Aims. This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool. Methods. Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures. Results. The JI panel detected microorganisms in 7/48 (14.5%) and 15/67 (22.4%) cases related to UNCs and SPCs, respectively, but not in cases of UPCs. The correlation between JI panel detection and infection classification criteria for early/late acute and chronic PJI was 46.6%, 73%, and 40%, respectively. Overall, the JI panel identified 12.6% additional microorganisms and three new species. The JI panel pathogen identification showed a sensitivity and specificity of 41.4% (95% confidence interval (CI) 33.7 to 49.5) and 91.1% (95% CI 84.7 to 94.9), respectively. In total, 19/195 (9.7%) could have been managed differently and more accurately upon JI panel evaluation. Conclusion. Despite its microbial limitation, JI panel demonstrated clinical usefulness by complementing the traditional methods based on multiple cultures, particularly in PJI with unclear microbiological results. Cite this article: Bone Joint Res 2024;13(7):353–361

Aims. Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections. Methods. Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30). Results. Overall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union. Conclusion. Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications. Cite this article: Bone Jt Open 2023;4(7):516–522

Acute bone and joint infections in children are serious, and misdiagnosis can threaten limb and life. Most young children who present acutely with pain, limping, and/or loss of function have transient synovitis, which will resolve spontaneously within a few days. A minority will have a bone or joint infection. Clinicians are faced with a diagnostic challenge: children with transient synovitis can safely be sent home, but children with bone and joint infection require urgent treatment to avoid complications. Clinicians often respond to this challenge by using a series of rudimentary decision support tools, based on clinical, haematological, and biochemical parameters, to differentiate childhood osteoarticular infection from other diagnoses. However, these tools were developed without methodological expertise in diagnostic accuracy and do not consider the importance of imaging (ultrasound scan and MRI). There is wide variation in clinical practice with regard to the indications, choice, sequence, and timing of imaging. This variation is most likely due to the lack of evidence concerning the role of imaging in acute bone and joint infection in children. We describe the first steps of a large UK multicentre study, funded by the National Institute for Health Research, which seeks to integrate definitively the role of imaging into a decision support tool, developed with the assistance of individuals with expertise in the development of clinical prediction tools. Cite this article: Bone Joint J 2023;105-B(3):227–229

Aims. Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods. We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli. Results. After immunity training, the levels of pro-inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interleukin (IL)-17A) and chemokines (CCL5, CXCL4, CXCL5, CXCL7, CXCL12) increased significantly in platelet releasate, while the levels of anti-inflammatory cytokines (IL-4, IL-13) decreased. Other platelet-secreted factors (e.g. platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, cathepsin D, serotonin, and histamine) were statistically indistinguishable between the two groups. Transfusion of platelets from trained mice into naïve mice reduced infection risk and bacterial burden after local or systemic challenge with either S. aureus or E. coli. Conclusion. Immunity training altered platelet releasate by increasing the levels of inflammatory cytokines/chemokines and decreasing the levels of anti-inflammatory cytokines. Transfusion of platelets from immunity-trained mice conferred protection against bone and joint infection, suggesting that alteration of platelet releasate might be an important mechanism underlying trained immunity and may have clinical implications. Cite this article: Bone Joint Res 2022;11(2):73–81

Aims. This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment. Methods. A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not. Results. A total of 147 patients were included in the no-mNGS group and 88 in the mNGS group. The mNGS group had a higher detection rate of rare pathogens than the no-mNGS group (21.6% vs 10.2%, p = 0.016). However, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and higher infection control rates compared with the no-mNGS group (p = 0.017, p = 0.003, and p = 0.028, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.957). In culture-negative cases, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and a higher infection control rate than the no-mNGS group (p = 0.036, p = 0.033, p = 0.022, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.748). Conclusion. mNGS improves detection of rare pathogens in BJIs. mNGS testing reduces antibiotic-related complications, shortens hospital stay and antibiotic use duration, and improves treatment success rate, benefits which are particularly evident in culture-negative cases. Cite this article: Bone Joint Res 2024;13(8):401–410

Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151

Aim. There have been many attempts to define the criteria by which prosthetic joint infection (PJI) is diagnosed. Our aim is to validate the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI. Method. This is a multicenter retrospective study of patients who have undergone total hip or knee revision surgery in four different European institutions between 2013–2018. Cases with less than four intraoperative microbiology samples; no preoperative/intraoperative synovial fluid differential leukocyte count or intraoperative histology were excluded. Minimum follow-up of at least two years after revision surgery if no subsequent infection and/or the need for implant removal was also required. All cases were classified using the 2021 EBJIS, the 2018 International Consensus Meeting (ICM) and the 2013 Musculoskeletal Infection Society (MSIS) PJI definitions. Results. Definitive PJI classification according to the different definitions of the 507 patients included are presented in table 1. The EBJIS definition classifies 40.4%(205/507) of the cases as confirmed infections compared to 33.9%(p=0.038) and 29.4%(p<0.001) in 2018 ICM and 2013 MSIS classifications respectively. Compared to 2018 ICM classification it also offers significantly less undetermined cases – 5.0% vs. 11.4%(p<0.001). Free from infection Kaplan-Meyer survival curve shows significantly better outcome for EBJIS unlikely compared to confirmed subgroup(p=0.031). EBJIS likely subgroup survival is not significantly different from unlikely(p=0.529) or confirmed(p=0.717) cohorts. Among the MSIS not infected cohort the newly classified EBJIS confirmed/likely cases present higher subsequent infection rate (albeit not statistically significant) when compared to EBJIS infection unlikely cases − 16.0%(13/81) vs. 10.1%(28/277). This subsequent PJI rate is similar to the MSIS infected cohort. A similar trend is not obvious within ICM 2018 not infected subgroup. Conclusions. The EBJIS 2021 definition is shown to be the most sensitive definition while also offering a smaller number of undetermined cases. Newly diagnosed infections seem to have a similar prognosis as “classically” infected cases. For any tables or figures, please contact the authors directly

