Antibiotic-loaded Bone Cement Research Articles

Antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management for sternal infection after midline sternotomy

IntroductionDeep sternal wound infection (DSWI) after midline sternotomy of cardiac surgery is a challenging complication that affects the outcome of surgery. This study aims to assess the clinical effectiveness of the antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management in the treatment of DSWI.MethodsWe retrospectively analyzed 5 patients with DSWI who underwent antibiotic-loaded bone cement combined with bilateral pectoralis major muscle flaps for chest wall reconstruction after sternotomy for cardiac surgery in a tertiary hospital in China from January 2020 to December 2021. The clinical and follow-up data were retrospectively analyzed.ResultsAll patients had no perioperative mortalities, no postoperative complications, 100% wound healing, and an average hospital stay length of 24 days. The follow-up periods were from 6 to 35 months (mean 19.6 months). None of the cases showed wound problems after initial reconstruction using antibiotic-loaded bone cement combined with bilateral pectoralis major muscle flaps.ConclusionsWe report our successful treatment of DSWI, using antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management. The clinical and follow-up results are favorable.

Combining antibiotic-loaded bone cement-based free vastus lateralis muscle-sparing flap with split-thickness skin grafts: A reliable strategy for reconstructing diabetic foot ulcers at non-weight-bearing areas.

Diabetic foot ulcers (DFUs) present significant challenges due to their associated amputation rates, mortality, treatment complexity and excessive costs. Our earlier work introduced a wound surgical integrated treatment (WSIT) for DFUs, yielding promising outcomes. This study focuses on a specific WSIT protocol employing antibiotic-loaded bone cement (ALBC) in the first Stage, and free vastus lateralis muscle-sparing (VLMS) flaps and split-thickness skin grafts (STSGs) in the second stage to repair non-weight-bearing DFUs. From July 2021 to July 2023, seven DFU patients (aged 47-71 years) underwent this treatment. Demographic data, hospital stay and repair surgery times were collected. Histological and immunohistochemical analyses assessed angiogenesis, collagen deposition and inflammation. SF-36 questionnaire measured pre- and postoperative quality of life. Preoperative ultrasound Doppler showed that the peak blood flow velocity of the recipient area artery was significantly >30 cm/s (38.6 ± 6.8 cm/s) in all patients. Muscle flap sizes varied from 8 × 3.5 × 1 to 18 × 6 × 2 cm. The operation time of the repair surgery was 156.9 ± 15.08 minutes, and the hospital stay was 18.9 ± 3.3 days. Histological analysis proved that covering DFUs with ALBC induced membrane formation and increased collagen, neovascularization and M2 macrophages fraction while reducing M1 macrophages one. All grafts survived without amputation during a 7- to 24-month follow-up, during which SF-36 scores significantly improved. A combination of ALBC with free VLMS flaps and STSGs proved to be safe and effective for reconstructing non-weight-bearing DFUs. It rapidly controlled infection, enhanced life quality and foot function, and reduced hospitalization time. We advocate integrating this strategy into DFU treatment plans.

The addition of silicon nitride to PMMA bone cements reduces bacterial attachment while supporting preosteoblast viability

