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

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

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

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

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

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

Aim. The demonstration of the in vivo bactericidal efficacy of a new bone cement with rifampicin contained in microcapsules and its intra-articular release profile. Method. Fifteen New Zealand White rabbits were employed to reproduce periprosthetic infection by intra-articular inoculation of 10. 5. CFU/mL of Staphylococcus aureus ATCC® 29213 using as a target implant a 3D printed stainless steel tibial insert. 7 days after inoculation, the first stage of the two stage exchange was carried out and at this time the animals were divided into two study groups: group C (7 rabbits) that received a spacer with gentamicin and group R (8 rabbits) that received a spacer with gentamicin and rifampicin microcapsules. Response to infection was monitored by clinical (weight and temperature), hematological (leukocyte, lymphocyte and platelet counts) and biochemical (erythrocyte sedimentation rate) analyses at the time of inoculation, at the first stage of exchange, 4 days after first stage and weekly until the fourth week when animals were euthanized. Microbiological counts were performed at the first stage of exchange and at the end of the study. Results. 14/15 animals (93.3%) developed a PJI 1 week after the inoculation. A statistically significant elevation of the leukocyte and platelet count and a decrease in the percentage of lymphocytes (p=0.0001) was found and positive microbiological cultures. Four weeks after the placement of the spacer, no bacterial growth was found in the soft tissue or bone samples of the group with rifampicin microcapsules (group R), being these differences statistically significant with p=0.01 and 0.03 respectively. The rifampicin intra-articular release kinetics showed concentrations above the staphylococcal MIC at all time points. Conclusions. The bone cement with microencapsulated rifampicin is effective in the in vivo treatment of prosthetic joint infection due to biofilm-forming S. aureus

Total joint arthroplasty (TJA) is one of the most successful procedures in orthopaedics. Despite the excellent clinical and functional results, periprosthetic joint infection (PJI) following TJA is a feared complication. For instance, the reported PJI rate after primary total knee arthroplasty is about 0.5–1.9%. In general, prevention of periprosthetic joint and surgical site infections is of utmost importance. This can be reduced by strict antisepsis, adequate sterilization of the surgical instruments and meticulous surgical technique. An indisputable role in prevention of SSI in TJA has been the use of peri-operative systemic antibiotic prophylaxis. The most common recommended antibiotics for prophylaxis in TJA are cefazolin or cefuroxime. In contrast, routine use of commercial antibiotic-loaded bone cement (ALBC) in primary total joint arthroplasty is still a concern of open debate. The use of antibiotic-loaded bone cement delivers a high concentration of antibiotics locally and can decrease the infection rate, which is supported by several studies in the literature. In this context, we present the pros of routine use of commercial antibiotic-loaded bone cement

Great strides have been made in the early detection and treatment of cancer which is resulting in improved survivability and more Canadians living with cancer. Approximately 80% of primary breast, lung, and prostate cancers metastasize to the spine. Poly-methyl methacrylate (PMMA) bone cement is one of the most commonly used bone substitutes in spine surgery. In clinical practice it can be loaded with various drugs, such as antibiotics or chemotheraputic drugs, as a means of local drug delivery. However, studies have shown that drugs loaded into PMMA cement tend to release in small bursts in the first 48–72 hours, and the remaining drug is trapped without any significant release over time. The objective of this study is to develop a nanoparticle-functionalized PMMA cement for use as a sustained doxorubicin delivery device. We hypothesize that PMMA cement containing mesoporous silica nanoparticles will release more doxorubicin than regular PMMA. High viscosity SmartSet ™ PMMA cement by DePuy Synthes was used in this study. The experimental group consisted of 3 replicates each containing 0.24 g of mesoporous silica nanoparticles, 1.76 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The control group consisted 3 replicates each containing 2.0 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The experimental group contained an average of 8.18 ± 0.008 % (W/W) mesoporous silica nanoparticles. Each replicate was casted into a cylindrical block and incubated in a PBS solution which was changed at predetermined intervals for 45 days. The concentration of eluted doxorubicin in each solution was measured using a florescent plate reader. The mechanical properties of cement were assessed by unconfined compression testing. The effect of the doxorubicin released from cement on prostate and breast tumor cell metabolic activity was assessed using the Alamar Blue test. After 45 days the experimental group released 3.24 ± 0.25 % of the initially loaded doxorubicin which was more than the 2.12 ± 0.005% released by the control group (p 0.03). There was no statistically significant difference in Young's elasticity modulus between groups (p 0.53). Nanoparticle functionalized PMMA suppressed the metabolic activity of prostate cancer by more than 50 percent but did not reach statistical significance. Nanoparticle functionalized PMMA suppressed the metabolic activity of breast cancer cells by 69 % (p < 0.05). Nanoparticle-functionalized PMMA cement can release up to 1.53 times more doxorubicin than the standard PMMA. The use of mesoporous silica nanoparticles to improve drug release from PMMA cement shows promise. In the future, in vivo experiments are required to test the efficacy of released doxorubicin on tumor cell growth

