Aims. The aim of this investigation was to compare risk of infection in both cemented and uncemented hemiarthroplasty (HA) as well as in total hip arthroplasty (THA) following femoral neck fracture. Methods. Data collection was performed using the German Arthroplasty Registry (EPRD). In HA and THA following femoral neck fracture, fixation method was divided into cemented and uncemented prostheses and paired according to age, sex, BMI, and the Elixhauser Comorbidity Index using Mahalanobis distance matching. Results. Overall in 13,612 cases of intracapsular femoral neck fracture, 9,110 (66.9%) HAs and 4,502 (33.1%) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared with uncemented fixated prosthesis (p = 0.013). In patients with THA no statistical difference between cemented and uncemented prosthesis was registered, however after one year 2.4% of infections were detected in uncemented and 2.1% in cemented THA. In the subpopulation of HA after one year, 1.9% of infections were registered in cemented and 2.8% in uncemented HA. BMI (p = 0.001) and Elixhauser Comorbidity Index (p < 0.003) were identified as risk factors of periprosthetic joint infection (PJI), while in THA cemented prosthesis also demonstrated an increased risk within the first 30 days (hazard ratio (HR) = 2.73; p = 0.010). Conclusion. The rate of infection after intracapsular femoral neck fracture was statistically significantly reduced in patients treated by antibiotic-loaded cemented HA. Particularly for patients with multiple risk factors for the development of a PJI, the usage of antibiotic-loaded bone cement seems to be a reasonable procedure for prevention of infection. Cite this article: Bone Joint Res 2023;12(5):331–338

Objectives . The objective of this study is to determine an optimal antibiotic-loaded bone cement (ALBC) for infection prophylaxis in total joint arthroplasty (TJA). Methods. We evaluated the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with vancomycin, teicoplanin, ceftazidime, imipenem, piperacillin, gentamicin, and tobramycin against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staph. aureus (MRSA), coagulase-negative staphylococci (CoNS), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Standardised cement specimens made from 40 g PMMA loaded with 1 g antibiotics were tested for elution characteristics, antibacterial activities, and compressive strength in vitro. . Results. The ALBC containing gentamicin provided a much longer duration of antibiotic release than those containing other antibiotic. Imipenem-loading on the cement had a significant adverse effect on the compressive strength of the ALBC, which made it insufficient for use in prosthesis fixation. All of the tested antibiotics maintained their antibacterial properties after being mixed with PMMA. The gentamicin-loaded ALBC provided a broad antibacterial spectrum against all the test organisms and had the greatest duration of antibacterial activity against MSSA, CoNS, P. aeruginosa and E. coli. . Conclusion. When considering the use of ALBC as infection prophylaxis in TJA, gentamicin-loaded ALBC may be a very effective choice. Cite this article: Bone Joint Res 2013;2:220–6

Objectives. Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature. Methods. In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay. Results. The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. Conclusions. This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers. Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1

Objectives. This study is to compare the elution characteristics, antimicrobial activity, and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powder antibiotic, powder antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods. Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder, and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results. Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin–loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or xylitol group. Regarding the amphotericin B–loaded ALBCs, only the eluate samples of the liquid group exhibited a clear inhibitory zone which was not observed in either xylitol nor powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions. Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the antibiotic-release efficacy than that by loading ALBC with the same dose of antibiotic powder. This simple, and effective method for preparation of ALBCs can significantly improve the antibiotic-release efficacy of ALBCs