Injectable poly (methyl methacrylate) (PMMA) bone cements are widely used in orthopaedics to stabilize fractures and for implant fixation. However, bacterial attachment to bone cements leads to significant complications that can create a need for implant revision. Common attempts at reducing bacterial attachment are through the addition of antibiotics or antibacterial nanometals to the bone cements. However, clinical data is inconclusive on the effectiveness of antibiotic-loaded bone cements and a negative osteoblastic response has been reported for certain additive concentrations. There is therefore a need for an additive that can positively affect osteoblastic behaviour while inhibiting bacterial attachment. Silicon nitride (Si3N4) could be such an additive, with initial studies showing promise in achieving antipathogenic properties. The aim of this study was hence to investigate the possibility of creating a bone cement that can support osteoblast growth while reducing bacterial attachment by introducing silicon nitride powders into an injectable PMMA cement. To this end, commercially available bone cements were doped with 5%, 10% and 20% weight/weight (w/w) of Si3N4. Their mechanical properties were examined through compression testing and their radiopacity was evaluated through fluoroscopy imaging. The samples that fulfilled compressive strength requirements had their biological properties tested using Staphylococcus epidermidis bacteria for antibacterial properties and MC3T3-E1 preosteoblasts for the examination of cytotoxicity. Bone cements that were doped with up to 20% w/w Si3N4 were radiopaque (only 13% reduction in optical density compared to radiopaque controls) and retained their compressive strength (85.35 ± 2.1 MPa compared to 83.4 ± 1.9 MPa for the commercial cements), while significantly reducing bacterial attachment by more than 90% compared to commercial cements and achieving a similar level of preosteoblast metabolic activity. This study supports further evaluation of Si3N4 as an additive to injectable bone cements as a way to create mechanically stable, radiopaque, bacteriostatic bone cements that could improve osteointegration.

Investigating the in vitro antibacterial efficacy of composite bone cement incorporating natural product-based monomers and gentamicin

ObjectiveThe objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC).MethodsBased on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials.ResultsThe combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05).ConclusionIn this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.

A systematic review and meta-analysis of antibiotic-loaded bone cement for prevention of deep surgical site infections following primary total joint replacement

BackgroundThe use of antibiotic-loaded bone cement (ALBC) as a mean for preventing deep surgical site infections (SSI) after total joint replacement is controversial. Therefore, we have conducted a meta-analysis to evaluate the prophylactic effect of ALBC for SSI prevention in patients undergoing arthroplasty. This study was conducted to revise treatment guidelines for MRSA infections in Japan. MethodsPubMed (Medline), Scopus, Embase, Web of Science and Cochrane library were searched for relevant articles comparing preventive effect of ALBC for patients undergoing primary total joint arthroplasty by August 2022. Primary outcome was the incidence of deep SSI. Subgroup analyses by type of surgery (total hip (THA) or knee (TKA) arthroplasty) and by causative pathogen (methicillin-resistant Staphylococcus aureus (MRSA)) were performed. ResultsOf the 3379 studies identified for screening, six studies involving 5745 patients were included. The use of ALBC significantly reduced the incidence of deep SSI in overall patients (risk ratio [RR] 0.60, 95% confidential interval [CI] 0.39–0.92), but the evidence level was very low. There was no significant preventive effect for ALBC compared with non-ALBC in both THA and TKA (THA, RR 0.52, 95% CI 0.23–1.16; TKA, RR 0.64, 95% CI 0.38–1.06), and for preventing MRSA-SSI (RR 0.27, 95% CI 0.03–2.41). ConclusionsAlthough the overall preventive effect of ALBC was significant, the evidence level was very low. Thus, the routine use of ALBC as a mean to prevent SSI in arthroplasty may not be suggested.

Impact of Antibiotic-Loaded PMMA Spacers on the Osteogenic Potential of hMSCs.

Antibiotic-loaded PMMA bone cement is frequently used in modern trauma and orthopedic surgery. Although many of the antibiotics routinely applied are described to have cytotoxic effects in the literature, clinical experience shows no adverse effects for bone healing. To determine the effects of antibiotic-loaded PMMA spacers on osteogenesis in vitro, we cultivated human bone marrow mesenchymal stem cells (BM-hMSCs) in the presence of PMMA spacers containing Gentamicin, Vancomycin, Gentamicin + Clindamycin as well as Gentamicin + Vancomycin in addition to a blank control (agarose) and PMMA containing no antibiotics. The cell number was assessed with DAPI staining, and the osteogenic potential was evaluated by directly measuring the amount of hydroxyapatite synthesized using radioactive 99mTc-HDP labelling as well as measuring the concentration of calcium and phosphate in the cell culture medium supernatant. The results showed that Gentamicin and Vancomycin as well as their combination show a certain amount of cytotoxicity but no negative effect on osteogenic potential. The combination of Gentamicin and Clindamycin, on the other hand, led to a drastic reduction in both the cell count and the osteogenic potential.

