Antibiotic-loaded Bone Cement Research Articles

Combination therapy of negative pressure wound therapy and antibiotic-loaded bone cement for accelerating diabetic foot ulcer healing: A prospective randomised controlled trial.

Negative pressure wound therapy (NPWT) and antibiotic-loaded bone cement (ALBC) are commonly used treatments for diabetic foot ulcers (DFUs). However, the combined efficacy of these two modalities remains unclear. This clinical study aimed to assess the effectiveness and underlying mechanisms of NPWT&ALBC in the management of DFUs. A total of 28 patients were recruited, 16 of whom served as controls and received only NPWT, whilst 12 received NPWT&ALBC. Both groups underwent wound repair surgery following the treatments. Blood samples were obtained to detect infections and inflammation. Wound tissue samples were also collected before and after the intervention to observe changes in inflammation, vascular structure and collagen through tissue staining. Compared with the NPWT group, the NPWT&ALBC group exhibited a superior wound bed, which was characterised by reduced inflammation infiltration and enhanced collagen expression. Immunostaining revealed a decrease in IL-6 levels and an increase in α-SMA, CD68, CD206 and collagen I expression. Western blot analysis demonstrated that NPWT&ALBC led to a decrease in inflammation levels and an increase in vascularization and collagen content. NPWT&ALBC therapy tends to form a wound bed with increased vascularization and M2 macrophage polarisation, which may contribute to DFUs wound healing.

Use of local treatment in managing infections: Focus on antimicrobial locks, beads, and cement.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. The purpose of this review is to describe important considerations with local antimicrobial therapies such as locks, beads, and cement for adjunctive infection management or prevention. Local delivery of antimicrobials with locks, beads, and cement has been used for infection management with retained devices in an effort to improve clinical success. However, their use has been controversial due to conflicting clinical data and logistical issues. Antimicrobial lock therapy (ALT) has been used for both adjunctive treatment and prevention of catheter-related bloodstream infections for certain pathogens and based on patient-specific scenarios. ALT has been a controversial method for sterilizing the catheter lumen by delivering high concentrations of antibiotics with or without heparin into the catheter for prolonged durations. Studies differ regarding the selection and concentrations of antibiotics, dwell duration, presence of heparin in the ALT, clinical outcomes/definitions, and use for prevention or treatment of catheter-related bloodstream infections. Antibiotic beads and cement have been used for various surgical procedures but are predominately considered in orthopedic surgeries. Despite the widespread use of the antibiotic-loaded bone cement in orthopedics, studies differ regarding the selection and concentrations of antibiotics, clinical outcomes/definitions, and use for prevention or treatment of infections. Although antimicrobial locks, beads, and cement are commonly used for adjunctive treatment or prevention of infections, more data are needed to support their use to provide clinical efficacy and safety with consistent antimicrobial selection and logistics.

Does the Addition of Low-Dose Antibiotics Compromise the Mechanical Properties of Polymethylmethacrylate (PMMA)?

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

Global research trends of antibiotic-loaded bone cement: A bibliometric and visualized study

