Aims:The aim of this study was to evaluate the overall mortality rate in patients with periprosthetic joint infection (PJI) after total knee arthroplasty (TKA), the overall mortality over time, and mortality after treatment. Methods:Ovid MEDLINE, Embase, CINAHL, Cochrane Library, Scopus, and Web of Science, were searched for studies reporting the rate of mortality in patients with TKA PJI until December 2023. Full-length studies with extractable data dealing with mortality in these patients were included. Studies were excluded if they involved TKAs which were undertaken for oncological or traumatic indications or septic arthritis, or were partial or revision TKAs. Studies in which primarily high-risk patients, such those with an organ transplant or cancer, were also excluded, in order to allow the mortality rate in patients with PJI after TKA in routine clinical practice to be evaluated. Data were abstracted using a standardized form. Meta-analyses of the proportions with random-effects estimators were used to report the mortality rate after TKA PJI, over time, and after treatment. The study adhered to the 2020 PRISMA guidelines. Results:A total of 83,353 patients with a PJI after TKA from 39 studies were included. At a mean follow-up of 4.4 years (1 month to 17 years), the overall mortality rate after TKA PJI was 13.3% (95% CI 8.8 to 18.5). It was 4.8% (1.2 to 18.0), 7.0% (2.2 to 29.9), and 6.4% (3.0 to 46.0) at three, 12, and 24 months, respectively. The rate significantly differed between the different forms of surgical treatment for PJI (p < 0.001): debridement, antibiotics, and implant retention (DAIR) 12.3% (95% CI 3.9 to 24.0); one-stage exchange arthroplasty 0.47% (95% CI 0 to 1.5); and two-stage exchange arthroplasty 11.5% (95% CI 8.5 to 15.0). There were no significant differences in the mortality rate between patients treated with DAIR and those who underwent a two-stage exchange arthroplasty at three and 12 months. Conclusion:Mortality after TKA PJI remains high, surpassing the five-year rates of mortality in patients with cancer of the breast and prostate. The burden associated with PJI necessitates a multidisciplinary approach and dedicated funding to improve patient care, address this critical issue generally, and reduce mortality.

Periprosthetic joint infection (PJI) is a serious complication of total joint arthroplasty with unclear pathophysiology. This study analyzed protein expression in infected synovial fluid to identify key proteins and pathways involved. This study was conducted at a single academic institution, where patient samples were prospectively collected from August 2023-September 2024. Synovial fluid was obtained during arthroplasty surgery from 33 patients across three groups: (i) primary TKA (n=9), (ii) aseptic revision (n=10), and (iii) septic revision meeting the 2018 ICM criteria for PJI (n=14). Synovial fluid was sent to SomaLogic for proteomic analysis using the 1500 custom SomaScan assay. Fold-change was calculated by first averaging the expression of each group then using the following equation: (Aseptic or Septic expression)/(TKA expression) and transformed using log 2 . Nonparametric false discovery rate (FDR) p-values were calculated using the Wilcoxon rank-sum test and transformed using -log 10 for volcano plot analysis or Kruskall-Wallis test when all groups were compared. Proteins with ≥2-fold change and P-value≤0.05 were considered significant for further analysis. A total of 20 upregulated and 126 downregulated proteins were found in the septic group compared to control TKA, and five upregulated and six downregulated proteins were found in the aseptic group compared to control TKA. Of significantly regulated proteins, three upregulated and five downregulated proteins were shared between aseptic and septic groups suggesting their expression may be a revision-dependent. Further assessment of differential protein expression between groups shows marked upregulation in immune pathways including, immune response and regulatory proteins (fold-change reported septic/aseptic) –VVN2 (12.5, p<0.001), C3 (2.09, p<0.05), HLA-DOB (4.37, p<0.001) and antimicrobial and defense proteins – DEFA4 (5.96, p<0.01), LCN2 (47.03, p<0.001), LTF (2.02, p<0.01), S100A8 (5.33, p<0.001), RNASE3 (4.45, p<0.001), and marked downregulation in immune modulation proteins – LAG3 (-3.91, p<0.001), CD28 (-6.97, p<0.01), CD163 (-7.80, p<0.001), NRP1 (-3.87, p<0.01), IL17-related proteins – IL17RA (-10.64, p<0.001), IL-1RL1 (-2.79, p<0.05), IL-27RA (-4.69. p<0.01) and immune signaling – STAT1 (-5.29, p<0.001) and PRKCA (-4.34, p<0.001) in the septic group only. This first comprehensive proteomic analysis of synovial fluid in periprosthetic joint infection reveals distinct protein expression and pathway activation, uncovering underexplored immune responses and informing future diagnostic and pathophysiology studies.