Injectable isoniazid-loaded bone cement based on hydrazone bonds achieving long-term release and decent mechanical properties.

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.

3D-printed antibiotic-loaded bone cement spacers as adjunctive therapy for hip periprosthetic infection after arthroplasty: A clinical assessment

ObjectiveTo explore the effect of 3D-printing technology in assisting the treatment of periprosthetic infection after total hip arthroplasty (THA) by using personalized antibiotic-loaded bone cement (ALBC) spacers. MethodsThe data of 40 patients with postoperative infection after THA were retrospectively analyzed. The patients were divided into 3D printing group (age 47-78 years) and conventional group (age 57-78 years), with 20 cases in each group. In the stage I surgery, the 3D printing group used 3D printed silicone molds to create ALBC spacers, while the conventional group used traditional manual methods. After the infection was controlled, both groups underwent conventional hip revision surgery in the stage II surgery. All patients were evaluated by Harris hip score (HHS) (primary outcome) for hip function. ResultsAll 40 patients had follow-up data, with 3 months after the first stage and 12 months after the second stage. HHS: The intergroup difference was 11.25 points (97.5% confidence interval (CI), 7.92 to 14.58; P <0.01) at 3 months after the first stage, and 9.15 points (97.5% CI, 4.82 to 13.48; P <0.01) at 12 months after the second stage, and the overall difference between the two groups was 9.55 points (97.5% CI, 5.83 to 13.27; P <0.01), which was statistically significant (P<0.05). ConclusionDuring the follow-up period, the hip functional of the 3D printing group were superior to those of the conventional group in the treatment of infections after THA.

Register data on cemented arthroplasty : Aproof for cementless fixation?

Hip and knee implants can be either fixated without cement, press-fit, or with bone cement. Real-world data from arthroplasty registers, as well as studies, provide abroad database for the discussion of cemented versus uncemented arthroplasty procedures. What is the recommendation for cemented or cementless anchorage of hip and knee implants based on the current evidence from international arthroplasty registries and meta-analyses? Arecommendation is generated by means of adirect comparison of data from the arthroplasty registries of eight different countries (USA, Germany, Australia, UK, Sweden, Norway, New Zealand, and The Netherlands), the comparison of 22review studies and meta-analyses based on registry data, as well as the evaluation of the recommendation of healthcare systems of different nations. For this purpose, reviews and meta-analyses whose results were statistically significant were selected, as were the annual reports of the arthroplasty registries that were current at the time of writing. For knee endoprostheses, along survival time, as well as alower risk of revision can be achieved with the help of cemented anchorage with antibiotic-laden bone cement. In patients aged 70years and older, cemented anchorage of the hip stem implant significantly reduces the risk of intraoperative or postoperative periprosthetic fracture (times four), this applies both to elective total hip arthroplasties (TEPs) and to hemiarthroplasty after femoral neck fractures. Antibiotic-loaded bone cement significantly (p = 0.041) reduces the risk of periprosthetic infection, especially in patients with femoral neck fractures. Total knee replacement with antibiotic-loaded bone cement is well established in Germany and evidence based. Registry data and meta-analyses recommend cemented fixation of the hip stem in older patients-in Germany the evidence-based recommendations must still be transferred to daily practice.

Daptomycin-Impregnated PMMA Cement against Vancomycin-Resistant Germs: Dosage, Handling, Elution, Mechanical Stability, and Effectiveness.

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). Mechanical properties and handling characteristics (ISO 5833, DIN 53435), HPLC elution, antimicrobial effectiveness with proliferation assay (DIN 17025), and inhibition zone testing were investigated. 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. 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.