Aims. There is a paucity of long-term studies analyzing risk factors for failure after single-stage revision for periprosthetic joint infection (PJI) following total hip arthroplasty (THA). We report the mid- to long-term septic and non-septic failure rate of single-stage revision for PJI after THA. Methods. We retrospectively reviewed 88 cases which met the Musculoskeletal Infection Society (MSIS) criteria for PJI. Mean follow-up was seven years (1 to 14). Septic failure was diagnosed with a Delphi-based consensus definition. Any reoperation for mechanical causes in the absence of evidence of infection was considered as non-septic failure. A competing risk regression model was used to evaluate factors associated with septic and non-septic failures. A Kaplan-Meier estimate was used to analyze mortality. Results. The cumulative incidence of septic failure was 8% (95% confidence interval (CI) 3.5 to 15) at one year, 13.8% (95% CI 7.6 to 22) at two years, and 19.7% (95% CI 12 to 28.6) at five and ten years of follow-up. A femoral bone defect worse than Paprosky IIIA (hazard ratio (HR) 13.58 (95% CI 4.86 to 37.93); p < 0.001) and obesity (BMI ≥ 30 kg/m. 2. ; HR 3.88 (95% CI 1.49 to 10.09); p = 0.005) were significantly associated with septic failure. Instability and periprosthetic fracture were the most common reasons for mechanical failure (5.7% and 4.5%, respectively). The cumulative incidence of aseptic failure was 2% (95% CI 0.4 to 7) at two years, 9% (95% CI 4 to 17) at five years, and 12% (95% CI 5 to 22) at ten years. A previous revision to treat PJI was significantly associated with non-septic failure (HR 9.93 (95% CI 1.77 to 55.46); p = 0.009). At the five-year timepoint, 93% of the patients were alive (95% CI 84% to 96%), which fell to 86% (95% CI 75% to 92%) at ten-year follow-up. Conclusion. Massive femoral bone loss was associated with greater chances of developing a further septic failure. All septic failures occurred within the first five years following the one-stage exchange. Surgeons should be aware of instability and periprosthetic fracture being potential causes of further aseptic revision surgery. Cite this article: Bone Joint J 2021;103-B(7):1247–1253

Aims. This study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI). Methods. In this single-centre, retrospective analysis of prospectively collected data, patients with an indicated revision surgery after a total hip or knee arthroplasty were included between 2015 and 2020. A standardized diagnostic workup was performed, identifying the components of the EBJIS, ICM, and IDSA criteria in each patient. Results. Of 206 included patients, 101 (49%) were diagnosed with PJI with the EBJIS definition. IDSA and ICM diagnosed 99 (48%) and 86 (42%) as infected, respectively. A total of 84 cases (41%) had an infection based on all three criteria. In 15 cases (n = 15/206; 7%), PJI was present when applying only the IDSA and EBJIS criteria. No infection was detected by one definition alone. Inconclusive diagnoses occurred more frequently with the ICM criteria (n = 30/206; 15%) compared to EBJIS (likely infections: n = 16/206; 8%) (p = 0.029). A better preoperative performance of the EBJIS definition was seen compared with the ICM and IDSA definitions (p < 0.001). Conclusion. The novel EBJIS definition identified all PJIs diagnosed by any other criteria. Use of the EBJIS definition significantly reduced the number of uncertain diagnoses, allowing easier clinical decision-making. Cite this article: Bone Joint Res 2022;11(9):608–618

Aim. Synovial fluid investigation is the best alternative to diagnose prosthetic joint infection (PJI) before adequate microbiological/histology sampling during revision surgery. Although accurate preoperative diagnosis is certainly recommended, puncturing every patient before revision arthroplasty raises concerns about safety and feasibility issues especially in difficult to access joint (e.g., hip), that often require OR time and fluoroscopy/ultrasound guidance. Currently there is no clear guidelines regarding optimal indications to perform preoperative joint aspiration to diagnose PJI before revision surgery. The main goal of this study is to determine the accuracy of our institutional criteria using the new European Bone and Joint Infection Society (EBJIS) PJI definition. Method. We retrospectively evaluated every single- or first-stage for presumed aseptic or known infected revision total hip/knee arthroplasty procedures between 2013–2020. Preoperative clinical and laboratory features were systematically scrutinized. Cases with insufficient information for accurate final PJI diagnosis (i.e., no perioperative synovial fluid examination or no multiple cultures including sonication of removed implant) were excluded. Preoperative joint aspiration is recommended in our institution if any of the following criteria are met: 1) elevated CRP and/or ESR; 2) early failure (<2 years) or repeat failure; 3) high clinical suspicion/risk factors are present. Performance of such criteria were compared against final postoperative EBJIS definition PJI diagnosis. Results. A total of 364 revision THAs or TKAs were performed during the study period. After excluding 258 cases with insufficient information, a total of 106 patients were ultimately included. 38 (35,8 %) were classified as confirmed infections, 10 (9.4 %) as likely infected and 58 (54.7%) as infection unlikely. Of those, 37 confirmed infection cases, 9 likely infected cases and 32 infection unlikely cases did have indication for preoperative synovial fluid collection before revision surgery. Institutional criteria showed 95.8 % Sensitivity, 44.83 % Specificity, 92.9 % Negative Predictive Value (NPV) and 59 % Positive Predictive Value (PPV). Conclusions. Sensitivity and NPV of the aforementioned institutional criteria are very high even with the use of the more sensitive EBJIS PJI definition. As such they seem to be a valid alternative in selecting patients that should be punctured before revision arthroplasty. They identify the vast majority of infected patients while saving a significant number of patients from unnecessary procedures