Data on the risk of postoperative infection and complications related to transient bacteremia in patients who underwent colonoscopy prior to primary total knee arthroplasty (TKA) remain limited. Therefore, we aimed to evaluate the incidence of periprosthetic joint infection (PJI) and other surgical complications in patients who underwent colonoscopy within six months before primary TKA. A retrospective cohort study using an all-payer national database (PearlDiver) was conducted between 2010-2020 to identify adult patients who underwent primary unilateral TKA. Inclusion criteria required one year of postoperative follow-up. Patients who underwent colonoscopy within 6 months preceding TKA were identified (n=25,291). These patients were matched in a 1:1 ratio to patients without a history of colonoscopy using propensity score matching. Matching variables included age, gender, body mass index (BMI), smoking status, Elixhauser comorbidity index (ECI), hypertension, diabetes mellitus, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and cancer diagnosis. Outcomes included 90-day, 1- and 2-year PJI, and postoperative healthcare utilization. There were no significant differences in PJI at 90 days (OR 0.92, p =0.34), 1 year (OR 0.93, p =0.33), or 2 years (OR 0.98, p =0.74) between groups. Patients with prior colonoscopy had higher odds of 90-day ED visits (OR 1.14, p <0.001), reoperations (OR 1.14, p <0.01), and readmissions (OR 1.12, p <0.01), as well as increased 1-year reoperations (OR 1.07, p =0.03). No significant differences were found in rates of 90-day sepsis, surgical site infection (SSI), hematoma, or wound dehiscence ( p >0.05 for all). Stratified analyses by timing of colonoscopy (0–2, 2–4, 4–6 months preoperatively) showed no significant difference in PJI risk compared to patients without colonoscopy ( p >0.05). Colonoscopy within six months before TKA was not associated with an increased risk of PJI. However, its association with higher short-term healthcare utilization warrants further investigation to better understand potential contributing factors.

➢ The rate of periprosthetic joint infection (PJI) is rising globally, with substantial regional variability, and PJI has 5-year mortality rates of 15% to 25%, which exceed those of early-stage breast and prostate cancer and rival those of colorectal and hematologic malignancies.➢ Diagnostic criteria, including synovial fluid analysis, novel culture techniques, and molecular techniques, have improved in accuracy. However, infections caused by fastidious, biofilm-forming microorganisms continue to pose a major diagnostic challenge worldwide.➢ While patient selection remains critical for successful outcomes, the use of DAIR (debridement, antibiotics, and implant retention), 1-stage, 2-stage, and 1.5-stage procedures varies across regions and is often influenced by logistical constraints, resource availability, and clinical expertise. In parallel, discordant definitions of treatment success in the literature hinder comparative research and outcome benchmarking. A tiered framework-encompassing infection eradication, surgical burden, joint function, and patient-reported outcomes-offers a path toward standardized and clinically meaningful reporting.➢ Advances in immunogenetics, artificial intelligence-driven risk modeling, and precision medicine, alongside the emergence of research consortia and global collaborations, are opening new frontiers in treatment strategies and creating opportunities for innovative, individualized approaches to PJI management.