Acute postoperative infections after dual head arthroplasty in geriatric patients

Acute periprosthetic joint infections (PJI) after dual head arthroplasty represent amajor challenge with a1-year mortality rate up to 50% in the mostly multimorbid geriatric patient collective. Due to the limited possibilities of preoperative patient optimization, infection rates of up to 9% have been reported, which is significantly higher than in elective arthroplasty. Atherapeutic gold standard has not yet been established due to the heterogeneous study situation and the lack of prospective randomized studies. The most promising therapeutic option currently appears to be asingle-stage stem replacement in combination with implantation of acup component (conversion to total hip arthroplasty, infection eradication in up to 100%). An approach of débridement, antibiotics, implant retention (DAIR) alone shows significantly poorer success rates (16-82%). Surgical treatment should always be followed by antibiotic treatment with atotal duration of 12weeks. In addition to the established perioperative antibiotic prophylaxis, the use of antibiotic-loaded bone cement seems to be superior to cementless stem fixation in preventing PJI in dual head arthroplasty.

Comparison of the Therapeutic Efficacy of Antibiotic-Loaded Polymeric Tissue Scaffold and Bone Cement in the Regeneration of Infected Bone Tissue.

Background Local antibiotic applications have been used in chronic osteomyelitis and have been defined as an adjunctive treatment method. Biodegradable materials are also used for the same purpose by adding antibiotics. The fact that it does not require additional surgery to be removed is an important advantage. In this study, we intended to develop a new biodegradable drug-loaded polymeric scaffold with good antibiotic release and compare the microbiological results with antibiotic-impregnated bone cement. Methodology A tissue scaffold containing poly(2-hydroxyethyl methacrylate) (PHEMA) was prepared in our laboratory and loaded with ertapenem and daptomycin antibiotics. The surface morphology and pore geometries of drug-loaded and unloaded scaffolds were analyzed by a scanning electron microscope under vacuum. The dose-dependent antiproliferative effects of PHEMA scaffold, drug-loaded scaffold, cement, and drug-loaded cement on osteoblast cells were investigated. To evaluate drug release kinetics, the absorbance values of the scaffold loaded with ertapenem and daptomycin were measured with the spectrometer. For microbiological tests, ertapenem and daptomycin-impregnated cement and scaffold, as well as the control scaffold and cement samples, were investigated for their antibacterial activities on Staphylococcus aureus and Klebsiella pneumoniae strains using the disc diffusion method. These microorganisms are one of the most common microorganisms in osteomyelitis. Results The efficacy of antibiotic-impregnated scaffold and cement on both gram-negative and gram-positive microorganisms was investigated. The daptomycin zone diameter in S. aureus ATCC 29233 strain was 17 mm, whereas it was 24 mm for scaffold and 22 mm for cement. Scaffold was found to be more effective than cement against S. aureus strain. The K. pneumoniae ATCC BAA-2814 strain was found to be resistant to ertapenem, but the zone diameter was 21 mm for scaffold and 20 mm for cement. Ertapenem-loaded scaffold was found to be more effective than cement. It was found that the antimicrobial activity of the scaffold was higher than cement. When we evaluated the release profiles,for the daptomycin-loaded cement group, 98% of daptomycin was cumulatively released within 30 minutes, and for the daptomycin-loaded scaffold group, 100% of daptomycin was cumulatively released in six days. To compare ertapenem-loaded cement and scaffold, 98% of ertapenem was cumulatively released within 10 minutes in the cement group. For the scaffold group, 100% of ertapenem was cumulatively released in 17 days. We found that the scaffold released the antibiotic more slowly and for a longer duration. Therefore, it was thought that the scaffold would be more effective on biofilm and the treatment of osteomyelitis would be more successful. Conclusions The produced scaffold was compared with cement, and it was concluded that the scaffold had better release and antimicrobial efficacy. Scaffold is more advantageous than cement because it is bioeliminable. Thus, there is no need for a second surgical intervention with the likely prevention of mortality and morbidity. Becauseof all these features, the scaffold seems promising in the local treatment of osteomyelitis.