Aim. Galleria mellonella larvae is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections using small K-wire as implant material. Here, we aimed to further expand the use of G. mellonella to test other materials such as bone cement with combination of gentamicin to treat implant-associated infections. Method. The poly methyl methacrylate (PMMA) with and without gentamicin and liquid methyl methacrylate (MMA) were kindly provided by Heraeus Medical GmbH, Wehrheim. To make the bone cement implants as cubes, Teflon plate (Karl Lettenbauer, Erlangen) with specified well size was used. The Radiopaque polymer and monomer were mixed well in a bowl, applied over on to the Teflon plate and pressed with spatula to form fine and uniform cubes. After polymerization, the bone cement implants were taken out of the Teflon well plate with the help of pin. For the infection process, bone cement cubes were pre-incubated with S. aureus EDCC 5055 culture at 5×10. 6. CFU/ml for 30 min at 150 rpm shaking conditions. Later, these implants were washed with 10ml PBS and implanted in the larvae as mentioned. Survival of the larvae were observed at 37°C in an incubator. To analyze the susceptibility of the bacterial infections towards gentamicin, survival of the larvae compared with control group implanted only with bone cement. The effect of gentamicin was also measured in terms of S. aureus load in larvae on 2. nd. day. SEM analysis was performed to see the effect of gentamicin on biofilm formation on bone cement. Results. Our experiments established the G. mellonella as an excellent model to screen bone cement with antimicrobial compounds against bacterial infections. The gentamicin bone cement samples showed excellent S. aureus bacterial load reduction after the implantation in G. mellonella model. The bone cement with gentamicin showed better survival of larvae infected with S. aureus compared to control. Finally, the gentamicin also affected the biofilm formation on the bone cement surface with S. aureus. Conclusions. Thus, our work showed G. mellonella is a rapid, cheap economical pre-clinical model to study the bone cement associate bacterial infections as well as screening of the various antimicrobial compounds

Aim: Prosthetic loosening has emerged as a most serious long-term complication after Joint Arthroplasty and the most common cause for revision. Arthroplasty is performed either under a general anaesthesia or a spinal/ epidural or a combination of the two. During general anaesthesia Sevoßurane is used for induction and maintenance. We investigated the effect of Sevoßurane on bone cement in an in vitro setting. Materials & Methods:. 40 beads of roughly the same size were prepared from 2 mixes in a sterile condition in vacuum. 20 of these beads were scanned initially under an electron microscope at 2 levels of magniþcation. The surface images of all the cement beads were analysed. Equal numbers of scanned and unscanned beads were separated into 2 groups of 20 each. They were immersed into 2 jars of normal saline. One was connected to the anaesthetic apparatus and exposed to Sevoßurane at a concentration of 2.5%. The other group (control) was exposed to oxygen. This was performed for 2 hours in an orthopaedic theatre. All the beads were then scanned. Results & Conclusions: The post Sevoßurane exposure images revealed a large number of pits of irregular dimensions on the surface. There were no changes on the surface of control beads. This suggests that in clinical concentrations Sevoßurane can affect the surface of bone cement and its mechanical properties. This can in turn affect the bone cement interface and be a potential cause of prosthetic loosening

The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. We thank H.Y. Hsu for performing the bioassay

Primary hip and knee joint replacements in Canada have been estimated to cost over $1.4 billion dollars annually, with revision surgery costing $177 million. The most common cause of revision arthroplasty surgery in Canada is infection. Periprosthetic joint infections (PJIs) are a devastating though preventable complication following arthroplasty. Though variably used, antibiotic laden bone cement (ALBC) has been demonstrated to decrease PJIs following primary total knee arthroplasty (TKA). Unfortunately, ALBC is costlier than regular bone cement (RBC). Therefore, the aim of this study was to determine if the routine use of ALBC in primary TKA surgery is a cost-effective practice from the perspective of the Canadian healthcare system. A decision tree was constructed using a decision analysis software (TreeAge Software, Williamstown, Massachusetts) to a two-year time horizon comparing primary TKA with either ALBC or RBC from the perspective of a single-payer healthcare system. All costs were in 2020 Canadian dollars. Health utilities were in the form of quality adjusted life years (QALYs). Model inputs for cost were derived from regional and national databases. Health utilities and probability parameters were derived from the latest literature. One-way deterministic sensitivity analysis was performed on all model parameters. The primary outcome of this analysis was an incremental cost-effectiveness ratio (ICER) with a willingness-to-pay (WTP) threshold of $50,000 per QALY. Primary TKA with ALBC (TKA-ALBC) was found to be more cost-effective compared to primary TKA with RBC (TKA-RBC). More specifically, TKA-ALBC dominated TKA-RBC as it was less costly on the long term ($11,160 vs. $11,118), while providing the same QALY (1.66). The ICER of this cost-utility analysis (CUA) was $-11,049.72 per QALY, much less than the WTP threshold of $50,000 per QALY. The model was sensitive to costs of ALBC-TKA as well as the probability of PJI following ALBC-TKA and RBC-TKA. ALBC ceased to be cost effective once the cost of ALBC was greater than $223.08 CAD per bag of cement. The routine use of ALBC in primary TKA is a cost-effective practice in the context of the Canadian healthcare system as long as the cost of ALBC is maintained at a reasonable price and the published studies to-date keep supporting the efficacy of ALBC in decreasing PJI following primary TKA. Further, this analysis is very conservative, and ALBC is likely much more cost-effective than presented. This is due to this model's revision surgery cost parameter being based on the average cost of all revision TKA surgery in Canada, regardless of etiology. Considering many PJIs require two-stage revisions, the cost parameter used in this analysis for revision surgery is an underestimate of true cost. Ultimately, this is the first cost-effectiveness study evaluating this topic from the perspective of the Canadian healthcare system and can inform future national guidelines on the subject matter