Despite the prophylactic use of antibiotics and hygienic strategies, surgical site infection following total joint arthroplasty (TJA) is still a severe and unsolved complication. Since antibiotic-loaded bone cement (ALBC) was introduced by Buchholz in the 1970s, the use of ALBC has been increasingly used for the prevention and treatment of periprosthetic infection (PPI). However, the routine use of ALBC during primary TJA remains controversial. Recent clinical studies have found that ALBC is effective in reducing the risk of PJI following primary TJA. Although ALBC having the advantage of reducing the risk of PJI, the main disadvantages are the possible development of toxicity, antibiotic resistance, allergic reaction, and possible reduction of the mechanical properties of bone cement. Nevertheless, a recent published article demonstrated, that the use of high dose dual-antibiotic impregnated cement reduce significantly the rate of surgical site infections compared to standard low dose single ALBC in the setting of a hip fracture treating with hemiarthroplasty. Furthermore, Sanz-Ruiz et al. presented that the use of ALBC in TJA has favorable cost-efficiency profile. In this context, reasons why surgeons should use antibiotic-loaded bone cement during primary TJA are demonstrated

Introduction. The use of antibiotic-loaded polymethylmethacrylate bone-cement spacers during two-stage exchange procedures is the standard in the treatment of patients with delayed prosthetic joint infection. The real antimicrobial activity of these spacers is unclear because the adherence of bacteria to cement might result in clinical recurrence of infection. The purpose of the study is to evaluate the in vitro formation of Pseudomonas Aeruginosa (PA) and Staphylococcus spp. biofilm on antibiotic-loaded bone cement. Materials and methods. Cement disks (diameter = 6 mm) impregnated with gentamicin and colistin were submerged in bacterial suspensions of Methicillin-resistant Staphylococcus Aureus(MRSA), Staphylococcus epidermidis (SE), and PA. Negative controls (specimen disks without antibiotic) were similarly prepared. Biofilm formation was visualized by confocal scanning laser microscopy (CSLM), after staining the discs with the live/dead BacLight viability stain containing SYTO 9 dye and propidium iodide. Images from five randomly selected areas were acquired for each disc. Sequential optical sections of 2 µm were collected in sequence along the z-axis over the complete thickness of the sample. The resulting stacks of images were analyzed, quantified and rendered into three-dimensional (3D). The biofilm thickness on antibiotic bone cement compared with the controls was automatically evaluated. Results. CSLM showed living bacteria and bacterial biofilm on the surface of all cement disks, either antibiotic-loaded or controls. Mean biofilm thickness on the controls was 29.6 µm for MRSA, 32.3 µm for SE, and 59.7 µm for PA. The 3D rendering showed decrease in the biofilm thickness for all bacterial strains on gentamicin- and colistin-impragnated cement disks as compared with the controls. The incorporation of gentamicin into cement resulted in a 54%, 74%, and 45% reduction in the bacterial biofilm thickness for MRSA, PA and SE, respectively. The use of colistin leaded to a 51 % reduction in the PA biofilm thickness. Conclusion. The bacterial viability and biofilm formation are reduced by adding antibiotics to bone cement but antibiotic-loaded bone cement does not completely inhibit the formation of an infectious biofilm in vitro