A review on non-leaching antibacterial bone cement for orthopedic surgery: From past to current insights

Antibiotic-loaded bone cements are widely used in orthopedic surgery. However, they present issues such as a short antibiotic release time and antibiotic resistance. These challenges necessitate the development of novel antibacterial bone cements. Non-leaching bone cement containing antibacterial motifs represents a promising advancement in this direction. Antibacterial motifs are incorporated into the cement either covalently or non-covalently, and while they will not be released, they will still exhibit surface antibacterial activity. This review comprehensively examines the structure and antimicrobial activity of prevalent non-leaching antimicrobial bone cements. Additionally, it delves into the characteristics of current methods employed for detecting surface antimicrobial activity. Finally, the future research direction of non-leaching antibacterial bone cement is discussed, with a specific focus on innovative antibacterial motifs, the mechanisms underlying non-leaching antibacterial properties, and the potential synergies achievable by combining non-leaching antibacterial bone cement with traditional antibiotics.

Composite Bone Cements with Enhanced Drug Elution.

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).

Effectiveness of antibiotic-loaded bone cement in total joint arthroplasty at a tertiary medical center: A retrospective cohort study

BackgroundData regarding the effectiveness of antibiotic-loaded bone cement (ALBC) in preventing prosthetic joint infections (PJI) after total joint arthroplasty (TJA) is inconsistent. The objective of this study was to evaluate if the routine use of ALBC influenced the risk of revision surgery due to PJI. MethodsThis is a retrospective cohort study performed between January 2018 and September 2020. Adult patients aged ≥ 18 years who underwent TJA (knee or hip) and received either ALBC or plain cement (PC) were included. The outcome of this study was the rate of revision due to PJI. Multivariate analysis using logistic regression was used to identify factors that may be associated with increased risk of PJI, using STATA 15.1 (StataCorp LP, College Station, Texas, USA). ResultsA total of 844 patients were screened and 319 patients were included. There were 247 patients in ALBC group and 72 patients in the PC group. Only vancomycin powder was used in all ALBC cases, with a 2 g dose in 50% of the cases (dose ranged between 1 g and 8 g). The status of the prosthetic joint was assessed and recorded up to 2 years of the TJA. Overall, the difference in the rates of PJI between the two groups after primary arthroplasty was not statistically significant (5.6% vs 1.4%; p = 0.173; OR, 4.2; 95% CI, 0.5–33). ConclusionALBC was not associated with a reduction in PJI rates after primary TJA. More research is needed to further evaluate the effectiveness of ALBC in preventing PJI.

Comparison of antibacterial activity and biocompatibility of non-leaching nitrofuran bone cement loaded with vancomycin, gentamicin, and tigecycline

BackgroundNon-leaching antibacterial bone cement can generate long-term antibacterial activity, it cannot treat serious infections that have occurred like antibiotic-loaded bone cement. Currently, the antibacterial activity and biocompatibility of non-leaching cement when loaded with antibiotics have yet to be determined.MethodsNon-leaching antibacterial nitrofuran bone cement (NFBC) specimens were prepared with low-dose and high-dose antibiotics. The antibacterial activity and biocompatibility of NFBC loaded with vancomycin, gentamicin, and tigecycline were compared. The agar diffusion method was employed to observe the inhibition zone of the samples against two bacterial strains from day one to day seven. The CCK-8 assay and acute liver and kidney toxicity test were conducted to assess the effects of the samples on mouse embryo osteoblast precursor cells and C57 mice, respectively.ResultsGentamicin-loaded cement exhibited the most potent antibacterial activity, effectively inhibiting both bacterial strains at a low dose. Tigecycline-loaded cement demonstrated superior biocompatibility, showing no acute liver and kidney toxicity in mice and minimal cytotoxicity to osteoblasts.ConclusionsNFBC loaded with gentamicin, vancomycin, and tigecycline not only maintains sustained antibacterial activity but also exhibits excellent biocompatibility.