ObjectiveAntibiotic-loaded bone cement (ALBC) plays an indispensable role in the treatment of infectious diseases of bone and joint. Here, we intended to analyze the research status, hot spots and frontiers in the field of ALBC, and to provide reference for future research ideas. MethodsThe related English literature in the field of ALBC in the Web of Science Core Collection database was retrieved from January 1, 2009 to July 11, 2023. VOSviewer was used to extract the information of research constituents or bibliometric items such as authors, institutions, countries, and journals. CiteSpace was used to perform cluster analysis and frontier analysis of key words in ALBC research field. ResultsA total of 1091 literatures related to ALBC research were retrieved, and the annual number of publications showed a steady upward trend in the past 15 years. The high-yield countries and regions are mainly represented by the United States, China (including Taiwan, China) and several European countries, such as Germany, England, Spain, Italy, the Netherlands, etc. The top three institutions with the highest number of publications were Shanghai Jiao Tong University, Chang Gung University and Chang Gung Memorial Hospital in China. Four of the top 10 influential scholars come from Germany, namely Konstantinos Anagnostakos, Volker Alt, Andrej Trampuz, and Bernd Fink. The top 10 high-yield journals had an average of 25 articles per journal and an average of 618.9 citations. The top 3 high-yield journals were Journal of Arthroplasty (57 articles, 1213 citations), Clinical Orthopaedics and Related Research (35 articles, 1119 times cited), and Journal of Orthopaedic Research (29 papers, 488 times cited). The keywords with high frequency were infection (266 times), vancomycin (239 times), bone-cement (219 times), gentamicin (216 times), antibiotics (168 times), osteomyelitis (163 times), etc. The clustering knowledge map of high-frequency keywords could be divided into 4 categories: (1) elution, release, mechanical and antibacterial properties of ALBC; (2) Application of ALBC in revision of prosthetic joint infections (PJIs); (3) Antibiotic types and application forms of ALBC; (4) Application of ALBC in the treatment of osteomyelitis. The keywords with the strongest citation bursts analysis revealed a core ("replacement/arthroplasty") and two stages of development in the field of ALBC research. The first stage (2009–2018) focused more on ALBC drug delivery, release, and infection prevention, while the second stage (2018–2023) mainly focused on ALBC drug elution, mechanical properties, and PJIs revision. Starting from 2018, the keyword with the strongest citation bursts had shifted from "acrylic bone cement" to "periprosthetic joint infection". ConclusionALBC research is steadily on the rise. Arthroplasty related applications continue to be the core of ALBC research. The research hotspot and trend are mainly the application in the prevention and treatment of bone and joint infectious diseases and the elution, release, mechanical and antibacterial properties of ALBC.

Biofilm formation of Staphylococcus aureus on various implants used for surgical treatment of destructive spondylodiscitis

The incidence of spondylodiscitis has witnessed a significant increase in recent decades. Surgical intervention becomes necessary in case of bone destruction to remove infected tissue and restore spinal stability, often involving the implantation of a cage. Despite appropriate treatment, relapses occur in up to 20 percent of cases, resulting in substantial economic and social burdens. The formation of biofilm has been identified as a major contributor to relapse development. Currently, there is no consensus among German-speaking spinal surgeons or in the existing literature regarding the preferred choice of material to minimize relapse rates. Thus, the objective of this study is to investigate whether certain materials used in spinal implants exhibit varying degrees of susceptibility to bacterial attachment, thereby providing valuable insights for improving treatment outcomes.Eight cages of each PEEK, titanium-coated PEEK (Ti-PEEK), titanium (Ti), polyetherketoneketone (PEKK), tantalum (Ta) and antibiotic-loaded bone cement were incubated with 20% human plasma for 24 h. Subsequently, four implants were incubated with S. aureus for 24 h or 48 h each. The biofilm was then removed by sonication and the attained solution plated for Colony Forming Units (CFU) counting. Scanning electron microscopy was used to confirm bacterial attachment. The CFUs have been compared directly and in relation to the cages surface area. The surface area of the implants was PEEK 557 mm2, Ti-PEEK 472 mm2, Ti 985 mm2, PEKK 594 mm2, Ta 706 mm2, bone cement 123 mm2. The mean CFU count per implant and per mm2 surface area after 24 h and after 48 h was calculated. Bone cement was found to have significantly more CFUs per mm2 surface area than the other materials tested. When comparing the CFU count per implant, bone cement was statistically significantly more prone to biofilm formation than PEEK after 48 h. There was no statistical significance between the other materials when comparing both CFU count per mm2 surface area and CFU count per implant. The electron microscopic analysis showed the attachment of the bacteria, as well as production of extracellular polymeric substances (EPS) as a sign for beginning biofilm formation. Antibiotic-loaded bone cement has shown statistically significantly more bacterial attachment than the other examined materials. No difference was found between the other materials regarding bacterial attachment after 24 h and 48 h. Proposed hypotheses for further studies include testing whether differences become apparent after longer incubation or with different pathogens involved in the pathogenesis of pyogenic spondylodiscitis.