Aim. The aim of this investigation was to compare risk of infection in both cemented and cementless hemiarthroplasty (HA) as well as 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 cementless protheses and paired according to age, sex, body mass index (BMI), and the Elixhauser score using Mahalanobis distance matching. Results. Overall in 13,612 cases of intracapsular femoral neck fracture, with 9,110 (66.9 %) HAs and 4502 (33.1 %) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared to cementless fixated prosthesis (p=0.013). In patients with THA no statistical difference between cemented and cementless prothesis was registered, however after one year 2.4 % of infections were detected in cementless 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 cementless HA. BMI (p=0.001) and Elixhauser-Comorbidity-Score (p<0.003) were identified as risk factors of PJI, while in THA also cemented prosthesis demonstrated within the first 30 days an increased risk (HR=2.728; p=0.010). Conclusion. The rate of infection after intracapsular femoral neck fracture was significantly reduced in patients treated by antibiotic-loaded cemented hemiarthroplasty. In particular 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

Despite the demonstrated success in revision total joint arthroplasties, the utilization of antibiotic-loaded bone cement in primary total joint arthroplasty remains controversial. Multiple studies have demonstrated several risks associated with the routine use of this technique including: allergic reactions, changing the mechanical properties of the cement, emergence of resistant bacterial strains, systemic toxicity, and the added cost. In addition, evidence shows a currently low rate of periprosthetic joint infections in primary total joint arthroplasty (around 1%) and the theoretical benefit of marginally reducing this rate by using antibiotic-cement may not necessarily justify the associated risks and the added cost. Moreover, most of the primary total hip and an increasing number of primary total knee arthroplasties are cementless, which further raises questions about the routine use of antibiotic-loaded bone cement in primary total joint arthroplasty

The use of antibiotic-loaded cement has become a well-accepted method to develop high local antibiotic concentrations in orthopedic surgery. A new surgical technique has been established in our department in order to further increase the local antibiotic concentration, when implanting a prosthesis during revision surgery. By additional superficial vancomycin coating of the bone cement, high local antibiotic concentrations are generated. They should reach inhibiting and bactericidal concentrations of the respective pathogen during the first days after surgery. The aim of this study was to state the safety of this method by analyzing postoperative serum and drain vancomycin concentrations. Attention was focused on possible systemic side effects. To determine nephrotoxicity, creatinine levels were also measured. In total 32 revision operations (hip n=10, knee n=22) with additional superficial vancomycin coating were performed between 05/2013 and 04/2015. Procedures with removal of the prosthesis following temporary spacer implantation were excluded. In nine cases a one-stage procedure was performed, while in the others an arthroplasty or arthrodesis was performed after temporary spacer explantation. Vancomycin powder (2 grams) was added superficially to the surface of the bone cement and pressed onto manually before curing. Postoperative Vancomycin levels were measured in serum and the drain on day 1 to 5 or until the drain has been removed. In total 90 blood serum samples and 100 drain fluid samples were obtained. The highest median vancomycin level from the drain was documented on postoperative day 1 with a value of 555.3 μg/mL (range 66.1 – 1081.8), continually decreasing until postoperative day 4. The highest value was documented on the second postoperative day with 2170.0 μg/mL. On the first postoperative day, a median serum vancomycin level of 3.35 μg/mL was present (range <2.0 – 8.5), while from postoperative day 2 to 5 a median level less than 2.0 μg/mL (range <2.0 – 7.2) was documented. Anaphylactic reaction, red man syndrome or fever and chills were not observed after the surgical procedure. Furthermore, no subjective hearing loss was reported. Only in one case, a creatinine increase of 0.5 mg/dL from baseline value was detected. In this case the patient suffered preoperatively from a chronic kidney insufficiency. In total two reinfections occurred, one after explanting a spacer with subsequent hip total endoprosthesis, the other one after a one-stage hip revision. Superficial Vancomycin Coating of bone cement in orthopedic revision surgery represents a safe method to increase local inhibiting vancomycin concentrations