Purpose of the Study. This study aims at investigating the effect of application time of bone cement on the cement-bone interface strength in two types of commercially available bone cements, Cement-A and Cement-B. Materials and methods. Cement-A and Cement-B were applied to cancellous bone specimens at two different times; 2 and 4 minutes (min). The bone specimens were formulated from bovine bone. Specimens were loaded to failure and the force at which the cement-bone interface failed was recorded. The shear strength of the cement-bone interface was calculated by dividing the force at failure by the cross-sectional surface area of the cement-bone interface. Results. The mean (± standard deviation) and median (inter-quartile range) shear strength of the cement-bone interface was 2.79 ± 1.29 MPa and 2.29 (2.34) MPa for Cement-A applied at 2 min; 1.35 ± 0.89 MPa and 1.35 (1.74) MPa for Cement-A applied at 4 min; 2.93 ± 1.21 MPa and 3.01 (2.61) MPa for Cement-B applied at 2 min; and 3.00 ± 1.11 MPa and 2.92 (1.61) MPa for Cement-B applied at 4 min. Compared to all other groups, the cement-bone interface strength was significantly lower when Cement-A was applied to the bone specimens at 4 min (p < 0.05). There was no significant difference in the cement-bone interface strength when Cement-B was applied to bone at 2 and at 4 min. Conclusions. Under these testing conditions, the cement-bone interface strength did not seem to be affected by the time of application of Cement-B to bone. However, it was significantly lower when Cement-A was applied to bone at 4 min

This study aimed to analyze the effect of two different techniques of cement application: cement on bone surface (CoB) versus cement on bone surface and implant surface (CoBaI) on the short-term effect of radiolucent lines (RLL) in primary fully cemented total knee arthroplasties (TKA) with patella resurfacing. 379 fully cemented TKAs (318 patients) were included in this monocentric study. Preoperative and postoperative at week 4 and 12 month after surgery all patients had a clinical and radiological examination and were administered the Oxford Knee Score (OKS). Cement was applied in two different ways among the two study groups: cement on bone surface (CoB group) or cement on bone surface and implant surface (CoBaI group). The evaluation of the presence of RLL or osteolysis was done as previously described using the updated Knee Society Radiographic Evaluation System. The mean OKS and range of motion improved significantly in both groups at the 4-week and 12-month follow-up, with no significant difference between the groups (CoB vs. CoBaI). RLL were present in 4.7% in the whole study population and were significantly higher in the CoBaI group (10.5%) at the 4-week follow-up. At the 12-month follow-up RLL were seen in 29.8% of the TKAs in the CoBaI group, whereas the incidence was lower in the CoB group (24.0% (n.s.)). There were two revisions in each group. None of these due to aseptic loosening. Our study indicated that the application of bone cement on bone surface only might be more beneficial than onto the bone surface and onto the implant surface as well in respect to the short-term presence of RLL in fully cemented primary TKA. The long-term results will be of interest, especially in respect to aseptic loosening and might guide future directions of bone cement applications in TKA