MID-TERM RESULTS OF THE NEW ENDO-SPACER TECHNIQUE IN TWO-STAGE SEPTIC EXCHANGE SURGERY FOR PERIPROSTHETIC JOINT INFECTION OF THE HIP

Mechanical failure due to dislocation, fracture and acetabular wear as well as persistence of infection are the main complications associated with the use of hip spacers in the treatment of periprosthetic joint infections (PJI).We have developed a novel, custom-made spacer as part of two-stage septic hip replacement and present the two- to five-year results after reimplantation.We prospectively examined a total of 73 patients over our study period in whom our new spacer technique was used. The technique includes a dual mobility inlay and a cemented straight stem in combination with antibiotic-loaded PMMA bone cement which allows full weight bearing meanwhile the interim period. The follow-up ranged between 24 and 60 months after reimplantation as second stage of a two-stage approach. The patients were contacted as part of the follow-up using a questionnaire concerning reoperation, reinfection as well as hip function by using the Harris Hip Score.72 patients (98,6%) could be reimplanted, one patient is still using the spacer prothesis for 45 months because of excellent functional results with a Harris Hip Score of 95, nevertheless reimplantation is planned. The reinfection rate was less than 7% after reimplantation. The dislocation rate was 5%, and in total there was an overall complication rate of less than 10%. The Harris Hip Score was significantly improved.The ENDO spacer surgical technique is a promising option in the treatment of periprosthetic joint infections (PJI) for two-stage septic exchange with a low dislocation rate and good infection control after reimplantation. In addition, it enables early mobilization with the possibility of full weight-bearing in the interval between spacer implantation and reimplantation.

Cemented Calcar-Guided Short-Stem Prostheses in Geriatric Patients: Short-Term Results from a Prospective Observational Study.

Both cementless and cemented stems have exhibited favorable long-term outcomes in total hip arthroplasty. Nonetheless, in elderly patients, cemented hips offer an advantage due to their reduced risk of periprosthetic fractures. This study aimed to assess the initial outcomes of 28 patients who underwent unilateral cemented total hip arthroplasty utilizing a calcar-guided A2 stem (ARTIQO GmbH, Lüdinghausen, Germany). Various types of antibiotic-loaded bone cement were employed. During follow-up, we recorded demographic data and comorbidities and employed standardized clinical assessment tools, including the Harris Hip Score. Radiographic assessments included preoperative, postoperative, and follow-up imaging to evaluate subsidence, osteolysis, and bone resorption. The results indicated that among the 28 patients, 5 withdrew consent and 2 patients passed away from unrelated causes. Additionally, one prosthesis was explanted due to the undersizing of the cement stopper, which resulted in an inadequate cement mantle. As a result, 20 patients underwent a 1-year follow-up, revealing noteworthy enhancements in clinical scores, with no instances of radiolucent lines or osteolysis. No infections were detected. In summary, our short-term experience with this particular cemented short-stem design yielded promising results, exhibiting excellent functional outcomes, no aseptic loosening attributable to the stem, and no infections. Further clinical studies and registry data are essential to corroborate these findings.

Formulation of three tailed bacteriophages by spray-drying and atomic layer deposition for thermal stability and controlled release

Deep infection is the second most common complication of arthroplasty following loosening of the implant. Antibiotic-loaded bone cements (ALBCs) and high concentrations of systemic broad-spectrum antibiotics are commonly used to prevent infections following injury and surgery. However, clinical data fails to show that ALBCs are effective against deep infection, and negative side effects can result following prolonged administration of antibiotics. Additionally, the rise of multidrug resistant (MDR) bacteria provides an urgent need for alternatives to broad-spectrum antibiotics. Phage therapy, or the use of bacteriophages (viruses that infect bacteria) to target pathogenic bacteria, might offer a safe alternative to combat MDR bacteria. Application of phage therapy in the setting of deep infections requires formulation strategies that would stabilize bacteriophage against chemical and thermal stress during bone-cement polymerization, that maintain bacteriophage activity for weeks or months at physiological temperatures, and that allow for sustained release of phage to combat slow-growing, persistent bacteria. Here, we demonstrate the formulation of three phages that target diverse bacterial pathogens, which includes spray-drying of the particles for enhanced thermal stability at 37 °C and above. Additionally, we use atomic layer deposition (ALD) to coat spray-dried powders with alumina to allow for delayed release of phage from the dry formulations, and potentially protect phage against chemical damage during bone cement polymerization. Together, these findings present a strategy to formulate phages that possess thermal stability and sustained release properties for use in deep infections.