Role of blood markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection

Objective: To investigate the value of inflammation,coagulation and nutrition markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection(PJI). Methods: A retrospective study was conducted on 70 patients who undertook prosthesis removal and antibiotic-loaded bone cement spacer implantation due to PJI from June 2016 to October 2020 in the Department of Orthopedics,Henan Provincial People's Hospital. There were 28 males and 42 females,aged (65.5±11.9) years (range: 37 to 88 years). Patients were divided into two groups as the successful group and the failed group depended on whether reinfection occurred after prosthesis removal and antibiotic-loaded bone cement spacer implantation at the last follow up. Patient demographics,laboratory values (C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),ESR and CRP ratio (ESR/CRP),white blood cell count(WBC),platelet count(PLT),hemoglobin(HB),total lymphocyte count(TLC),albumin、fibrinogen(FIB),CRP and albumin ratio (CAR),prognostic nutritional index(PNI)),and reinfection rates were assessed. Comparison between groups was conducted by the independent sample t test or χ2 test. Receiver operating characteristic (ROC) curve was plotted,and the area under the curve (AUC),optimal diagnostic threshold,sensitivity,and specificity were analyzed to predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation. Results: All patients were followed up for at least two years,and the follow-up time was (38.4±15.2) months (range: 24 to 66 months). Fifteen patients suffered failure after prosthesis removal and antibiotic-loaded bone cement spacer implantation,while the other 55 patients succeeded. The overall failure rate of prosthesis removal and antibiotic-loaded bone cement spacer implantation in PJI treatment was 21.4%. Level of preoperative CRP(35.9±16.2)mg/L,PLT(280.0±104.0)×109/L and CAR 1.3±0.8 in successful group were lower than CRP (71.7±47.3)mg/L,PLT (364.7±119.3)×109/L and CAR 2.5±2.0 in failed group (all P<0.05).Whereas,level of preoperative ESR/CRP (3.3±3.1), Albumin (35.3±5.2)g/L and PNI 43.6±6.2 in successful group were higher than ESR/CRP (1.6±1.4),Albumin(31.3±4.8)g/L and PNI (39.2±15.1) in failed group (all P<0.05). AUC of ROC curve,optimal threshold value,sensitivity and specificity of CRP,ESR/CRP, PLT, Albumin,CAR and PNI for the predicting failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation were 0.776(95%CI:0.660 to 0.867),35.4 mg/L,86.7%,67.3%;0.725(95%CI:0.605 to 0.825),1.0,60.0%,78.2%;0.713(95%CI:0.593 to 0.815),253,93.3%,47.3%;0.721(95%CI:0.601 to 0.822),35.7,93.3%,49.1%;0.772(95%CI:0.656 to 0.863),1.1,86.7%,67.3%;0.706(95%CI:0.585 to 0.809),45.7,100%,41.8% respectively. Conclusion: In patients with PJI,CRP>35.4,ESR/CRP≤1.0 and CAR>1.1 could predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation.

Nanocomposite orthopaedic bone cement combining long-acting dual antimicrobial drugs

Antibiotic loaded bone cements are widely used in total joint replacement (TJR); despite many limitations such as a burst release which leads to antibiotic concentration below inhibitory levels and possibly contributing to the selection of antibiotic resistant strains. In order to address such limitations and to simultaneously address antibiotic resistance and short-term antimicrobial activity, we developed a nanocomposite bone cement capable of providing a controlled release of antimicrobial agents from bone cement to act as prophylaxis or treatment against prosthetic joint infections (PJIs).Gentamicin and chlorhexidine were loaded in combination on silica nanoparticles surface using layer-by-layer coating technique (LbL) combining hydrolysable and non-hydrolysable polymers.The drug release from the nanocomposite continued for >50 days at concentrations higher than the commercial formulation containing the same amount of antimicrobial drugs, where burst release for few days were observed. Moreover, the nanocomposite bone cement showed superior antimicrobial inhibition without adversely affecting the mechanical properties or the ability of osteoblasts to grow. In vivo experiments with an infected bone lesion model along with mass-spectrometric analysis also provided further evidence of efficacy and safety of the implanted nanocomposite material as well as its prolonged drug eluting profile.The developed nanocomposite bone cement has the potential to reduce PJIs and enable treatment of resistant established infections; moreover, the newly developed LbL based nano-delivery system may also have wider applications in reducing the threat posed by antimicrobial resistance.