According to the latest report from the German Arthroplasty Registry, aseptic loosening is the primary cause of implant failure following primary hip arthroplasty. Osteolysis of the proximal femur due to the stress-shielding of the bone by the implant causes loss of fixation of the proximal femoral stem, while the distal stem remains fixed. Removing a fixed stem is a challenging process. Current removal methods rely on manual tools such as chisels, burrs, osteotomes, drills and mills, which pose the risk of bone fracture and cortical perforation. Others such as ultrasound and laser, generate temperatures that could cause thermal injury to the surrounding tissues and bone. It is crucial to develop techniques that preserve the host bone, as its quality after implant removal affects the outcome of a revision surgery. A gentler removal method based on the transcutaneous heating of the implant by induction is proposed. By reaching the glass transition temperature (T. G. ) of the periprosthetic cement, the cement is expected to soften, enabling the implant to be gently pulled out. The in-vivo environment comprises body fluids and elevated temperatures, which deteriorate the inherent mechanical properties of bone cement, including its T. G. We aimed to investigate the effect of fluid absorption on the T. G. (ASTM E2716-09) and Vicat softening temperature (VST) (ISO 306) of Palacos R cement (Heraeus Medical GmbH) when dry and after storage in Ringer's solution for up to 8 weeks. Samples stored in Ringer's solution exhibited lower T. G. and VST than those stored in air. After 8 weeks, the T. G. decreased from 95.2°C to 81.5°C in the Ringer's group, while the VST decreased from 104.4°C to 91.9°C. These findings will be useful in the ultimate goal of this project which is to design an induction-based system for implant removal. Acknowledgements: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – SFB/TRR-298-SIIRI – Project-ID 426335750

Introduction and Objective. The continued effectiveness of antibiotic loaded bone cements is threatened by antibiotic resistance. The common antiseptic, chlorhexidine (CHX), is a potential alternative to antibiotics in bone cements, but conventional salts are highly soluble, causing burst release and rapid decline to subinhibitory local CHX concentrations. Here, chlorhexidine triphosphate (CHX-TP), a low solubility CHX salt, is investigated as an alternative antimicrobial in PMMA bone cements. The aim was to assess duration of antimicrobial release and antimicrobial efficacy, along with handling, setting and mechanical properties of CHX-TP loaded cements, compared with an existing cement formulation containing gentamicin. Materials and Methods. Palacos R (Heraeus Medical, Newbury, UK) with 0, 1, 4, 7 and 12% CHX-TP (w/w) cements were prepared by combining solid CHX-TP with Palacos R components, and compared with Palacos R+G. All cements were prepared without vacuum and under ISO 5833:2002 conditions. Cements were tested under ISO 5833:2002 for compressive and bending properties, setting time, maximum temperature and doughing time. Antimicrobial release from the cements into deionised water was studied and antimicrobial efficacy of unaged and aged cements against Staphylococcus aureus (ATCC 29213) was assessed using a disc diffusion assay. Results. Compressive strength of CHX-TP loaded cements was not significantly different to Palacos R or Palacos R+G (p > 0.05, all exceeding ISO 5833:2002 minimum of 70 MPa). Mean bending strength was significantly lower with CHX-TP loading (p < 0.05) than bending strength of Palacos R and Palacos R+G, though all bending moduli exceeded the ISO 5833:2002 minimum (1800 MPa). All cements studied were within the ISO 5833:2002 limits for setting time (3 to 15 min), doughing time (≤ 5 min) and maximum temperature (90 . o. C). Mean doughing time for Palacos R, Palacos R+G and Palacos R + 12 % CHX-TP respectively: 52.5 s, 45 s and 45 s. Mean setting time and mean maximum temperature for Palacos R, Palacos R+G and Palacos R + 1, 4, 7 and 12% CHX-TP respectively: 11.00 min (73 . o. C), 11.25 min (72 . o. C), 12.25 min (66 . o. C), 10.50 min (70 . o. C), 10.00 min (70 . o. C), 10.75 min (62 . o. C). Sustained CHX release into deionised water was observed from all Palacos R + CHX-TP cements. Duration varied according to CHX-TP dosing and diminished over time, although to an extent that itself varied with dosing. 1 % CHX-TP ceased releasing CHX at 6.9 weeks; 4 % CHX-TP ceased at 67.7 weeks; 7 % and 12 % CHX-TP were ongoing at 75.5 weeks. Palacos R+G cements ceased releasing detectable levels of gentamicin after 14.4 weeks. Palacos R+G and Palacos R + CHX-TP cement discs showed efficacy against S. aureus (ATCC 29213) when applied as prepared (unaged) to S. aureus bacterial lawns in disc diffusion assays, with CHX-TP cements showing dose dependency. Zone of inhibition (ZOI) size was significantly reduced for Palacos R+G cements and Palacos R + 1% CHX-TP cements after 1 week and 6 weeks aging, compared to ZOI from unaged cements (p < 0.05). ZOI size produced by Palacos R + 4, 7, and 12 % CHX-TP cements did not decline significantly after 6 weeks aging (p > 0.05). Conclusions. CHX-TP can be incorporated into the Palacos R cement matrix up to 12% w/w without deterioration of compressive strength, bending modulus, doughing time, setting time or maximum temperature. Bending strength was significantly reduced at all CHX-TP loadings studied. Palacos R + 4, 7 and 12% CHX-TP cements provided sustained CHX release, exceeding the duration of gentamicin release from Palacos R+G, and showed sustained efficacy against S. Aureus after 6 weeks aging, which was not achieved by Palacos R+G cements

