Search Results (15)

Background: The use of antibiotic-loaded bone cements (ALBCs) in arthroplasty has been well established for the prevention and treatment of infections. Tigecycline (Tig), a broad-spectrum antibiotic, has shown efficacy against various pathogens, including vancomycin-resistant strains. Method: ISO and DIN mechanical and microbiological inhibition zone tests were performed on PMMA cement with manually added Tigecycline. Results: Manually adding 0.5 and 1.0 g Tigecycline to PMMA always meets the mechanical requirements of ISO and DIN standards. Mixtures containing 0.5 g were microbiologically effective for up to 7 days and those containing 1.0 g were effective for 28–42 days. Conclusion: In revision surgery, manually adding Tigecycline in doses of 0.5–1 g to 40 g of PMMA is effective against MRSA, VRE, and ESBL without negatively affecting the cement’s properties. Full article

The increasing numbers of total joint replacements and related implant-associated infections demand solutions, which can provide a high-dose local delivery of antibiotics. Antibiotic-loaded bone cement (ALBC) is an accepted treatment method for infected joint arthroplasties. The mechanical properties of low-dose gentamicin-loaded bone cement (BC) in medium- and high-viscosity versions were compared to unloaded BC using a vacuum mixing system. As an additional control group, manual mixed unloaded BC was used. In a uniaxial compression test, ultimate compressive strength, compressive yield strength, and compression modulus of elasticity, as well as ultimate and yield strain, were determined according to ISO 5833-2022 guidelines. All groups exceeded the minimum compressive strength (70 MPa) specified in the ISO 5833 guidelines. Both ALBC groups showed a similar ultimate compressive and yield strength to the unloaded BC. The results showed that vacuum mixing increased the compression strength of BC. ALBC showed similar compressive strength to their non-antibiotic counterparts when vacuum mixing was performed. Added low-dose gentamicin acted as a plasticizer on bone cement. From a biomechanical point of view, the usage of gentamicin-based ALBC formulations is viable. Full article

Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and antimicrobial efficacy of antimicrobial coatings and compounds. Here, we aim to utilize Galleria mellonella implant infection models to assess the antimicrobial activity of antibiotic-loaded bone cement (ALBC) implants. Therefore, we used commercially available bone cement loaded with either gentamicin alone (PALACOS R+G) or with a combination of gentamicin and vancomycin (COPAL G+V), compared to bone cement without antibiotics (PALACOS R). Firstly, the in vitro antimicrobial activity of ALBC was determined against Staphylococcus aureus. Next, the efficacy of ALBC implants was analyzed in both the G. mellonella hematogenous and early-stage biofilm implant infection model, by monitoring the survival of larvae over time. After 24 h, the number of bacteria on the implant surface and in the tissue was determined. Larvae receiving dual-loaded COPAL G+V implants showed higher survival rates compared to implants loaded with only gentamicin (PALACOS R+G) and the control implants without antibiotics (PALACOS R). In conclusion, G. mellonella larvae infection models with antibiotic-loaded bone cements are an excellent option to study (novel) antimicrobial approaches. Full article

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10–147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment. Full article

Background: The number of periprosthetic joint infections caused by vancomycin-resistant pathogens is increasing. Currently, no PMMA cement is commercially available to cover VRE. Daptomycin shows promising results in treating infection, offering a good safety profile and a reduced risk of developing resistance. The purpose of this in vitro study was to investigate the mechanical stability, handling properties, elution behavior, and antimicrobial effectiveness of PMMA cement loaded with three different daptomycin concentrations in comparison to commercially available antibiotic-loaded bone cement (ALBC). Methods: Mechanical properties and handling characteristics (ISO 5833, DIN 53435), HPLC elution, antimicrobial effectiveness with proliferation assay (DIN 17025), and inhibition zone testing were investigated. Results: All tested daptomycin concentrations met the ISO and DIN standards for mechanical strength. Loading of 40 g of PMMA cement with 0.5 g of daptomycin did not show any antimicrobial effectiveness, in contrast to 1.0 g and 1.5 g. PMMA cement with 1.5 g of daptomycin was the best in terms of elution and effectiveness, and it showed good ISO mechanical strength; ISO doughing was sticky for a little longer and setting was faster compared to the vancomycin-containing reference cement. Conclusion: PMMA cement containing 0.5 g of gentamicin and 1.5 g of daptomycin could be a good alternative to the already established COPAL^® (Wehrheim, Germany) G+V for the treatment of PJIs caused by VRE. Full article