While surgeons typically defer total knee arthroplasty (TKA) during active lower limb infections such as cellulitis, evidence regarding infection risk in patients with recent cellulitis remains sparse. Therefore, this study evaluated the association between cellulitis within three months before TKA and the risk of periprosthetic joint infection (PJI) and postoperative complications. Using an all-payer administrative database (PearlDiver), we identified all patients who underwent unilateral primary TKA between 2010 and 2022. Patients with less than 90 days of follow-up were excluded. Patients who experienced cellulitis within 3 months before TKA (n=1,657, 0.25%) were matched using 1:3 propensity score matching to those without cellulitis (n=4,971) for age, gender, obesity, Elixhauser Comorbidity Index (ECI), smoking, diabetes, hypertension, and heart failure. Outcomes analyzed included the incidence of PJI at 90 days, 1 year, and 2 years postoperatively, as well as the rate of surgical site infections (SSI), sepsis, reoperations, and readmissions within 90 days postoperatively. Multivariate analyses controlled for age, gender, and comorbidity index. Cellulitis within three months before primary TKA was significantly associated with increased odds of 90-day PJI (OR 1.83, 95% CI 1.25–2.67; p<0.01), 1-year PJI (OR 1.94, 95% CI 1.43–2.64; p<0.001), and 2-year PJI (OR 1.93, 95% CI 1.46–2.50; p<0.001). Additionally, recent cellulitis was linked to significantly higher odds of SSI (OR 2.10, 95% CI 1.44–3.06; p<0.001), reoperations (OR 1.51, 95% CI 1.17–1.94; p<0.01), and readmissions (OR 1.50, 95% CI 1.23–1.83; p<0.001). There was no statistically significant association found for 90-day sepsis (OR 1.55, 95% CI 0.82–2.80; p=0.15). One in 400 patients undergoing primary TKA experienced cellulitis in the 3 months before surgery. Lower limb cellulitis in the 3 months before TKA substantially increases the risk of PJI, SSI, reoperations, and readmissions postoperatively. These findings highlight the importance of thorough patient evaluation and optimized multidisciplinary management strategies. Additional research exploring cellulitis resolution timing and its influence on postoperative outcomes is needed.

Background Periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is a rare, but devastating complication with elevated morbidity and mortality. While associated with increased mortality, the reported range is broad and most often reported after 2-stage exchange arthroplasty. This study aimed to report the overall mortality after PJI following primary THA, PJI mortality at one, three, and 12 months, and mortality after common PJI treatments. We hypothesized that mortality after THA PJI would be high, increase over time, and be highest after a 2-stage exchange. Methods A meta-analysis of articles from six databases, queried from inception to December 2023, was performed. Full-length articles reporting mortality following PJI after primary THA were included. Articles with oncologic, infectious, or traumatic THA indications were excluded. Articles investigating high-risk patient populations, including those who had solid organ transplants, active cancer diagnoses, and synchronous PJI, were excluded. There were two independent reviewers who reviewed articles. Mortality over time and after treatment (debridement, antibiotics, and implant retention, 1-stage, and 2-stage exchange arthroplasty) was collected. A meta-analysis of proportions with inverse-variance proportion models was constructed for overall mortality. Results A total of 19,917 patients who had PJI after THA from 20 studies were included. Overall mortality was 11.0% (95% CI [confidence interval]: five to 18.8) at a mean follow-up of 40.3 months (range, one to 240). Pooled mortality at one, three, and 12 months was 1.1, 3.7, and 10.0%, respectively. Mortality following treatment with debridement, antibiotics, and implant retention, 1-stage, and 2-stage exchange was 7.8% (95% CI: 2.3 to 15.9), 1.6% (95% CI: 0 to 14), and 9.2% (95% CI: 5.4 to 13.9), respectively. Considerable heterogeneity was present. Conclusions Mortality after THA PJI is high (11.0%) within three years of arthroplasty and comparable to 5-year rates of cancers, such as breast (11%) and prostate (1%) cancers. A multidisciplinary approach, like those adopted in the treatment of cancer, is warranted to reduce the burden of this devastating complication.

Many patients undergo total meniscectomy before undergoing total knee arthroplasty (TKA). The full impact of prior meniscectomy on TKA remains not well understood. Therefore, we aimed to compare two large TKA cohorts with and without history of meniscectomy. A retrospective cohort study was conducted using the PearlDiver, national database, between 2010-2020 to identify adult patients who underwent primary unilateral TKA for osteoarthritis. Patients with <1 year of follow-up were excluded. TKA patients with a documented history of ipsilateral total meniscectomy (n=41,701) were matched 1:1 to those without such history based on age, gender, body mass index (BMI), smoking, Elixhauser comorbidity index (ECI), hypertension, diabetes mellitus, and congestive heart failure (CHF). Outcomes included 90-day emergency department (ED) visits, reoperations, readmissions, and 1- and 2-year all-cause and infection-related revision rates. All reoperations and revisions occurred on the ipsilateral side. Regression analyses were performed accounting for age, gender, ECI, smoking, and diabetes. In multivariate analyses, patients with a history of meniscectomy had significantly higher odds of adverse postoperative events. Compared to controls, they experienced increased 90-day ED visits (OR 1.23, p<0.001), reoperations (OR 2.10, p<0.001), and readmissions (OR 1.43, p<0.001). History of meniscectomy was also associated with increased 1-year all-cause revision (OR 2.47, p<0.001), 1-year revision for periprosthetic joint infection (PJI) (OR 2.15, p<0.001), and 1-year aseptic revision (OR 2.62, p<0.001). The elevated risk persisted at 2 years for all-cause revision (OR 2.83, p<0.001), revision for PJI (OR 2.33, p<0.001), and aseptic revisions (OR 3.06, p<0.001). A history of total meniscectomy is associated with significantly increased risks of short- and long-term unfavorable outcomes, including ED visits, reoperations, and both septic and aseptic revisions following TKA. These findings suggest the need for heightened preoperative counseling and surveillance in this population.