Aims. Poly(methyl methacrylate) (PMMA)-based bone cements are the industry standard in orthopaedics. PMMA cement has inherent disadvantages, which has led to the development and evaluation of a novel silorane-based biomaterial (SBB) for use as an orthopaedic cement. In this study we test both elution and mechanical properties of both PMMA and SBB, with and without antibiotic loading. Methods. For each cement (PMMA or SBB), three formulations were prepared (rifampin-added, vancomycin-added, and control) and made into pellets (6 mm × 12 mm) for testing. Antibiotic elution into phosphate-buffered saline was measured over 14 days. Compressive strength and modulus of all cement pellets were tested over 14 days. Results. The SBB cement was able to deliver rifampin over 14 days, while PMMA was unable to do so. SBB released more vancomycin overall than did PMMA. The mechanical properties of PMMA were significantly reduced upon rifampin incorporation, while there was no effect to the SBB cement. Vancomycin incorporation had no effect on the strength of either cement. Conclusion. SBB was found to be superior in terms of rifampin and vancomycin elution. Additionally, the incorporation of these antibiotics into SBB did not reduce the strength of the resultant SBB cement composite whereas rifampin substantially attenuates the strength of PMMA. Thus, SBB emerges as a potential weight-bearing alternative to PMMA for the local delivery of antibiotics. Cite this article: Bone Joint Res 2021;10(4):277–284

Background. Tigecycline, the first member of glycylcycline family, has effective antimicrobial activity against resistant and implant associated infectious organisms. The objectives of this study are to assess the compressive and tensile mechanical strength characteristics of tigecycline loaded bone cement and to compare them with vancomycin and daptomycin loaded bone cements which are used in prosthetic joint infections with resistant microorganisms. Methods. A control group without antibiotics and three antibiotic loaded bone cement groups with varying concentrations (1g, 2g and 3g vancomycin, 0.5g, 1g and 1.5g daptomycin and 50mg, 100mg and 150mg tigecycline) were prepared and tested according to ASTM F451 and ISO 5833 standards. Statistical analysis of the obtained data done by using LSD (least significant difference) and Bonferroni corrected Mann Whitney tests. Results. Both compression and tension tests showed that all determined antibiotic concentrations resulted in significant decrease when compared to the control group. Despite heterogenous statistical results, it was seen that the mechanical strength of tigecycline loaded bone cement was not significantly lower (even higher in some comparisons) when compared to vancomycin and daptomycin loaded bone cements. Conclusion. When used at defined concentrations, tigecycline loaded bone cement does not have mechanical disadvantage compared to vancomycin and daptomycin loaded bone cements. Thus, it should be kept in mind as an option in appropriate clinical situations