Antibiotic-loaded bone cement (ALBC) has become an indispensable material in orthopedic surgery in recent decades, owing to the possibility of drugs delivery to the surgical site. It is applied for both infection prophylaxis (e.g., in primary joint arthroplasty) and infection treatment (e.g., in periprosthetic infection). However, the introduction of antibiotic to the polymer matrix diminishes the mechanical strength of the latter. Moreover, the majority of the loaded antibiotic remains embedded in polymer and does not participate in drug elution. Incorporation of the various additives to ALBC can help to overcome these issues. In this paper, four different natural micro/nanoscale materials (halloysite, nanocrystalline cellulose, micro- and nanofibrillated cellulose) were tested as additives to commercial Simplex P bone cement preloaded with vancomycin. The influence of all four materials on the polymerization process was comprehensively studied, including the investigation of the maximum temperature of polymerization, setting time, and monomer leaching. The introduction of the natural additives led to a considerable enhancement of drug elution and microhardness in the composite bone cements compared to ALBC. The best combination of the polymerization rate, monomer leaching, antibiotic release, and microhardness was observed for the sample containing nanofibrillated cellulose (NFC). Full article

Background: Antibiotic-loaded bone cement (ALBC) spacers are used in the first stage when treating periprosthetic joint infection (PJI). This study aimed to investigate whether a spacer made from commercial ALBC or plain bone cement with additional antibiotics could affect the spacer exchange rate before reimplantation. Methods: Patients undergoing two-stage exchange arthroplasty due to chronic PJI from January 2014 to August 2021 were retrospectively reviewed. The exclusion criteria included arthroplasty in the setting of septic arthritis, megaprosthesis, atypical pathogen infection, spacer placement unrelated to PJI, and spacer exchange due to mechanical complications. The patient demographics, brand of cement, and microbiology were recorded manually. The primary outcome was the incidence of spacer exchange due to persistent infection and the secondary outcome was the incidence of reinfection after reimplantation. A multivariate logistic regression analysis and Chi-square test were conducted to identify the effect of cement type on the spacer exchange. Results: A total of 334 patients underwent two-stage exchange arthroplasty for PJI. The spacer exchange rates in the commercial and non-commercial ALBC groups were 6.4% and 25.1%, respectively (p = 0.004). After controlling for confounding factors, there were significant differences between the commercial group and non-commercial groups in the spacer exchange rate (adjusted OR = 0.25; 95% CI = 0.72–0.87, p = 0.029). The use of commercial ALBC was not associated with a lower reinfection rate after reimplantation (p = 0.160). Conclusions: In a two-stage exchange arthroplasty scenario, the spacer comprised of commercial ALBC resulted in a lower spacer exchange rate than the plain bone cement, both of which had additional antibiotics. However, the use of commercial ALBC was not associated with a lower incidence of reinfection following reimplantation. Full article

Orthopedic-device-related infection is one of the most severe complications in orthopedic surgery. To reduce the associated morbidity and healthcare costs, new prevention and treatment modalities are continuously under development. Preclinical in vivo models serve as a control point prior to clinical implementation. This study presents a mouse model of subcutaneously implanted titanium discs, infected with Staphylococcus aureus, to fill a gap in the early-stage testing of antimicrobial biomaterials. Firstly, three different inocula were administered either pre-adhered to the implant or pipetted on top of it following implantation to test their ability to reliably create an infection. Secondly, the efficacy of low-dose (25 mg/kg) and high-dose (250 mg/kg) cefazolin administered systemically in infection prevention was assessed. Lastly, titanium implants were replaced by antibiotic-loaded bone cement (ALBC) discs to investigate the efficacy of local antibiotics in infection prevention. The efficacy in infection prevention of the low-dose perioperative antibiotic prophylaxis (PAP) depended on both the inoculum and inoculation method. Bacterial counts were significantly lower in animals receiving the high dose of PAP. ALBC discs with or without the additional PAP proved highly effective in infection prevention and provide a suitable positive control to test other prevention strategies. Full article

A series of studies were conducted to demonstrate the feasibility of low-temperature bonding by the forming and heating an Al-8wt%Si alloy thick film on a B₄C surface by cold spraying. The results show that: (1) The cracks near the joining interface are closed by the Al alloy by the process studied in this study, and a joining strength of about 220 and 240 MPa is achieved by low temperature joining of 580 °C and 600 °C, respectively.; (2) The amount of weak intermetallic compounds at the joining interface is reduced; (3) It is assumed that the reduction in the amount of Al-B-C compounds is due to the formation of the β phase during the solidification process of the Al-Si alloy, which hinders the growth of the compounds.; (4) On the primary joint surface, a continuous void group is formed in the vicinity of the β phase that surrounds the α phase, causing a decrease in the joining strength. Full article

This literature review discusses the use of antibiotic loaded polymethylmethacrylate bone cements in arthroplasty. The clinically relevant differences that have to be considered when antibiotic loaded bone cements (ALBC) are used either for long-term implant fixation or as spacers for the treatment of periprosthetic joint infections are outlined. In this context, in vitro findings for antibiotic elution and material properties are summarized and transferred to clinical use. Full article