Patients with immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis (RA) are at higher risk for severe COVID-19 and long-term complications in bone health. Emerging clinical evidence demonstrated that SARS-CoV-2 infection reduces bone turnover and promotes bone loss, but the mechanism underlying worsened bone health remains elusive. This study sought to identify specific immune mediators that exacerbated preexisting IMIDs after SARS-CoV-2 exposure. Plasma samples from 4 groups were analyzed: healthy, IMID only, COVID-19 only, and COVID-19 + IMID. Using high-throughput multiplexed proteomics, we profiled 1,500 protein biomarkers and identified 148 unique biomarkers in COVID-19 patients with IMIDs, including elevated inflammatory cytokines (e.g., IL-17F) and bone resorption markers. Long-term circulating SARS-CoV-2 ORF8, a virulence factor for COVID-19, was detected in the COVID + IMID group. RA was one of the most common IMIDs in our study. ORF8 treatment of RA-derived human osteoblasts (RA-hOBs) increased levels of inflammatory (TNF, IL6, CCL2) and bone resorption (RANKL/osteoprotegerin ratio) markers compared with healthy controls. Supernatants from ORF8-treated RA-hOBs drove the differentiation of macrophages into osteoclast-like cells. These findings suggest that SARS-CoV-2 exposure can exacerbate IMIDs through ORF8-driven inflammation and osteoclastogenesis, highlighting potential therapeutic targets for managing COVID-19-induced bone pathologies.

The success of any clinical trial relies heavily on patient recruitment and retention. The purpose of this study was to review screening and enrollment metrics for orthopaedic clinical trials, comparing different patient populations to determine common challenges to recruitment and differences in rates of enrollment. Screening logs and study trackers were manually reviewed for four clinical trials at a single academic institution and included randomized controlled trials (RCTs) and an observational study. Data extracted from these documents included the number of patients screened, number excluded and reasons for exclusion, number enrolled, number of withdrawn and reason. Of the four trials reviewed, the point-of-care diagnostic test had the highest number of patients excluded and the lowest patient refusal rate. Refusal rates were highest in the venous thromboembolism prophylaxis study and enrollment rates were the lowest in the RCT of drug treatments and the highest rate in the observational study. The success of the trial relies on the ability to recruit patients and factors need to be considered when recruiting participants including sample size requirements and inclusion and exclusion criteria. These data provide some insights into the patient recruitment experience at our institution with different patient populations and study types, highlighting key points to be aware of when planning for an orthopaedic clinical trial.

BACKGROUND:Chronic periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. The underlying pathogenesis often involves the formation of bacterial biofilm that protects the pathogen from both host immune responses and antibiotics. The gold standard treatment requires implant removal, a procedure that carries associated morbidity and mortality risks. Strategies to preserve the implant while treating PJI are desperately needed. Our group has developed an anti-biofilm treatment, PhotothermAA gel, which has shown complete eradication of 2-week-old mature biofilm in vitro. In this study, we tested the anti-biofilm efficacy and safety of PhotothermAA in vivo when combined with debridement, antibiotics and implant retention (DAIR) in a rabbit model of knee PJI. METHODS:New Zealand white rabbits (n = 21) underwent knee joint arthrotomy, titanium tibial implant insertion, and inoculation with Xen36 (bioluminescent Staphylococcus aureus) after capsule closure. At 2 weeks, rabbits underwent sham surgery (n = 6), DAIR (n = 6), or PhotothermAA with DAIR (n = 9) and were sacrificed 2 weeks later to measure implant biofilm burden, soft-tissue infection, and tissue necrosis. RESULTS:The combination of anti-biofilm PhotothermAA with DAIR significantly decreased implant biofilm coverage via scanning electron microscopy compared to DAIR alone (1.8 versus 81.0%; P < .0001). Periprosthetic soft-tissue cultures were significantly decreased in the PhotothermAA with DAIR treatment group (log reduction: Sham 1.6, DAIR 2.0, combination 5.6; P < .0001). Treatment-associated necrosis was absent via gross histology of tissue adjacent to the treatment area (P = .715). CONCLUSIONS:The addition of an anti-biofilm solution like PhotothermAA as a supplement to current treatments that allow implant retention may prove useful in PJI treatment.