Fabrication of injectable antibiotic-loaded apatitic bone cements with prolonged drug delivery for treating post-surgery infections.

Antibiotic-loaded bioactive bone substitutes are widely used for treating various orthopedic diseases and prophylactically to avoid post implantation infection. Calcium deficient hydroxyapatite (also known as apatitic bone cement) is a potential bioactive bone substitute in orthopedics due to its chemical composition similar to that of natural bone minerals. In this study, fabrication of mannitol (a solid porogen) incorporated injectable synthetic (Syn) and eggshell derived (ESD) apatitic bone cements loaded with antibiotics (gentamicin/meropenem/ rifampicin/vancomycin) was investigated. The release kinetics of the antibiotics were studied by fitting them with different kinetic models. All the antibiotics-loaded apatitic bone cements set within clinically accepted setting time (20 ± 2 min) and with good injectability (>70%). The antibiotics released from these bone cements were found to be controlled and sustained throughout the study time. Weibull and Gompertz (applies in least initial burst and sustain drug release rate models) were the best models to predict the release behavior. They cements had acceptable compressive strength (6-10 MPa; in the range of trabecular bone) and were biodegradable (21%-27% within 12 weeks of incubation) in vitro in simulated body fluids at physiological conditions. These bone cements showed excellent antibacterial activity from day 1 onwards and no bacterial colony was found from day 3 onwards. The viability of MG63 cells in vitro after 72 h was significantly higher after 24 h (i.e., ~110%). The cells were well attached and spread over the surface of the cements with extended morphology. The ESD antibiotic-loaded apatitic bone cements showed better injectability, degradation and cytocompatibility compared when compared to Syn antibiotic-loaded apatitic bone cements. Thus, we believe that the ESD antibiotic-loaded apatitic bone cements are suitable as potential injectable bone substitutes to avoid post-operative implant associated and other acute or chronic bone infections.

High-dose dual-antibiotic loaded cement for hip hemiarthroplasty in the UK (WHiTE 8): a randomised controlled trial

Hip fracture is the most common injury requiring treatment in hospital. Controversy exists regarding the use of antibiotic loaded bone cement in hip fractures treated with hemiarthroplasty. We aimed to compare the rate of deep surgical site infection in patients receiving high-dose dual-antibiotic loaded cement versus standard care single-antibiotic loaded cement. We included people aged 60 years and older with a hip fracture attending 26 UK hospitals in this randomised superiority trial. Participants undergoing cemented hemiarthroplasty were randomly allocated in a 1:1 ratio to either a standard care single-antibiotic loaded cement or high-dose dual-antibiotic loaded cement. Participants and outcome assessors were masked to the treatment allocation. The primary outcome was deep surgical site infection at 90 days post-randomisation as defined by the US Centers for Disease Control and Prevention in an as-randomised population of consenting participants with available data at 120 days. Secondary outcomes were quality of life, mortality, antibiotic use, mobility, and residential status at day 120. The trial is registered with ISRCTN15606075. Between Aug 17, 2018, and Aug 5, 2021, 4936 participants were randomly assigned to either standard care single-antibiotic loaded cement (2453 participants) or high-dose dual-antibiotic loaded cement (2483 participants). 38 (1·7%) of 2183 participants with follow-up data in the single-antibiotic loaded cement group had a deep surgical site infection by 90 days post-randomisation, as did 27 (1·2%) of 2214 participants in the high-dose dual-antibiotic loaded cement group (adjusted odds ratio 1·43; 95% CI 0·87-2·35; p=0·16). In this trial, the use of high-dose dual-antibiotic loaded cement did not reduce the rate of deep surgical site deep infection among people aged 60 years or older receiving a hemiarthroplasty for intracapsular fracture of the hip. Heraeus Medical. Supported by the UK National Institute for Health and Care Research Oxford Biomedical Research Centre.