Introduction. We have investigated middle-term clinical results of total hip arthroplasty (THA) cemented socket with improved technique using hydroxyapatite (HA) granules. IBBC (interfacial bioactive bone cement method, Oonishi) (1) is an excellent technique for augmenting cement-bone fixation in the long term. However, the technique is difficult and there are concerns over some points, such as bleeding control, disturbance of cement intrusion to anchoring holes by granules, difficulty of the uniform granular dispersion to the acetabular bone. To improve the original technique, we have modified IBBC (M-IBBC), and investigated the middle-term clinical results and radiographic changes. Materials and Methods. K-MAX HS-3 THA (Kyocera, Japan), with tapered cemented stem with small collar and all polyethylene cemented socket, was used for THA implants (Fig.1). Basically the third generation cementing technique was used for THA using bone cement. The socket fixation was performed with bone cement (Endurance, DePuy) and HA granules (Ca10(PO4)6(OH)2, Boneceram P; G-2, 0.3–0.6mm in size, Olympus, Japan) (Fig.2). In original IBBC technique, HA granules were dispersed on reamed acetabulum before cementing. In M-IBBC technique, HA granules were attached to bone cement on plastic plate, then inserted to reamed acetabulum and pressurized (Fig.3). 112 hip joints (95 cases) were operated between June 2010 and March 2014, and followed. The average follow-up period was 6.5 years, and average age at operation was 66.5 years. The clinical results were evaluated by Japan Orthopaedic Association Hip Score (JOA score), and X-p findings were evaluated using antero-posterior radiographs. The locations of radiolucent lines were identified according to the zones described by Delee and Charnley for acetabular components, and Zone 1 was divided into two parts, outer Zone 1a and inner Zone 1b. Results and Discussion. Revision was not performed. JOA score improved from 47 to 88. Socket and stem loosening was not observed. X-p findings of sockets demonstrated radiolucent line in Zone 1a/1b/2/3 in 0.9/0/0/0% immediately after the operation, 6.3/1.8/0/0.9% at 2 years postoperatively. After 2 years there was no progressive change, however, improvement of radiolucent line in Zone 1a was observed in two cases after 3 years postoperatively. Accordingly, at 5 years radiolucent line in Zone 1a/1b was observed in 4.4/1.8%. Oonish has reported excellent clinical results of THA with IBBC (1). To easily perform IBBC, we have modified the technique, improving the problems of IBBC. In this study, radiolucent line was observed at the margin of the socket in a small number of cases, and there was no progressive change. In addition, improvement of radiolucent line was observed in M-IBBC in this study, which was not observed in conventional cementing technique. Conclusions. It is demonstrated that M-IBBC provides stable socket cement fixation for THA. The interesting finding in M-IBBC cases was the improvement of radiolucent line, suggesting osteoconductive property of hydroxyapatite granules at the interface after the operations. The promising long-term clinical results of M-IBBC method, were expected. For any figures or tables, please contact the authors directly

Periprosthetic infection after total joint replacement is a catastrophic complication. Current rates of infection have been decreasing and in most centers now are in the range of 0.1–1%. Peri-operative intravenous antibiotic therapy is used routinely in total hip arthroplasty patients at this time. With rates this low and mixed evidence that antibiotics in bone cement for routine total hip replacement are beneficial at reducing joint infection, routine use of this practice seems unnecessary and has potential disadvantages. Cost of antibiotics being added to cement on a routine basis will increase the cost of the arthroplasty $300–$500. Although small addition of bone cement also has a negative effect on the mechanical properties of the cement. The major disadvantage remains the danger of resistant bacterial strains from excessive use of antibiotics particularly vancomycin resistant organisms when it is used routinely. Although rare with the aminoglycosides, allergic reactions may occur if cephalosporins are used as prophylaxis. Use of antibiotics in bone cement should be considered in high risk patients for infection undergoing total hip replacement but not routinely because of cost, emergence of resistant organism and possible allergic reaction