Periprosthetic joint infection (PJI) is a multifactorial disease, and the risk of contracting infection is determined by the complex interplays between environmental and host-related factors. While research has shown that certain individuals may have a genetic predisposition for PJI, the existing literature is scarce, and the heterogeneity in the assessed genes limits its clinical applicability. Our review on genetic susceptibility for PJI has the following two objectives: (1) Explore the potential risk of developing PJI based on specific genetic polymorphisms or allelic variations; and (2) Characterize the regulatory cascades involved in the risk of developing PJI. This review focused on clinical studies investigating the association between genetic mutations or variations with the development of PJI. The genes investigated in these studies included toll-like receptors and humoral pattern recognition molecules, cytokines, chemokines, mannose-binding lectin (MBL), bone metabolism molecules, and human leukocyte antigen. Among these genes, polymorphisms in IL-1, MBL, vitamin D receptors, HLA-C, and HLA-DQ might have a relevant impact on the development of PJI. The literature surrounding this topic is limited, but emerging transcriptomic and genome-wide association studies hold promise for identifying at-risk genes. This advancement could pave the way for incorporating genetic testing into preoperative risk stratification, enhancing personalized patient care.

Periprosthetic joint infection is a complication of total joint arthroplasty with treatment costs over 1.6 billion dollars per year in the US with high failure rates. Therefore, generation of coatings that can prevent infection is paramount. Diamond-like carbon (DLC) is an ideal coating for implants as they are wear-resistant, corrosion-resistant, inert, and have a low friction coefficient. The purpose of this study was to test the efficacy of DLC surface treatment in prevention of biofilm on titanium discs infected with Staphylococcus aureus in vitro. Titanium alloy discs (n = 4 non-coated and n = 4 DLC-coated) were infected with 5 × 105 colony-forming units (CFU) of S. aureus for 2 weeks then analysed via crystal violet and scanning electron microscopy (SEM). Crystal violet analysis yielded differences in the appearance of biofilm on implant surface where DLC-coated had a clumpier appearance but no difference in biofilm quantification. Interestingly, this clumpy appearance did lead to differences in SEM biofilm coverage where significantly less biofilm coverage was found on DLC-coated discs (81.78

Bone-related diseases (osteopathologies) associated with human virus infections have increased around the globe. Recent findings have highlighted the intricate interplay between viral infection, the host immune system and the bone remodelling process. Viral infections can disrupt bone homeostasis, contributing to conditions such as arthritis and soft tissue calcifications. Osteopathologies can occur after arbovirus infections such as chikungunya virus, dengue virus and Zika virus, as well as respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 and enteroviruses such as Coxsackievirus B. Here we explore how human viruses dysregulate bone homeostasis, detailing viral factors, molecular mechanisms, host immune response changes and bone remodelling that ultimately result in osteopathologies. We highlight model systems and technologies to advance mechanistic understanding of viral-mediated bone alterations. Finally, we propose potential prophylactic and therapeutic strategies, introduce 'osteovirology' as a research field highlighting the underestimated roles of viruses in bone-related diseases, and discuss research avenues for further investigation.

Periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty. Even with current treatments, failure rates are unacceptably high with a 5-year mortality rate of 26%. Majority of the literature in the field has focused on development of better biomarkers for diagnostics and treatment strategies including innovate antibiotic delivery systems, antibiofilm agents, and bacteriophages. Nevertheless, the role of the immune system, our first line of defense during PJI, is not well understood. Evidence of infection in PJI patients is found within circulation, synovial fluid, and tissue and include numerous cytokines, metabolites, antimicrobial peptides, and soluble receptors that are part of the PJI diagnosis workup. Macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) are initially recruited into the joint by chemokines and cytokines produced by immune cells and bacteria and are activated by pathogen-associated molecular patterns. While these cells are efficient killers of planktonic bacteria by phagocytosis, opsonization, degranulation, and recruitment of adaptive immune cells, biofilm-associated bacteria are troublesome. Biofilm is not only a physical barrier for the immune system but also elicits effector functions. Additionally, bacteria have developed mechanisms to evade the immune system by inactivating effector molecules, promoting killing or anti-inflammatory effector cell phenotypes, and intracellular persistence and dissemination. Understanding these shortcomings and the mechanisms by which bacteria can subvert the immune system may open new approaches to better prepare our own immune system to combat PJI. Furthermore, preoperative immune system assessment and screening for dysregulation may aid in developing preventative interventions to decrease PJI incidence.

Approaches to reverse or limit regulatory T cell (Treg) insufficiency are of great interest for development of immunotherapeutic treatments for autoimmune patients, including type 1 diabetes. Treg insufficiency is heavily implicated in the progression of autoimmune diabetes in the NOD mouse model and is characterized by defects in Treg numbers, development, and/or function. Utilizing a Treg-centric screen, we show that intraislet Tregs have a uniquely dysfunctional phenotype, hallmarked by an almost complete lack of neuropilin-1 (Nrp1), a cell surface receptor required to maintain Treg stability. Intraislet Nrp1– Tregs exhibit hallmark features of fragility, including reduced suppressive capacity, decreased CD73 and Helios, and increased Rorγt and Tbet. Intraislet Nrp1– Tregs also exhibit decreased Foxp3 expression on a per cell basis, suggesting that Nrp1 may also be required for long-term Treg stability. Mechanistically, Treg-restricted augmentation of Nrp1 expression limited the onset of autoimmune diabetes in NOD mice suggesting that Nrp1 critically impacts intraislet Treg function. Transcriptional analysis showed that Nrp1 restoration led to an increase in markers and pathways of TCR signaling, survival, and suppression, and when Nrp1 protein expression is examined by cellular indexing of transcriptomes and epitopes by sequencing, significant differences were observed between Nrp1+ and Nrp1– Tregs in all tissues, particularly in markers of Treg fragility. This translated into substantive differences between Nrp1+ and Nrp1– Tregs that afforded the former with a competitive advantage in the islets. Taken together, these data suggest that maintenance of Nrp1 expression and signaling on Tregs limits diabetes onset and may serve as a strategy to combat Treg insufficiency in autoimmune disease.

» There is conflicting and insufficient evidence that extended oral antibiotic (EOA) therapy prevents infection in high-risk patients undergoing primary total joint arthroplasty (TJA), limiting recommendation for or against the practice.» In the case of aseptic revision TJA, the evidence is also conflicting and limited by underlying confounders, preventing recommendation for use of EOA.» There is fair evidence that use of EOA after debridement antibiotic therapy and implant retention of the prosthesis prolongs infection-free survival, but randomized controlled trials are needed. On the other hand, there is strong evidence that patients undergoing 2-stage revision should receive a period of suppressive oral antibiotics after the second stage.» The optimal duration of EOA in primary TJA, aseptic revision, and debridement antibiotic therapy and implant retention of the prosthesis is unknown. However, there is strong evidence that 3 months of EOA suppression may be appropriate after reimplantation as part of 2-stage exchange arthroplasty.» Complications secondary to EOA are reported to be between 0% and 13.7%, yet are inconsistently reported and poorly defined. The risks associated with antibiotic use, including development of antimicrobial resistance, must be weighed against a possible decrease in infection rate.

» There is conflicting and insufficient evidence that extended oral antibiotic (EOA) therapy prevents infection in high-risk patients undergoing primary total joint arthroplasty (TJA), limiting recommendation for or against the practice.» In the case of aseptic revision TJA, the evidence is also conflicting and limited by underlying confounders, preventing recommendation for use of EOA.» There is fair evidence that use of EOA after debridement antibiotic therapy and implant retention of the prosthesis prolongs infection-free survival, but randomized controlled trials are needed. On the other hand, there is strong evidence that patients undergoing 2-stage revision should receive a period of suppressive oral antibiotics after the second stage.» The optimal duration of EOA in primary TJA, aseptic revision, and debridement antibiotic therapy and implant retention of the prosthesis is unknown. However, there is strong evidence that 3 months of EOA suppression may be appropriate after reimplantation as part of 2-stage exchange arthroplasty.» Complications secondary to EOA are reported to be between 0% and 13.7%, yet are inconsistently reported and poorly defined. The risks associated with antibiotic use, including development of antimicrobial resistance, must be weighed against a possible decrease in infection rate.