Aims. The number of revision arthroplasties being performed in the elderly is expected to rise, including revision for infection. The primary aim of this study was to measure the treatment success rate for octogenarians undergoing revision total hip arthroplasty (THA) for periprosthetic joint infection (PJI) compared to a younger cohort. Secondary outcomes were complications and mortality. Methods. Patients undergoing one- or two-stage revision of a primary THA for PJI between January 2008 and January 2021 were identified. Age, sex, BMI, American Society of Anesthesiologists grade, Charlson Comorbidity Index (CCI), McPherson systemic host grade, and causative organism were collated for all patients. PJI was classified as ‘confirmed’, ‘likely’, or ‘unlikely’ according to the 2021 European Bone and Joint Infection Society criteria. Primary outcomes were complications, reoperation, re-revision, and successful treatment of PJI. A total of 37 patients aged 80 years or older and 120 patients aged under 80 years were identified. The octogenarian group had a significantly lower BMI and significantly higher CCI and McPherson systemic host grades compared to the younger cohort. Results. The majority of patients were planned to undergo two-stage revision, although a significantly higher proportion of the octogenarians did not proceed with the second stage (38.7% (n = 12) vs 14.8% (n = 16); p = 0.003). Although there was some evidence of a lower complication rate in the younger cohort, this did not reach statistical significance (p = 0.065). No significant difference in reoperation (21.6% (n = 8) vs 25.0% (n = 30); p = 0.675) or re-revision rate (8.1% (n = 3) vs 16.7% (n = 20); p = 0.288) was identified between the groups. There was no difference in treatment success between groups (octogenarian 89.2% (n = 33) vs control 82.5% (n = 99); p = 0.444). Conclusion. When compared to a younger cohort, octogenarians did not show a significant difference in complication, re-revision, or treatment success rates. However, given they are less likely to be eligible to proceed with second stage revision, consideration should be given to either single-stage revision or use of an articulated spacer to maximize functional outcomes. Cite this article: Bone Joint J 2024;106-B(8):802–807

Aims. Despite numerous studies focusing on periprosthetic joint infections (PJIs), there are no robust data on the risk factors and timing of metachronous infections. Metachronous PJIs are PJIs that can arise in the same or other artificial joints after a period of time, in patients who have previously had PJI. Methods. Between January 2010 and December 2018, 661 patients with multiple joint prostheses in situ were treated for PJI at our institution. Of these, 73 patients (11%) developed a metachronous PJI (periprosthetic infection in patients who have previously had PJI in another joint, after a lag period) after a mean time interval of 49.5 months (SD 30.24; 7 to 82.9). To identify patient-related risk factors for a metachronous PJI, the following parameters were analyzed: sex; age; BMI; and pre-existing comorbidity. Metachronous infections were divided into three groups: Group 1, metachronous infections in ipsilateral joints; Group 2, metachronous infections of the contralateral lower limb; and Group 3, metachronous infections of the lower and upper limb. Results. We identified a total of 73 metachronous PJIs: 32 PJIs in Group 1, 38 in Group 2, and one in Group 3. The rate of metachronous infection was 11% (73 out 661 cases) at a mean of four years following first infection. Diabetes mellitus incidence was found significantly more frequently in the metachronous infection group than in non-metachronous infection group. The rate of infection in Group 1 (21.1%) was significantly higher (p = 0.049) compared to Groups 2 (6.2%) and 3 (3%). The time interval of metachronous infection development was shorter in adjacent joint infections. Concordance between the bacterium of the first PJI and that of the metachronous PJI in Group 1 (21/34) was significantly higher than Group 2 (13/38; p = 0.001). Conclusion. The findings of this study suggest that metachronous PJI occurs in more than one in ten patients with an index PJI. Female patients, diabetic patients, and patients with a polymicrobial index PJI are at significantly higher risk for developing a metachronous PJI. Furthermore, metachronous PJIs are significantly more likely to occur in an adjacent joint (e.g. ipsilateral hip and knee) as opposed to a more remote site (i.e. contralateral or upper vs lower limb). Additionally, adjacent joint PJIs occur significantly earlier and are more likely to be caused by the same bacteria as the index PJI. Cite this article: Bone Joint J 2023;105-B(3):294–300

Aims. The diagnosis of periprosthetic joint infection (PJI) can be challenging as the symptoms are similar to other conditions, and the markers used for diagnosis have limited sensitivity and specificity. Recent research has suggested using blood cell ratios, such as platelet-to-volume ratio (PVR) and platelet-to-lymphocyte ratio (PLR), to improve diagnostic accuracy. The aim of the study was to further validate the effectiveness of PVR and PLR in diagnosing PJI. Methods. A retrospective review was conducted to assess the accuracy of different marker combinations for diagnosing chronic PJI. A total of 573 patients were included in the study, of which 124 knees and 122 hips had a diagnosis of chronic PJI. Complete blood count and synovial fluid analysis were collected. Recently published blood cell ratio cut-off points were applied to receiver operating characteristic curves for all markers and combinations. The area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated. Results. The results of the analysis showed that the combination of ESR, CRP, synovial white blood cell count (Syn. WBC), and polymorphonuclear neutrophil percentage (PMN%) with PVR had the highest AUC of 0.99 for knees, with sensitivity of 97.73% and specificity of 100%. Similarly, for hips, this combination had an AUC of 0.98, sensitivity of 96.15%, and specificity of 100.00%. Conclusion. This study supports the use of PVR calculated from readily available complete blood counts, combined with established markers, to improve the accuracy in diagnosing chronic PJI in both total hip and knee arthroplasties. Cite this article: Bone Jt Open 2023;4(11):881–888