In Vivo Intra-Articular Antibiotic Concentrations at 24 Hours After TKA Fall Below the Minimum Inhibitory Concentration for Most Bacteria: A Randomized Study of Commercially Available Bone Cement.

The use of antibiotic-loaded bone cement (ALBC) to help reduce the risk of infection after primary total knee arthroplasty (TKA) is controversial. There is a paucity of in vivo data on the elution characteristics of ALBC. We aimed to determine whether the antibiotic concentrations of 2 commercially available ALBCs met the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) for common infecting organisms. Forty-five patients undergoing TKA were randomized to receive 1 of the following: bone cement without antibiotic (the negative control; n = 5), a commercially available formulation containing 1 g of tobramycin (n = 20), or a commercially available formulation containing 0.5 g of gentamicin (n = 20). Intra-articular drains were placed, and fluid was collected at 4 and 24 hours postoperatively. An automated immunoassay measuring antibiotic concentration was performed, and the results were compared against published MIC and MBEC thresholds. The ALBC treatment groups were predominantly of White (65%) or Black (32.5%) race and were 57.5% female and 42.4% male. The mean age (and standard deviation) was 72.6 ± 7.2 years in the gentamicin group and 67.6 ± 7.4 years in the tobramycin group. The mean antibiotic concentration in the tobramycin group was 55.1 ± 37.7 μg/mL at 4 hours and 19.5 ± 13.0 μg/mL at 24 hours, and the mean concentration in the gentamicin group was 38.4 ± 25.4 μg/mL at 4 hours and 17.7 ± 15.4 μg/mL at 24 hours. Time and antibiotic concentration had a negative linear correlation coefficient (r = -0.501). Most of the reference MIC levels were reached at 4 hours. However, at 24 hours, a considerable percentage of patients had concentrations below the MIC for many common pathogens, including Staphylococcus epidermidis (gentamicin: 65% to 100% of patients; tobramycin: 50% to 85%), methicillin-sensitive Staphylococcus aureus (gentamicin: 5% to 90%; tobramycin: 5% to 50%), methicillin-resistant S . aureus (gentamicin: 5% to 65%; tobramycin: 50%), Streptococcus species (gentamicin: 10% to 100%), and Cutibacterium acnes (gentamicin: 10% to 65%; tobramycin: 100%). The aforementioned ranges reflect variation in the MIC among different strains of each organism. Gentamicin concentrations reached MBEC threshold values at 4 hours only for the least virulent strains of S . aureus and Escherichia coli. Tobramycin concentrations did not reach the MBEC threshold for any of the bacteria at either time point. The elution of antibiotics from commercially available ALBC decreased rapidly following TKA, and only at 4 hours postoperatively did the mean antibiotic concentrations exceed the MIC for most of the pathogens. Use of commercially available ALBC may not provide substantial antimicrobial coverage following TKA. Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Development of a Galleria mellonella Infection Model to Evaluate the Efficacy of Antibiotic-Loaded Polymethyl Methacrylate (PMMA) Bone Cement.

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

Cement loaded with high-dose gentamicin and clindamycin does not reduce the risk of subsequent infection after aseptic total hip or knee revision arthroplasty: a preliminary study

PurposeThe aim of this study was to quantify the prophylactic effect of high-dose gentamicin and clindamycin antibiotic-loaded bone cement (ALBC) during revision total hip (rTHA) or knee (rTKA) arthroplasty for aseptic reasons. The hypothesis was that the raw surgical site infection (SSI) rate is lower when this particular cement is used in comparison with cement loaded with standard-dose gentamicin during rTHA or rTKA for aseptic reasons.MethodsThis retrospective study included 290 consecutive patients undergoing aseptic rTHA or rTKA. Two consecutive cohorts were defined: the first (control group) involved 145 patients where ALBC with gentamicin only was used; the second (study group) involved 145 patients where ALBC with high-dose gentamicin and clindamycin was used. The primary endpoint was the raw SSI rate after 24 months.ResultsThe raw SSI rate was 8/145 (6%) in the control group and 13/145 (9%) in the study group (odds ratio 0.62, p = 0.26). There was a significant impact of the presence of any risk factor on the SSI rate (15/100 versus 6/169, odds ratio = 4.25, p = 0.002), but no significant impact of any individual risk factor. No complication or side effect related to ALBC was observed in either group.ConclusionThese results do not support the routine use of gentamicin and clindamycin ALBC for fixation of revision implants after rTHA and rTKA for aseptic reasons.