Prosthetic joint infection (PJI) is a devastating complication requiring surgical intervention and prolonged antimicrobial treatment. The prevalence of PJI is on the rise, with an average incidence of 60,000 cases per year and a projected annual cost of $1.85 billion in the US. The underlying pathogenesis of PJI involves the formation of bacterial biofilms that protect the pathogen from the host immune response and antibiotics, making it difficult to eradicate such infections. Biofilms on implants are also resistant to mechanical brushing/scrubbing methods of removal. Since the removal of biofilms is currently only achievable by the replacement of the prosthesis, therapies aimed at eradicating biofilms while enabling retention of implants will revolutionize the management of PJIs. To address severe complications associated with biofilm-related infections on implants, we have developed a combination treatment that is based on a hydrogel nanocomposite system, containing d-amino acids (d-AAs) and gold nanorods, which can be delivered and transforms from a solution to a gel state at physiological temperature for sustained release of d-AAs and light-activated thermal treatment of infected sites. Using this two-step approach to utilize a near-infrared light-activated hydrogel nanocomposite system for thermal treatment, following initial disruption with d-AAs, we were able to successfully demonstrate in vitro the total eradication of mature Staphylococcus aureus biofilms grown on three-dimensional printed Ti-6Al-4V alloy implants. Using a combination of cell assays, computer-aided scanning electron microscopy analyses, and confocal microscopy imaging of the biofilm matrix, we could show 100% eradication of the biofilms using our combination treatment. In contrast, we were only able to see 25% eradication of the biofilms using the debridement, antibiotics, and implant retention method. Moreover, our hydrogel nanocomposite-based treatment approach is adaptable in the clinical setting and capable of combating chronic infections brought about by biofilms on medical implants.

Periprosthetic joint infection (PJI) remains a devastating complication after total joint arthroplasty. Bacteria involved in these infections are notorious for adhering to foreign implanted surfaces and generating a biofilm matrix. These biofilms protect the bacteria from antibiotic treatment and the immune system making eradication difficult. Current treatment strategies including debridement, antibiotics, and implant retention, and one- and two-stage revisions still present a relatively high overall failure rate. One of the main shortcomings that has been associated with this high failure rate is the lack of a robust approach to treating bacterial biofilm. Therefore, in this review, we will highlight new strategies that have the potential to combat PJI by targeting biofilm integrity, therefore giving antibiotics and the immune system access to the internal network of the biofilm structure. This combination antibiofilm/antibiotic therapy may be a new strategy for PJI treatment while promoting implant retention.

Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty. The underlying pathogenesis involves the formation of bacterial biofilm that protects the pathogen from the host immune response and antibiotics, making eradication difficult. The aim of this study was to develop a rabbit model of knee PJI that would allow reliable biofilm quantification and permit the study of treatments for PJI. In this work, New Zealand white rabbits ( n=19 ) underwent knee joint arthrotomy, titanium tibial implant insertion, and inoculation with Xen36 (bioluminescent Staphylococcus aureus) or a saline control after capsule closure. Biofilm was quantified via scanning electron microscopy (SEM) of the tibial explant 14 d after inoculation ( n=3 noninfected, n=2 infected). Rabbits underwent debridement, antibiotics, and implant retention (DAIR) ( n=6 ) or sham surgery ( n=2 noninfected, n=6 infected) 14 d after inoculation, and they were sacrificed 14 d post-treatment. Tibial explant and periprosthetic tissues were examined for infection. Laboratory assays supported bacterial infection in infected animals. No differences in weight or C-reactive protein (CRP) were detected after DAIR compared to sham treatment. Biofilm coverage was significantly decreased with DAIR treatment when compared with sham treatment (61.4 % vs. 90.1 %, p<0 .0011) and was absent in noninfected control explants. In summary, we have developed an experimental rabbit hemiarthroplasty knee PJI model with bacterial infection that reliably produces quantifiable biofilm and provides an opportunity to introduce treatments at 14 d. This model may be used to better understand the pathogenesis of this condition and to measure treatment strategies for PJI.