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area. Cite this article: Bone Joint J 2022;104-B(11):1193–1195

Aims. This study aimed to evaluate the clinical application of the PJI-TNM classification for periprosthetic joint infection (PJI) by determining intraobserver and interobserver reliability. To facilitate its use in clinical practice, an educational app was subsequently developed and evaluated. Methods. A total of ten orthopaedic surgeons classified 20 cases of PJI based on the PJI-TNM classification. Subsequently, the classification was re-evaluated using the PJI-TNM app. Classification accuracy was calculated separately for each subcategory (reinfection, tissue and implant condition, non-human cells, and morbidity of the patient). Fleiss’ kappa and Cohen’s kappa were calculated for interobserver and intraobserver reliability, respectively. Results. Overall, interobserver and intraobserver agreements were substantial across the 20 classified cases. Analyses for the variable ‘reinfection’ revealed an almost perfect interobserver and intraobserver agreement with a classification accuracy of 94.8%. The category 'tissue and implant conditions' showed moderate interobserver and substantial intraobserver reliability, while the classification accuracy was 70.8%. For 'non-human cells,' accuracy was 81.0% and interobserver agreement was moderate with an almost perfect intraobserver reliability. The classification accuracy of the variable 'morbidity of the patient' reached 73.5% with a moderate interobserver agreement, whereas the intraobserver agreement was substantial. The application of the app yielded comparable results across all subgroups. Conclusion. The PJI-TNM classification system captures the heterogeneity of PJI and can be applied with substantial inter- and intraobserver reliability. The PJI-TNM educational app aims to facilitate application in clinical practice. A major limitation was the correct assessment of the implant situation. To eliminate this, a re-evaluation according to intraoperative findings is strongly recommended. Cite this article: Bone Joint Res 2024;13(1):19–27

Aims. Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. Methods. In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated. Results. A total of 52,286 patients were included, of whom 1,804 (3.5%) died. Hypertension, diabetes mellitus, and obesity, the most frequent comorbidities, were not associated with higher in-hospital mortality. Cardiac diseases as atrial fibrillation, cardiac pacemaker, or three-vessel coronary heart disease showed the highest risk for in-hospital mortality. Postoperative anaemia occurred in two-thirds of patients and showed an increased in-hospital mortality (OR 1.72; p < 0.001). Severe complications, such as organ failure, systemic inflammatory response syndrome (SIRS), or septic shock syndrome showed by far the highest association with in-hospital mortality (OR 39.20; 95% CI 33.07 to 46.46; p < 0.001). Conclusion. These findings highlight the menace coming from PJI. It can culminate in multi-organ failure, SIRS, or septic shock syndrome, along with very high rates of in-hospital mortality, thereby highlighting the vulnerability of these patients. Particular attention should be paid to patients with cardiac comorbidities such as atrial fibrillation or three-vessel coronary heart disease. Risk factors should be optimized preoperatively, anticoagulant therapy stopped and restarted on time, and sufficient patient blood management should be emphasized. Cite this article: Bone Jt Open 2024;5(4):367–373

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244

Aims. The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. Methods. A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined. Results. A total of 1,984 HAs were performed during the study period, and 44 sustained a PJI (2.2%). Multiple logistic regression analysis revealed that a higher CCI score (odds ratio (OR) 1.56 (95% confidence interval (CI) 1.117 to 2.187); p = 0.003), peripheral vascular disease (OR 11.34 (95% CI 1.897 to 67.810); p = 0.008), cerebrovascular disease (OR 65.32 (95% CI 22.783 to 187.278); p < 0.001), diabetes (OR 4.82 (95% CI 1.903 to 12.218); p < 0.001), moderate-to-severe renal disease (OR 5.84 (95% CI 1.116 to 30.589); p = 0.037), cancer without metastasis (OR 6.42 (95% CI 1.643 to 25.006); p = 0.007), and metastatic solid tumour (OR 15.64 (95% CI 1.499 to 163.087); p = 0.022) were associated with increasing PJI risk. Upon final follow-up, 17 patients (38.6%) failed initial treatment and required further surgery for HA PJI. One-year mortality was 22.7%. Factors associated with treatment outcome included lower preoperative Hgb level (97.9 g/l (SD 11.4) vs 107.0 g/l (SD 16.1); p = 0.009), elevated CRP level (99.1 mg/l (SD 63.4) vs 56.6 mg/l (SD 47.1); p = 0.030), and type of surgery. There was lower chance of success with DAIR (42.3%) compared to revision HA (66.7%) or revision with conversion to total hip arthroplasty (100%). Early-onset PJI (≤ six weeks) was associated with a higher likelihood of treatment failure (OR 3.5 (95% CI 1.2 to 10.6); p = 0.007) along with patients treated by a non-arthroplasty surgeon (OR 2.5 (95% CI 1.2 to 5.3); p = 0.014). Conclusion. HA PJI initially treated with DAIR is associated with poor chances of success and its value is limited. We strongly recommend consideration of a single-stage revision arthroplasty with cemented components. Cite this article: Bone Jt Open 2022;3(12):924–932