Objectives. The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content. Methods. Four cement groups were prepared using commercial PMMA bone cement: a control; one with 1 g of rifampin; and one each with equimolar amounts of ascorbic acid or hydroquinone relative to the amount of rifampin added. The handling properties, setting time, exothermic output, and monomer loss were measured throughout curing. The mechanical strength of each group was tested over 14 days. A radical scavenging assay was used to assess the scavenging abilities of rifampin and its individual moieties. Results. Compared with control, the rifampin-incorporated cement had a prolonged setting time and a reduction in exothermic output during polymerization. The rifampin cement showed significantly reduced strength and was below the orthopaedic weight-bearing threshold of 70 MPa. Based on the radical scavenging assay and strength tests, the hydroquinone structure within rifampin was identified as the polymerization inhibitor. Conclusion. The incorporation of rifampin into PMMA bone cement interferes with the cement’s radical polymerization. This interference is due to the hydroquinone moiety within rifampin. This combination alters the cement’s handling and curing properties, and lowers the strength below the threshold for weight-bearing applications. Additionally, the incomplete polymerization leads to increased toxic monomer output, which discourages its use even in non-weight-bearing applications. Cite this article: G. A. Funk, E. M. Menuey, K. A. Cole, T. P. Schuman, K. V. Kilway, T. E. McIff. Radical scavenging of poly(methyl methacrylate) bone cement by rifampin and clinically relevant properties of the rifampin-loaded cement. Bone Joint Res 2019;8:81–89. DOI: 10.1302/2046-3758.82.BJR-2018-0170.R2

Aim. There is an ongoing controversy whether the observed benefit of infection risk reduction by ALBC outweighs the risk of possible antimicrobial resistance development. Methods. The scientific & clinical literature in PubMed, Medline and Embase has been systematically reviewed with the keywords “antibiotic resistance”, “antibiotic loaded bone cement”, “local antibiotics”, “bacterial colonization” and “joint infection”. In total 28 relevant publications were found with the majority of them reporting laboratory results. Only 7 papers focused on clinical septic situations & patient data. Results. Although rare as consequence of the initially high drug concentrations in situ, experimental and clinical studies demonstrated survival of resistant bacteria on ALBC with subsequent bacterial re-colonisation of the biomaterial. This was most notable for coagulase-negative staphylococci (CoNS). Bacterial survival in presence of ALBC represents a selection process of already pre-existing high-level resistant mutants and not antibiotic resistance induction. The use of antibiotic combinations with gentamicin in bone cement is associated with a markedly lower risk of survival of resistant bacteria. This is particularly important in patients at high infection risks and in septic revision cases. There is no clinical evidence for a widespread increase of clinically important gentamicin resistancies in the orthopaedic ward because of routine use of ALBC. On an individual basis, the benefit of a lower infection probability with combined systemic & local antibiotic application should outweigh the risk of selecting pre-existing resistant bacteria. Each prevented infection case means that a complex and extended antibiotic therapy with risk of antibiotic resistance development over time has been avoided for a patient. In those cases where pre-existing resistant bacteria have survived the prophylactic exposure to antibiotics in bone cement, they remain in vast majority still susceptible to the clinically important antibiotics used for treatment of prosthetic joint infections. Conclusions. The benefit of a lower infection probability with ALBC should outweigh the risk of selecting resistant bacteria against the particular antibiotic used in bone cement. A trend towards broad resistance development which may complicate treatment of infection cases was not found

