely achieved with systemic application. Unfortunately, both for beads as well as for bone cements, a sharp drop in release follows high initial gentamicin release. Aim of this study is to compare the effects of pulsed ultrasound on the release of gentamicin from antibiotic-loaded beads and bone cements. Mercury intrusion porosimetry is carried out to compare the pore size distribution in both materials before and after antibiotic release.

Materials and Methods: Ultrasound: Gentamicin release from three brands of gentamicin-loaded bone cement (CMW 1, Palamed G and Palacos R-G) and Septopal gentamicin-loaded beads was measured after 18 h of exposure in PBS to an ultrasonic field of 46.5 kHz in a 1:3 duty cycle with a peak intensity of 500 mW/cm² at the sample position. Ultrasound experiments were performed for 18h in 9-fold on bone cement and in 6-fold on beads. Samples not exposed to ultrasound were used as controls. The gentamicin release was measured with fluorescence polarisation immunoassay. Gentamicin release from insonated and control groups was compared using a two-tailed Student’s t test for independent samples.

Mercury intrusion porosimetry: In order to mimic bone cement and beads after prolonged stay in the human body (i.e. after initial release of the loaded gentamicin) samples were immersed for four and two weeks, in PBS. Immersed and not-immersed samples were compared.

Results: Pulsed ultrasound significantly enhanced gentamicin release from gentamicin-loaded beads, whereas gentamicin release from the gentamicin-loaded bone cements was not significantly enhanced. Mercury intrusion porosimetry revealed a rise in pores between 0.1 and 0.01 um in beads after gentamicin release, while in bone cements no increase in the number of pores before and after antibiotic release was found.

Conclusions: Ultrasound increases gentamicin release from antibiotic-loaded acrylic beads by 15%. Development of pores coincides with increased gentamicin release by ultrasound for beads. Application of ultrasound could optimise usage of an (antibiotic) reservoir in local drug delivery systems to treat bone and soft tissue infections more effectively.