Aims. A higher failure rate has been reported in haematogenous periprosthetic joint infection (PJI) compared to non-haematogenous PJI. The reason for this difference is unknown. We investigated the outcome of haematogenous and non-haematogenous PJI to analyze the risk factors for failure in both groups of patients. Methods. Episodes of knee or hip PJI (defined by the European Bone and Joint Infection Society criteria) treated at our institution between January 2015 and October 2020 were included in a retrospective PJI cohort. Episodes with a follow-up of > one year were stratified by route of infection into haematogenous and non-haematogenous PJI. Probability of failure-free survival was estimated using the Kaplan-Meier method, and compared between groups using log-rank test. Univariate and multivariate analysis was applied to assess risk factors for failure. Results. A total of 305 PJI episodes (174 hips, 131 knees) were allocated to the haematogenous (n = 146) or the non-haematogenous group (n = 159). Among monomicrobial infections, Staphylococcus aureus was the dominant pathogen in haematogenous PJI (76/140, 54%) and coagulase-negative staphylococci in non-haematogenous PJI (57/133, 43%). In both groups, multi-stage exchange (n = 55 (38%) in haematogenous and n = 73 (46%) in non-haematogenous PJI) and prosthesis retention (n = 70 (48%) in haematogenous and n = 48 (30%) in non-haematogenous PJI) were the most common surgical strategies. Median duration of antimicrobial treatment was 13.5 weeks (range, 0.5 to 218 weeks) and similar in both groups. After six years of follow-up, the probability of failure-free survival was significantly lower in haematogenous compared to non-haematogenous PJI (55% vs 74%; p = 0.021). Infection-related mortality was significantly higher in haematogenous than non-haematogenous PJI (7% vs 0% episodes; p = 0.001). Pathogenesis of failure was similar in both groups. Retention of the prosthesis was the only independent risk factor for failure in multivariate analysis in both groups. Conclusion. Treatment failure was significantly higher in haematogenous compared to non-haematogenous PJI. Retention of the prosthesis was the only independent risk factor for failure in both groups. Cite this article: Bone Joint J 2023;105-B(12):1294–1302

Aims. The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition. Methods. This paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance. Results. This process evolved a three-level approach to the diagnostic continuum, resulting in a definition set and guidance, which has been fully endorsed by EBJIS, MSIS, and ESGIAI. Conclusion. The definition presents a novel three-level approach to diagnosis, based on the most robust evidence, which will be useful to clinicians in daily practice. Cite this article: Bone Joint J 2021;103-B(1):18–25

Aim. Serum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP). Method. From January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC). Results. A total of 275 patients with rTHA and rTKA were included, 144 joints (52.4%) were identified as septic. Decreased AGR and elevated CRP were strongly associated with PJI, optimal diagnostic thresholds were calculated with 1.253 and 9.4 mg/L, respectively. Sensitivities were 62.5% (95%-confidence interval: 54.3–70.0) and 73.6% (65.8–80.1), and specificities 84.7% (77.5–89.9) and 87.8% (80.9–92.4), respectively. CRP showed a significantly higher AUC than AGR (0.807 (0.761–0.853) and 0.736 (0.686–0.786); p<0.0001). Subgroup analysis of acute versus chronic infections yielded significantly higher diagnostic accuracies in acute PJI for both parameters (p<0.0001). Similar results were observed when focusing on the causative microorganism; a better diagnostic performance was observed in high-virulence PJI compared to low-virulence PJI (p≤0.005). Furthermore, higher AUCs were calculated in knee PJI compared with hip PJI, with a significant difference for AGR (p=0.043). Conclusions. Due to its limited diagnostic accuracy, serum AGR cannot be recommended as an additional marker for diagnosing PJI. Serum parameters are generally unspecific and can be influenced by comorbidities and other foci of infection. Additionally, parameters may remain within normal levels in low-grade PJI. Evaluating AGR, further possible pitfalls must be considered, for example an increased latency until bottom values are reached and the impact of malnutrition

Aims. To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). Methods. The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. Results. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Conclusion. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI. Cite this article: Bone Joint Res 2023;12(9):559–570

Aim

Accurate diagnosis is key in correctly managing prosthetic joint infection (PJI). Our aim is to compare the preoperative performance of three PJI definitions comparing it to definitive postoperative classification.

Aims. Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections. Methods. We retrospectively collected data from 226 patients (90 hips, 136 knees) with periprosthetic joint infection who underwent two-stage revision between August 2011 and September 2021, with a minimum follow-up of one year. Histology was assessed via the SLIM classification. First, we analyzed whether patients with positive permanent sections at reimplantation had higher reinfection rates than patients with negative histology. Further, we compared permanent and frozen section results, and assessed the influence of anatomical regions (knee versus hip), low- versus high-grade infections, as well as first revision versus multiple prior revisions on the histological result at reimplantation. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), chi-squared tests, and Kaplan-Meier estimates were calculated. Results. Overall, the reinfection rate was 18%. A total of 14 out of 82 patients (17%) with positive permanent sections at reimplantation experienced reinfection, compared to 26 of 144 patients (18%) with negative results (p = 0.996). Neither permanent sections nor fresh frozen sections were significantly associated with reinfection, with a sensitivity of 0.35, specificity of 0.63, PPV of 0.17, NPV of 0.81, and accuracy of 58%. Histology was not significantly associated with reinfection or survival time for any of the analyzed sub-groups. Permanent and frozen section results were in agreement for 91% of cases. Conclusion. Permanent and fresh frozen sections at reimplantation in two-stage revision do not serve as a reliable predictor for reinfection. Cite this article: Bone Joint J 2024;106-B(4):372–379