Polymethylmethacetate (PMMA) is a bone cement used in over 725,000 primary hip arthroplasties in 2018. Cement integrity is affected by external factors, including temperature, mixing technique and moisture uptake, which can influence cement microstructure. Changes in the cement microstructure may ultimately threaten the survivorship of the implant. The introduction of enhanced recovery and various local anaesthetic infiltration techniques have been adopted in an attempt to facilitate early mobilisation and reduce length of stay. Our study aims to investigate if the mechanical properties of PMMA are altered with exposure to Ropivacaine LA. Cements were cured in three separate states (air, serum and serum with LA) and the mechanical properties tested at 24 hours and 28 days. Using Refobacin bone cement provided by ZimmerBIOMET, cylindrical molds (12×6mm) were constructed with a split-mold. The LA used was 2mg/ml Ropivacaine hydrochloride solution. Using pilot data, this study was powered to 80% and a sample size of 10 per group (n=60) was calculated. Cement samples were subjected to compressive loading using a universal testing apparatus (Zwick/Roell). Yield-strength and modulus values were extracted from the respective stress versus strain curves. Significant differences were determined by one-way anova for each time point, and Bonferroni post-hoc testing to determine significance between actual groups. At 24-hours there were no significant differences in strength or modulus between groups. At 28-day strength and modulus increased in all groups. Compared to the air group, both serum and LA groups show a significant decrease in compressive strength. The modulus for the LA group is significantly less stiff compared to the air group. The results suggest that the initial exposure to LA has a significant impact on the physical properties of the PMMA. We propose increased awareness of the potential effects this may have on the longevity and survivorship of cemented implants

The removal of cement debris at the time of primary and revision joint replacement has been facilitated through the introduction of coloured bone cements. Up to date, few studies have evaluated the effect of methilene blue dye on physical, mechanical and pharmacological properties of cements. In this light, we evaluated the effects of adding methylene blue to bone cement with or without antibiotics (gentamicin, vancomycin or both). The addition of methylene blue to plain cement significantly decreased its mean compression (95.4±3 MPa vs 100.1±6 MPa, p = 0.03) and bending (65.2±5 MPa vs 76.6±4 MPa, p < 0.001) strengths, mean setting time (570±4 seconds vs 775±11 seconds, p = 0.01), as well as its mean elastic modulus (2744±97 MPa vs 3281±110 MPa, p < 0.001). Bending resistance decreases after the supplementation of the coloured cement with vancomycin and gentamicin (55.7±4 MPa vs 65.2±5 MPa, p < 0.001). The release of antibiotics from the bone cement was significantly decreased by the methylene blue. Indeed, the release of gentamicin alone was 385.5±26 μg in comparison to 228.2±24 μg when the methylene blue was added (p < 0.001), while the release of gentamicin in combination with vancomycin was 613±25 μg vs 498.5±70 μg (p = 0.018) when the dye was added to the same formulation. With this study we demonstrated several theoretical disadvantages of the antibiotic-loaded bone cement coloured with methylene blue, although caution should be exercised in transferring our findings to the clinical context. Based on our findings, we do not recommend methylene blue supplementation of PMMA for routine clinical use