Plasmid-Mediated Spread of Carbapenem Resistance in Enterobacterales: A Three-Year Genome-Based Survey.

The worldwide emergence and dissemination of carbapenem-resistant Gram-negative bacteria (CRGNB) is a challenging problem of antimicrobial resistance today. Outbreaks with CRGNB have severe consequences for both the affected healthcare settings as well as the patients with infection. Thus, bloodstream infections caused by metallo-ß-lactamase-producing Enterobacterales can often have clinical implications, resulting in high mortality rates due to delays in administering effective treatment and the limited availability of treatment options. The overall threat of CRGNB is substantial because carbapenems are used to treat infections caused by ESBL-producing Enterobacterales which also exist with high frequency within the same geographical regions. A genome-based surveillance of 589 CRGNB from 61 hospitals across the federal state Hesse in Germany was implemented using next-generation sequencing (NGS) technology to obtain a high-resolution landscape of carbapenem-resistant isolates over a three-year period (2017-2019). The study examined all reportable CRGNB isolates submitted by participating hospitals. This included isolates carrying known carbapenemases (435) together with carbapenem-resistant non-carbapenemase producers (154). Predominant carbapenemase producers included Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii and Acinetobacter baumannii. Over 80% of 375 carbapenem-resistant determinants including KPC-, NDM-, VIM- and OXA-48-like ones detected in 520 Enterobacterales were plasmid-encoded, and half of these were dominated by a few incompatibility (Inc) types, viz., IncN, IncL/M, IncFII and IncF(K). Our results revealed that plasmids play an extraordinary role in the dissemination of carbapenem resistance in the heterogeneous CRGNB population. The plasmids were also associated with several multispecies dissemination events and local outbreaks throughout the study period, indicating the substantial role of horizontal gene transfer in carbapenemase spread. Furthermore, due to vertical and horizontal plasmid transfer, this can have an impact on implant-associated infections and is therefore important for antibiotic-loaded bone cement and drug-containing devices in orthopedic surgery. Future genomic surveillance projects should increase their focus on plasmid characterization.

Comparable bone penetration between antibiotic-loaded and plain bone cement in total knee arthroplasty.

One of the main concerns around the use of antibiotic-loaded bone cement (ALBC) is the potential reduction in the mechanical properties of the cement when antibiotics are admixed. The purpose of this study was to determine whether there is a difference between plain cement and ALBC in terms of radiological intrusion into the bone in total knee arthroplasties (TKAs). Prospective randomized study of 80 consecutive patients who underwent TKA. Depending on the cement used, patients were divided into two groups by a computer-generated randomization programme: the cement without antibiotic (Group 1) or the ALBC (Group 2). Cement intrusion was measured in postoperative radiographs in eight different regions in the tibial component and six regions in the femoral component. The average cement intrusion was similar in both groups (p = nonsignificance [n.s.]). Group 1 (plain cement) had an average cement intrusion in the femur of 1.4 mm (±0.4) and 2.4 mm (±0.4) in the tibia. In Group 2 (ALBC), the average cement intrusion in the femur came to 1.6 (±0.5) and 2.4 mm (±0.5) in the tibia. In 80% of the patients, the cement intrusion in the tibia averaged a minimum of 2 mm, being similar in both groups (p = n.s.). There are no differences in bone intrusion when comparing plain cement to ALBC. Therefore, the use of ALBC in primary TKA may be indicated, achieving optimal bone penetration. Level I.

Antibiotic-loaded bone cement is associated with a reduction of the risk of revision of total knee arthroplasty: Analysis of the Catalan Arthroplasty Register.