Aims. The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI). Methods. In this retrospective diagnostic study, patients undergoing revision surgery after total hip or knee arthroplasty (n = 119) between January 2015 and July 2018 were included. Multiple specimens of the periprosthetic membrane and pseudocapsule were obtained for histopathological analysis at revision arthroplasty. Based on the Infectious Diseases Society of America (IDSA) 2013 criteria, the International Consensus Meeting (ICM) 2018 criteria, and the European Bone and Joint Infection Society (EBJIS) 2021 criteria, PJI was defined. Using a mixed effects logistic regression model, the sensitivity and specificity of the histological diagnosis were calculated. The optimal number of periprosthetic tissue specimens for histopathological analysis was determined by applying the Youden index. Results. Based on the EBJIS criteria (excluding histology), 46 (39%) patients were classified as infected. Four to six specimens showed the highest Youden index (four specimens: 0.631; five: 0.634; six: 0.632). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of five tissue specimens were 76.5% (95% confidence interval (CI) 67.6 to 81.4), 86.8% (95% CI 81.3 to 93.5), 66.0% (95% CI 53.2 to 78.7), and 84.3% (95% CI 79.4 to 89.3), respectively. The area under the curve (AUC) was calculated with 0.81 (as a function of the number of tissue specimens). Applying the ICM and IDSA criteria (excluding histology), 40 (34%) and 32 (27%) patients were categorized as septic. Three to five specimens had the highest Youden index (ICM 3: 0.648; 4: 0.651; 5: 0.649) (IDSA 3: 0.627; 4: 0.629; 5: 0.625). Conclusion. Three to six tissue specimens of the periprosthetic membrane and pseudocapsule should be collected at revision arthroplasty and analyzed by a pathologist experienced and skilled in interpreting periprosthetic tissue. Cite this article: Bone Joint J 2023;105-B(2):158–165

Aims. The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results. PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion. This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations. Cite this article: Bone Joint Res 2023;12(10):644–653

Background. Increasing evidence suggests a link between the bearing surface used in total hip arthroplasty (THA) and the occurrence of infection. It is postulated that polyethylene has immunomodulatory effects and may influence bacterial function and survival, thereby impacting the development of periprosthetic joint infection (PJI). This study aimed to investigate the association between polyethylene type and revision surgery for PJI in THA using data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). We hypothesized that the use of XLPE would demonstrate a statistically significant reduction in revision rates due to PJI compared to N-XLPE. Methods. Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) spanning September 1, 1999, to December 31, 2021, were used to compare the infection revision rates between THA using N-XLPE and XLPE. We calculated the Cumulative Percentage Revision rate (CPR) and Hazard Ratio (HR) while controlling for factors like age, sex, body mass index (BMI), American Society of Anesthesiologists’ (ASA) grade, and head size. Results. From the total 361,083 primary THAs, 26,827 used N-XLPE and 334,256 used XLPE. Excluding data from the first 6 months post-surgery, 220 revisions occurred in the N-XLPE group and 1,055 in the XLPE group for PJI. The HR for infection revision was significantly higher in N-XLPE compared to XLPE, at 1.64 (95% CI, 1.41–1.90, p<0.001). Conclusions. This analysis provides evidence of an association between N-XLPE and revision for infection in THA. We suspect that polyethylene wear particles contribute to the susceptibility of THA to PJI, resulting in a significantly higher risk of revision for infection in N-XLPE hips compared to those with XLPE. Level of Evidence. Therapeutic Level III

Aims. Despite numerous studies on periprosthetic joint infections (PJI), there are no robust data on the risk factors and timing of metachronous infections. This study was performed to answer the following questions: 1) Is there any difference of manifestation time of metachronous PJIs between different localizations of multiple artificial joints? 2) Can we identify any specific risk factor for metachronous PJIs for different localizations of multiple artificial joints?. Methods. Between January 2010 and December 2018, 661 patients with more than one prosthetic joint at the time of PJI surgical treatment were recruited. Seventy-one developed metachronous PJI after a mean time interval of 101.4 months (range 37.5 to 161.5 months). The remaining patients were chosen as control group. The diagnosis of the PJI, including the metachronous PJI, was made according to the Muscoloskeletal Infection Society (MSIS) criteria. The metachronous infections were divided in group 1: metachronous infections in the same extremity (e.g. right hip and right knee); group 2: metachronous infections of the other extremity (e.g. right knee and left hip); group 3: metachronous infections of the lower extremity and upper extremity (e.g. right knee and left shoulder). Results. We identified 32 PJI cases in group 1, 38 in group 2 and 1 in group 3. Diabetes mellitus was found higher in the metachronous infections (p<0.05). Rate of same side infection was significantly higher compared to contralateral and upper and lower infection (p<0.05). Time interval of metachrononous infection development was faster in same-side infections. Same bacteria sample rate between primary PJI and metachronous PJI in same side infections (21/32) was significantly higher than in the contralateral PJI group (13/38, p<0.05). Conclusions. The current study underlined that the risk of metachronous infections are relatively high, particularly in the cases of prostheses on the same side

Aims. Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy. Methods. We reviewed our institutional joint arthroplasty database and identified 41 patients diagnosed with fungal PJIs and treated with two-stage exchange arthroplasty after primary total knee arthroplasty (TKA) between January 2001 and December 2020, and compared them with those who had non-fungal PJIs during the same period. After propensity score matching based on age, sex, BMI, American Society of Anesthesiologists grade, and Charlson Comorbidity Index, 40 patients in each group were successfully matched. The surgical and antimicrobial treatment, patient demographic and clinical characteristics, recurrent infections, survival rates, and relevant risk factors that affected joint survivorship were analyzed. We defined treatment success as a well-functioning arthroplasty without any signs of a PJI, and without antimicrobial suppression, at a minimum follow-up of two years from the time of reimplantation. Results. The fungal PJI group demonstrated a significantly worse treatment success rate at the final follow-up than the non-fungal PJI group (65.0% (26/40) vs 85.0% (34/40); p < 0.001). The mean prosthesis-free interval was longer in the fungal PJI group than in the non-fungal PJI group (6.7 weeks (SD 5.8) vs 4.1 weeks (SD 2.5); p = 0.020). The rate of survivorship free from reinfection was worse in the fungal PJI group (83.4% (95% confidence interval (CI) 64.1 to 92.9) at one year and 76.4% (95% CI 52.4 to 89.4) at two years) than in the non-fungal PJI group (97.4% (95% CI 82.7 to 99.6) at one year and 90.3% (95% CI 72.2 to 96.9) at two years), but the differences were not significant (p = 0.270). Cox proportional hazard regression analysis identified the duration of the prosthesis-free interval as a potential risk factor for failure (hazard ratio 1.128 (95% CI 1.003 to 1.268); p = 0.043). Conclusion. Fungal PJIs had a lower treatment success rate than non-fungal PJIs despite two-stage revision arthroplasty and appropriate antifungal treatment. Our findings highlight the need for further developments in treating fungal PJIs. Cite this article: Bone Joint J 2023;105-B(12):1286–1293