Acrylic bone cements are used rather extensively in orthopedic and spinal applications. The incorporation of calcium phosphate additives to bone cements, to induce osteoconductivity, have typically resulted in increased cement viscosity, decreased handling, and detrimental effects of the mechanical performance of the cement. Additionally, bioactive bone cements are offered at a premium cost, which limits clinical use of these materials. The goal of this study was to examine and characterize an alternative two-solution poly (methyl Methacrylate) (PMMA) bone cement (referred to as TSBC), after incorporation of several calcium phosphate additives and antimicrobials. These bioactive and antimicrobial two-solution cements were designed to have adjustable properties that meet specific requirements of orthopedic applications. The addition of a bioactive agent would lead to increased levels of bone reformation after surgery, while an antibiotic within the cement would decrease the ability for pathogens to grow in the interface between the bone and new implant. TSBC is a pre-mixed bone cement that exhibits a combination of attractive properties including high strength, adjustable viscosity, adequate exothermal properties, as well as offering the possibility of using the same batch multiple times. The addition of antibiotics has not been previously explored in two-solution bone cements. Therefore, it is desirable to induce antibacterial activity with this formulation. Hydroxyapatite (Ca5(PO4)3(OH)), Brushite (CaHPO4•2H2O), and Tricalcium Phosphate (Ca3(PO4)2)(TCP) were incorporated into the TSBC in varying concentrations (25 and 50 wt%), and the rheological characteristics were examined to verify the feasibility of adding high concentrations of fillers to this cement formulation. Results demonstrated that unlike commercial powder-liquid formulations, calcium phosphate additives in TSBC do not detrimentally affect handling and the rheological properties of the material, while also providing maintenance of cement strength and other physical properties. TSBC material spends a dramatically increased amount of time in the swelling phase, as compared to powder-liquid formulations and thus is better suited to incorporate additives fully into its polymer matrix. Current two-solution bone cements do not contain any osteoconductive or antimicrobial agents. This study investigated the effects of addition of these bioactive agents in the physical and mechanical properties of the cement. Cement porosity was investigated to ensure that the porous nature of the bioactive cement does not damage the mechanical stability of the material. Further imaging will be conducted to demonstrate the improved osteointegration of these bioactive cement with osteoblasts (Figure 1). Degradation studies have been conducted to validate the biodegradable properties of the bioactive components and antibiotics release profile. It is further hypothesized that the degradation time will correlate to the antimicrobial activity. As the cement is replaced with natural bone, more and more antimicrobial will become exposed to the physiologic environment causing a continuous antimicrobial release as the material is partially replaced with new bone over time. Antimicrobial effectiveness and antimicrobial release studies are under-way to illustrate the cements ability to restrict growth at the cement surface, as well as show the antimicrobial release profile over time

In two-stage revision surgery of infected joint prosthesis, temporary bone cement spacers have been used for several years. By adding antibiotics to the cement, high local antibiotic concentrations that exceed the minimum inhibiting and bactericidal concentration of the respective pathogen during the first days after surgery, are achieved. Currently, aminoglycosides (e.g. gentamicin and tobramycin), as well as glycopetides (e.g vancomycin) are used as antibiotic agents and mixed into the acrylic cement. In order to increase the quantity of active antibiotic substances, we established a novel surgical technique of additional superficial vancomycin coating (SVC) of temporary bone cement spacer. The aim of this study was to analyze the safety of this method by measuring postoperative joint and serum vancomycin concentrations, as well as the creatinine levels. We reviewed prospectively collected data on all patients, which were treated by explanting the prosthetic components, following temporary spacer implantation and SVC between 05/2013 and 04/2015 at the Department of Orthopedic Surgery, Medical University of Graz. In total 13 patients were treated by addition SVC during the study period. Before hardening, vancomycin powder (2 grams) was pressed manually onto the surface of the bone cement. Vancomycin levels were obtained from drains and blood samples on postoperative days 1 to 5. Forty-six blood serum samples and 52 drain fluid samples were available for further. On postoperative day one to five, a median serum vancomycin level of < 2.0 μg/mL was present (range <2.0 – 3.9). The highest median vancomycin level from the drain was documented on postoperative day 1 with a value of 388.0 μg/mL (range 44.4–1650.0), continually decreasing until postoperative day 4. After SVC, neither an anaphylactic reaction nor side effects such as a red man syndrome, fever and chills were observed. Furthermore, no patient complained about subjective hearing loss. No serum creatinine increase of 0.5 mg/dL from creatinine baseline value or a ≥50% increase from baseline was detected. After a median of 64 days (range 18–82), the temporary cement spacer was explanted followed by prosthesis implantation. During this time no reinfection occurred. One patient suffered from a dislocation of the spacer with a distal femur fracture and was therefore re-operated after 18 days. Powdered vancomycin as an additional superficial coating of bone cement spacer results in much higher local antibiotic concentrations than in conventional spacers. The newly introduced method is feasible, safe and promising to enhance local inhibiting concentrations of vancomycin