Prosthetic joint infections (PJIs) ensued from total joint replacement (TJR) pose a severe threat to patients that involve poor health outcomes, severe pain, death (in severe cases), and negative influence patients’ quality of life. Antibiotic-loaded bone cement (ALBC) is frequently used for the prevention and treatment of PJI. This work aims to study gentamicin release from carbon nanotubes (CNTs) incorporated in polymethyl methacrylate (PMMA) bone cement to prolong release over several weeks to provide prophylaxis from PJIs after surgery. Different CNT concentrations were tested with the presence of gentamicin as a powder or preloaded onto carboxyl functionalized CNTs. The different types of bone cement were tested for drug release, mechanical properties, water uptake, antimicrobial properties, and cytocompatibility with human osteoblast cells (MTT, LDH, alizarin red, and morphology). Results showed prolonged release of gentamicin from CNT-loaded bone cements over several weeks compared to gentamicin-containing bone cement. Additionally, the presence of CNT enhanced the percentage of gentamicin released without adversely affecting the nanocomposite mechanical and antimicrobial properties needed for performance. Cytotoxicity testing showed non-inferior performance of the CNT-containing bone cement to the equivalent powder containing cement. Therefore, the developed nanocomposites may serve as a novel PMMA bone cement to prevent PJIs. Full article

Gram-negative bacilli can be responsible for prosthetic joint infection (PJI) even if staphylococci are the main involved pathogens. Gram-negative PJIs (GN-PJI) are considered difficult-to-treat infections due to the increase in antimicrobial resistance and biofilm formation. To minimize the risk of infection in cases of arthroplasties with cemented prosthesis, bone cement can be loaded with antibiotics, especially gentamicin. In this study, we aimed to compare the prophylactic antibiofilm activity of ready-to-use antibiotic-loaded bone cements (ALBC), already commercialized or new prototypes. We compared ALBCs containing gentamicin alone, gentamicin plus vancomycin, gentamicin plus clindamycin, gentamicin plus Fosfomycin, and fosfomycin alone, to plain cement (no antibiotic); these comparisons were conducted to investigate the biofilm formation of three strains of Escherichia coli, three strains of Pseudomonas aeruginosa and two strains of Klebsiella pneumoniae, with or without specific resistance to gentamicin or fosfomycin. We reported that ALBC containing gentamicin and clindamycin (COPAL G+C) seems to be the most interesting ALBC of our tested panel for the prevention of biofilm formation by gentamicin-susceptible strains, even if clindamycin is not effective against Gram-negative bacteria. However, gentamicin-resistant strains are still a problem, and further studies are needed to identify an antibiotic to associate with gentamicin for an efficient dual ALBC against Gram-negative bacteria. Full article

Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement with considerable morbidity and large economic burdens. Antibiotic-Loaded Bone Cement (ALBC) has been developed as a valuable tool for local administration and is becoming one of the most effective methods for the prevention and treatment of orthopedic infections. Controlling antibiotic release from ALBC is critical to achieve effective infection control, however, the antibiotic elution rates are generally low, and the mechanisms are poorly understood. Thus, the present study aims to investigate the effects of the basic acrylic bone cement components, including liquid/powder (monomer-to-polymer) ratios, radiopacifier, initiator, and doses of antibiotics on the porosity, antibiotic elution rates and mechanical properties of polymethylmethacrylate (PMMA) based ALBC. The obtained results from the in vitro studies suggested that a reduction in the liquid/powder ratio and an increase in the radiopacifier ratio and gentamicin doses led to increased porosity and release of antibiotic, while the initiator ratio exerted no effect on elution rates. In conclusion, we hope that by varying the composition of ALBC, we could considerably enhance the antibiotic elution rates by increasing porosity, while maintaining an adequate mechanical strength of the bone cements. This finding might provide insights into controlling antibiotic release from ALBC to achieve effective infection control after total joint replacement surgery. Full article

This paper presents a Ku-band fractional-N frequency synthesizer with adaptive loop bandwidth control (ALBC) to speed up the lock settling process and meanwhile ensure better phase noise and spur performance. The theoretical analysis and circuits implementation are discussed in detail. Other key modules of the frequency synthesizer such as broadband voltage-controlled oscillator (VCO) with auto frequency calibration (AFC) and programable frequency divider/charge pump/loop filter are designed for integrity and flexible configuration. The proposed frequency synthesizer is fabricated in 0.13 $\mathsf{\mu }$m CMOS technology occupying 1.14 × 1.18 mm${}^2$ area including ESD/IOs and pads, and the area of the ALBC is only 55 × 76 $\mathsf{\mu }$m${}^2$. The out frequency can cover from 11.37 GHz to 14.8 GHz with a frequency tuning range (FTR) of 26.2%. The phase noise is −112.5 dBc/Hz @ 1 MHz and −122.4 dBc/Hz @ 3 MHz at 13 GHz carrier frequency. Thanks to the proposed ALBC, the lock-time can be shortened by about 30% from about 36 $\mathsf{\mu }$s to 24 $\mathsf{\mu }$s. The chip area and power consumption of the proposed ALBC technology are slight, but the beneficial effect is significant. Full article

Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo. Full article