Aims. Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. Methods. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test. Results. AGR, CAR, and CRP were associated with PJI (p < 0.001). Sensitivities were 62.5% (95% CI 54.3 to 70.0), 73.6% (95% CI 65.8 to 80.1), and 71.5% (95% CI 63.6 to 78.3), respectively. Specificities were calculated with 84.7% (95% CI 77.5 to 89.9), 86.3% (95% CI 79.2 to 91.2), and 87.8% (95% CI 80.9 to 92.4), respectively. The AUC of CRP (0.797 (95% CI 0.750 to 0.843)) was significantly higher than the AUC of AGR (0.736 (95% CI 0.686 to 0.786), p < 0.001), and similar to AUC of CAR (0.799 (95% CI 0.753 to 0.846), p = 0.832). Decreased sensitivities were observed in PJIs caused by low-virulence organisms (AGR: 60%, CAR: 78%) compared to high-virulence pathogens (AGR: 80%, p = 0.042; CAR: 88%, p = 0.158). Higher sensitivities were seen in acute haematogenous (AGR: 83%, CAR: 96%) compared to chronic PJIs (AGR: 54%, p = 0.001; CAR: 65%, p < 0.001). Conclusion. Serum AGR and CAR showed limited diagnostic accuracy (especially in low-grade and chronic infections) and did not outperform the established marker CRP in our study. Hence, neither parameter can be recommended as an additional tool for diagnosing PJI. Cite this article: Bone Joint Res 2024;13(8):372–382

Aims. This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). Methods. In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. Results. The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. Conclusion. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly. Cite this article: Bone Joint Res 2023;12(2):113–120

Background. The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice and the analysis of synovial fluid (SF) is a useful diagnostic tool. Recently, two synovial biomarkers (leukocyte esterase (LE) strip test, alpha-defensin (AD)) have been introduced into the MSIS (MusculoSkeletal Infection Society) algorithm for the diagnosis of PJI. AD, although promising with high sensitivity and specificity, remains expensive. Calprotectin is another protein released upon activation of articular neutrophils. The determination of calprotectin and joint CRP is feasible in a routine laboratory practice with low cost. Purpose. Our objective was to evaluate different synovial biomarkers (calprotectin, LE, CRP) for the diagnosis of PJI. Methods. In this monocentric study, we collected SF from hip, knee, ankle and shoulder joints of 42 patients who underwent revision or puncture for diagnostic purposes. Exclusion criteria included a joint surgery in the previous 3 months and a diagnosis of a systemic inflammatory disease. PJI was diagnosed in a multidisciplinary consultation meeting (RCP) of the Reference Centers for Osteoarticular Infections of the Great West (CRIOGO). SF was analysed for LE, CRP and calprotectin. The cut-off values used were 50 mg/L for calprotectin, 8.8 mg/L for CRP and 125 WBC/µL for LE. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for these different synovial markers. Results. Of the 42 patients included, 28 were considered as infected and 14 uninfected. The statistical parameters are presented in Table 1. Conclusion. The present study shows that the synovial calprotectin assay has an excellent sensitivity and a 100% NPV for the diagnosis of PJI, suggesting that a result < 50 mg/L could exclude PJI. This promising study suggests that calprotectin should be included with synovial CRP in a new decision algorithm for the diagnosis of PJI. For any tables or figures, please contact the authors directly

Aims. The aim of this study was to evaluate the diagnostic accuracy of the absolute synovial polymorphonuclear neutrophil cell (PMN) count for the diagnosis or exclusion of periprosthetic joint infection (PJI) after total hip (THA) or knee arthroplasty (TKA). Methods. In this retrospective cohort study, 147 consecutive patients with acute or chronic complaints following THA and TKA were included. Diagnosis of PJI was established based on the 2018 International Consensus Meeting criteria. A total of 39 patients diagnosed with PJI (32 chronic and seven acute) and 108 patients with aseptic complications were surgically revised. Results. Using receiver operating characteristic curves and calculating the area under the curve (AUC), an optimal synovial cut-off value of 2,000 PMN/µl was determined (AUC 0.978 (95% confidence interval (CI) 0.946 to 1)). Using this cut-off, sensitivity and specificity of absolute synovial PMN count for PJI were 97.4% (95% CI 91.2 to 100) and 93.5% (95% CI 88.9 to 98.1), respectively. Positive and negative predictive value were 84.4% (95% CI 72.7 to 93.9) and 99.0% (95% CI 96.7 to 100), respectively. Exclusion of 20 patients with acute complications improved specificity to 97.9% (95% CI 94.6 to 100). Different cut-off values for THA (< 3,600 PMN/µl) and TKA (< 2,000 PMN/µl) were identified. Absolute synovial PMN count correlated strongly with synovial alpha-defensin (AD) (r = 0.759; p < 0.001). With a positive AD result, no additional PJI could be identified in any case. Conclusion. Absolute synovial PMN count is a widely available, rapid, cost-effective, and accurate marker in PJI diagnostics, whereas synovial AD appears to be a surrogate parameter of absolute synovial PMN count. Despite limitations in the early postoperative phase, wear, and rheumatic diseases in confirming PJI, an absolute synovial PMN count below 2,000/µl is highly suitable for ruling out PJI, with specific cut-off values for THA and TKA. Cite this article: Bone Joint J 2023;105-B(4):373–381