The purpose of this study was to analyse the impact on peri-prosthetic joint infection (PJI) rate and prosthetic survival using antibiotic-loaded bone cement (ALBC) versus plain cement during total knee arthroplasty (TKA). A retrospective cohort study was conducted. The main data source was the Catalan Arthroplasty Register (RACat). TKAs with surgery date between 1 January 2011 and 31 December 2020 were analysed and followed up until 31 December 2023. The main variable of interest was the type of cement (ALBC vs. plain cement), and several endpoints (septic revision, aseptic revision, and all-cause revision) were considered. The analysed outcomes were revision rates, survival rates and risk factors' hazard ratios (HR). A total of 22,781 TKAs were analysed, 13,125 (57.6%) of them with plain cement and 9656 (42.4%) with ALBC. The septic revision rate was lower in the ALBC group after 3 months of follow-up (0.52% vs. 0.78%, p value = 0.04). Prosthetic survival with respect to the aseptic revision endpoint was also higher for the ALBC group during the whole follow-up period (~158 months). Regarding risk factors for infection, ALBC showed a protective effect, HR: 0.53 (0.44, 0.63), while sex (being male) and the analysed comorbidities increased the risk. ALBC is associated with a reduction in both the septic revision and the aseptic revision rate after TKA, and thus with higher prosthetic survival. Level III, Therapeutic, retrospective.

Management of infected bone defects of the femoral shaft by Masquelet technique: sequential internal fixation and nail with plate augmentation

BackgroundTo evaluate the effectiveness of a sequential internal fixation strategy and intramedullary nailing with plate augmentation (IMN/PA) for bone reconstruction in the management of infected femoral shaft defects using the Masquelet technique.MethodsWe performed a retrospective descriptive cohort study of 21 patients (mean age, 36.4 years) with infected bone defects of the femoral shaft treated by the Masquelet technique with a minimum follow-up of 18 months after second stage. After aggressive debridement, temporary stabilisation (T1) was achieved by an antibiotic-loaded bone cement spacer and internal fixation with a bone cement–coated locking plate. At second stage (T2), the spacer and the locking plate were removed following re-debridement, and IMN/PA was used as definitive fixation together with bone grafting. We evaluated the following clinical outcomes: infection recurrence, bone union time, complications, and the affected limb’s knee joint function.ResultsThe median and quartiles of bone defect length was 7 (4.75–9.5) cm. Four patients required iterative debridement for infection recurrence after T1. The median of interval between T1 and T2 was 10 (9–19) weeks. At a median follow-up of 22 (20–27.5) months, none of the patients experienced recurrence of infection. Bone union was achieved at 7 (6–8.5) months in all patients, with one patient experiencing delayed union at the distal end of bone defect due to screws loosening. At the last follow-up, the median of flexion ROM of the knee joint was 120 (105–120.0)°.ConclusionsFor infected femoral shaft bone defects treated by the Masquelet technique, sequential internal fixation and IMN/PA for the reconstruction can provide excellent mechanical stability, which is beneficial for early functional exercise and bone union, and does not increase the rate of infection recurrence.

Use of Hinged Implants for Multistage Revision Knee Arthroplasty for Severe Periprosthetic Joint Infection: Remission Rate and Outcomes After a Minimum Follow-Up of 5 Years

BackgroundIn severe periprosthetic joint infection after total knee arthroplasty (TKA), multistage procedures are indicated for ongoing signs of infection after implant removal during the spacer interval of an intended 2-stage exchange. In these cases, several additional debridement and spacer exchange surgeries may be necessary. Herein, we analyzed the complications, remission rates, and functional outcomes after multistage revision arthroplasty using hinged TKAs. MethodsPatients (n = 79) treated with multistage revision arthroplasty after chronic periprosthetic joint infection of the knee were included (2010 to 2018). During the prosthesis-free interval, a static spacer containing antibiotic-loaded bone cement was implanted. The mean number of surgeries, including implant removal and revision arthroplasty, was 3.8 (range, 3 to 8). The mean duration from implant removal to revision arthroplasty was 83 days (range, 49 to 318). Complications, remission, and mortality were analyzed after a minimum follow-up of 5 years. Outcomes were assessed based on the Knee Society Score (KSS) and the Western Ontario McMasters University Osteoarthritis Index. ResultsDuring follow-up, 24 (30.4%) patients underwent revision surgery, with a mean time to surgical revision of 99 weeks (range, 1 to 261). After follow-up, the infection-free remission rate and overall mortality were 87.3 and 11.4%, respectively. The mean KSS was 74.3 (range, 24 to 99), the KSS Function Score was 60.8 (range, 5 to 100), and the Western Ontario McMasters University Osteoarthritis Index 30.2 (range, 5 to 83). ConclusionsIn difficult-to-treat cases, multistage revision arthroplasty showed high remission rates and low mortality after a follow-up of 5 years. The overall revision rate was comparably high, accounting for early and late reinfections most of the time. In cases of implant survival, functional outcomes comparable to those of revision hinge TKA reported in the literature can be achieved. Therefore, multistage procedures with additional debridement steps should be performed in cases of ongoing infections in intended 2-stage procedures.