Antibiotic-laden bone cement is an important strategy of treatment for an established bone infection. It was aimed to find the safe antibiotic dose intervals of the antibiotic cements soaked in Phosphate Buffered Saline solution and to determine whether there was a difference in terms of mechanical strength between the prepared samples. This study was done in our institute Microbiology and Metallurgy laboratories. All samples were prepared using manual mixing technique using 40 g radiopaque Biomet® Bone cement (Zimmer Biomet, Indiana, USA) under sterile conditions at 19 ± 2 ºC. In this study, vancomycin (4 groups − 0.5, 2, 4, 6 g), teicoplanin (4 groups − 0.8, 1.2, 2, 2.4 g), daptomycin (4 groups − 1, 2, 2.5, 3 g), piperacillin-tazobactam (4 groups − 0.125, 0.5, 1, 2 g) and meropenem (4 groups − 0.5, 2, 4, 6 g) were measured in a assay balance and added to the cement powder. Antibiotic levels ranged from the lowest 0.625% to the highest 15%. 80×10×4 mm rectangle prism-shaped sample for mechanical measurements in accordance to ISO 5833 standart and 12×6×1 mm disc-shaped samples for microbiological assesments were used. Four sample for each antibiotic dose and control group was made. Prepared samples were evaluated macroscopically and faulty samples were excluded from the study. Prepared samples were kept in Phosphate Buffered Saline solution renewed every 24 hours at 37 ºC. At the end of 6 weeks, all samples were tested with Instron ® 3369 (Norwood Massachusetts, USA) four point bending test. Staphylococcus aureus (ATCC 29213) strain was used for samples of antibiotics containing vancomycin, teicoplanin and daptomycin after the samples prepared for antibiotic release were maintained under sterile conditions and kept in Phosphate Buffered Saline solution as appropriate. For samples containing meropenem and piperacillin - tazobactam antibiotics, Pseudomonas aeruginosa (ATCC 27853) strain was used. The addition of more than 5% antibiotics to the cement powder was significantly reduced mechanical strength in all groups(p <0.05) however the power of significance was changed depending on the type of antibiotic. In general, adding antibiotics with 2.5% and less for cement amount was not cause significant changes in mechanical measurements. There was a negative correlation between the increase in the amount of antibiotics mixed with cement and the durability of the cement (p: <0.001, r: −0.883 to 0.914). In this study, especially the antibacterial effects of piperacillin-tazobactam, containing 0.25 gr and 0.5 gr antibiotic doses, were found to be low. There was no bacterial growth in all other groups for 21 days. Considering the mechanical properties of groups containing meropenem, vancomycin, daptomycin and teicoplanin, it was observed that all antibiotic cements remained above the limit value of 50 MPa in the bending test at concentrations containing 2.5% and less antibiotics. This was not achieved for the piperacillin-tazobactam group. The findings of the study showed that each antibiotic has different MPa values at different doses. Therefore, it could be concluded that not only the antibiotic dose but also the type oould change the mechanical properties. In the light of these findings, mixing more than 2.5% antibiotics in cement for the antibiotic types included in the study was ineffective in terms of antibacterial effect and mechanically reduces the durability of cement below the standard value of 50 MPa

We developed a novel silorane-based biomaterial (SBB) for use as an orthopedic cement. SBB is comprised of non-toxic silicon-based monomers, undergoes non-exothermic polymerization, and has weight-bearing strength required of orthopedic cements. We sought to compare the antibiotic release kinetics of this new cement to that of commercially available PMMA bone cement. We also evaluated each material's inherent propensity to support the attachment of bacteria under both static and dynamic conditions. One gram of either rifampin or vancomycin was added to 40g batches of PMMA and SBB. Pellets were individually soaked in PBS. Eluate was collected and tested daily for 14 days using HPLC. Compressive strength and modulus were tested over 21 days. Bioassays were used to confirm the bioactivity of the antibiotics eluted. We measured the growth and maturation of staphylococcus aureus (SA) biofilm on the surface of both PMMA and SBB disks over the course of 72 hours in a static well plate and in a dynamic biofilm reactor (CDC Biofilm Reactor). N=4 at 24, 48, and 72 hours. A luminescent strain of SA (Xen 29) was employed allowing imaging of bacteria on the discs. SBB eluted higher concentrations of vancomycin than did PMMA over the course of 14 days (p<0.001). A significant 55.1% greater day 1 elution was observed from SBB. Silorane cement was able to deliver rifampin in clinically favorable concentrations over 14 days. On the contrary, PMMA was unable to deliver rifampin past day 1. The incorporation of rifampin into PMMA severely reduced its mechanical strength (p<0.001) and modulus (p<0.001). Surface bacterial radiance of PMMA specimens was significantly greater than that of SBB specimens at all time points (p<0.05). The novel silorane-based cement demonstrated superior antibiotic release and, even without antibiotic incorporation, demonstrated an innate inhabitation to bacterial attachment and biofilm