Risk Factors and Microbiological Profile of Knee Periprosthetic Joint Infections With Sinus Tract

BackgroundA sinus tract is an abnormal channel that communicates between the skin and the joint, and meets one of the major criteria that is diagnostic of periprosthetic joint infection (PJI). The purpose of this study was to compare the risk factors and the microorganism profile of PJI of the knee with an overlying sinus tract to PJI without a sinus tract. MethodsThis was a retrospective case-control study of PJI following total knee arthroplasty with and without the presence of an overlying sinus tract from 1996 to 2020. There were 2,685 unique cases of chronic PJI following total knee arthroplasty, of which 405 cases (15.1%) had a sinus tract and 2,280 cases (84.9%) did not. Univariate and multivariate analyses were performed to evaluate risk factors and the microorganism profiles of the 2 groups. Odds ratios with 95% confidence intervals were reported. ResultsAfter adjusting for potential confounders in the multivariate analysis, the presence of a sinus tract was associated with a history of severe liver disease (P = .039; odds ratio: 1.99; 95% confidence interval: 1.04 to 3.84). Polymicrobial infections comprised 41.7% of PJI in the sinus tract group, compared to 29.1% in patients who did not have a sinus tract (P < .001). Of the monomicrobial PJI, Staphylococcus aureus (P < .001), Enterococcus faecalis (P < .001), Enterobacter cloacae (P = .002), Corynebacterium species (P = .037), Proteus mirabilis (P = .028), coagulase-negative Staphylococci (P = .019), and Candida albicans (P = .029) were more common in patients who had a sinus tract. ConclusionsThe microbiology profile is significantly different in patients who have PJI of the knee with a sinus tract. These findings can guide the surgeon with surgical planning and selecting the appropriate antibiotic-loaded bone cement and empiric antibiotic treatment.

The effect of different preventive strategies during total joint arthroplasty on periprosthetic joint infection: a network meta-analysis

BackgroundPeriprosthetic joint infection after total joint arthroplasty has a large incidence, and it may often require two or more stages of revision, placing an additional burden on clinicians and patients. The purpose of this network meta-analysis is to evaluate the effect of four different preventive strategies during total joint arthroplasty on the prevention of periprosthetic joint infection.MethodsThe study protocol was registered at PROSPERO (CRD: 42,023,448,868), and the literature search databases included Web of Science, PubMed, OVID Cochrane Central Register of Controlled Trials, OVID EMBASE, and OVID MEDLINE (R) ALL that met the requirements. The network meta-analysis included randomized controlled trials, retrospective cohort studies and prospective cohort studies with the outcome of periprosthetic joint infection. The gemtc R package was applied to perform the network meta-analysis to evaluate the relative results of different preventive strategies.ResultsThis network meta-analysis study included a total of 38 articles with 4 preventive strategies and negative controls. No improvement was observed in antibiotic-loaded bone cement compared with negative controls. Chlorhexidine showed the highest probability of delivering the best preventive effect, and povidone iodine had the second highest probability. Although vancomycin ranked after chlorhexidine and povidone iodine, it still showed a significant difference compared with negative controls. In addition, the incidence after applying chlorhexidine was significantly lower than that after applying negative controls and vancomycin. In the heterogeneity test between direct and indirect evidence, there was no apparent heterogeneity between them.ConclusionThe study indicated that chlorhexidine, povidone iodine and vancomycin showed significant efficacy in preventing periprosthetic joint infection after total joint arthroplasty, while antibiotic-loaded bone cement did not. Therefore, more high-quality randomized controlled trials are needed to verify the results above.

Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe3O4 magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement

Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Primary TKA with ALBC vs plain bone cement. The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.