Aims. Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI. Methods. From 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined. Results. Eradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures). Conclusion. Therapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results. Cite this article: Bone Jt Open 2021;2(8):671–678

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI. Cite this article: Bone Joint J 2022;104-B(5):575–580

Introduction. Vancomycin is a commonly used antibiotic for prophylaxis in total joint replacement surgery. Several studies have reported superior local tissue concentration of vancomycin using intraosseous (IO) infusion compared with standard intravenous (IV) administration in total knee arthroplasty (TKA). We reviewed patients undergoing primary TKA who received IO vancomycin to a group receiving IV vancomycin. Methods. A retrospective review of 1038 patient who underwent primary TKA at our institution was performed from May 1, 2016 to May 1, 2019. This was a consecutive series of patients before and after we adopted this technique. IO vancomycin administration technique has been previously reported from our institution (500mg vancomycin in 200mL solution). Comparisons included preoperative and postoperative creatinine values, adverse reaction to vancomycin, tourniquet time, re-operation rates, periprosthetic joint infection rate at 1 year. Results. There were 482 patients in IO vancomycin group and 572 patients in IV vancomycin group. No differences between groups were present for patient age, sex, or BMI. No differences in creatinine values or tourniquet time were present and there were no adverse reactions to vancomycin in either group. Eight periprosthetic joint infections (1.4%) were reported in the IV group, and 1 (0.2%) periprosthetic joint infection was reported in the IO group at 1 year follow up, and this was statistically significant (p = 0.04, Fishers exact test). The overall reoperation rate was 1.7% (10 patients) in the IV group and 1.1% (5 patients), however, this was not statistically significant (p = 0.4371). The additional reoperations were for retained suture or small areas of poor superficial wound healing and were considered minor. Conclusion. Our study demonstrated that IO vancomycin in primary TKA reduced periprosthetic joint infection and is a safe and effective alternative to IV administration. Furthermore, IO infusion also eliminates the logistical challenges of timely prophylactic antibiotic administration before TKA

Aims. A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. Methods. A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed. Results. Biopsy samples from the GMED from infected patients revealed a larger fibril diameter than control patients, as seen in the TEM (p < 0.001). Uninfected patients were slightly older and had their revisions performed significantly later than the infected patients. Histologically, samples from infected patients revealed significantly more vascularity (p < 0.001), the presence of glycosaminoglycans (p < 0.001), and a higher TDS (p = 0.003) than the control patients. The majority of patients had staphylococcal infections of various species. Conclusion. More histological degeneration in the GMED was found in patients undergoing THA revision surgery due to PJI than in patients undergoing THA revision surgery due to other reasons. Cite this article: Bone Jt Open 2023;4(8):628–635

Aim. Several options to standardize the definition of periprosthetic joint infection (PJI) have been created including the 2013 Musculoskeletal Infection Society (MSIS), 2018 Intentional Consensus Meeting (ICM), and the 2019 proposed European Bone and Joint Infection Society (EBJIS) criteria. Synovial fluid biomarkers have been investigated in an effort to simplify and improve the diagnosis of PJI. The aim of this study was to test the sensitivity, specificity, positive, and negative predicted values (PPV and NPV, respectively) of a calprotectin point of care (POC) test for diagnosing PJI in revision total knee arthroplasty (TKA) patients comparing different sets of criteria (2013 MSIS, 2018 ICM, and 2019 EBJIS criteria) used to define patients as with or without infection. Method. From October 2018 to January 2020 and under IRB approval 123 intraoperative samples of synovial fluid were prospectively collected at two academic hospitals in the same institution from revision TKA patients. All patients underwent standard clinical and laboratory evaluation for PJI at our institution, allowing for categorization using the 3 criteria. Patients were adjudicated by 2 blinded and independent reviewers for the 3 sets of criteria. The 3 criteria agreed 91.8% of the time. Four likely cases by the 2019 proposed EBJIS were considered unlikely and 1 inconclusive case by the 2018 ICM was considered not infected for the purposes of analysis. Calprotectin POC testing followed manufacturer's instructions using a threshold of >50 mg/L to indicate PJI. Sensitivities, specificities, PPV, NPV, and areas under the curve (AUC) were calculated for the 3 sets of criteria. Results. Using 2013 MSIS criteria the calprotectin POC test demonstrated a sensitivity, specificity, PPV, NPV AUC of 98.1%, 95.7%, 94.5%, 98.5%, and 0.969, respectively. Using 2018 ICM the POC test demonstrated a sensitivity, specificity, PPV, NPV and (AUC) of 98.2%, 98.5%, 98.2%, 98.5%, and 0.984, respectively. Using the 2019 proposed EBJIS criteria the POC test demonstrated a sensitivity, specificity, PPV, NPV and area under the curve (AUC) of 93.2%, 100.0%, 100.0%, 94.2%, and 0.966, respectively. Conclusions. The calprotectin lateral flow POC test has an excellent sensitivity and specificity regardless of the set of criteria used to define PJI. These results are promising and suggest that the calprotectin lateral flow test may be used as a rule out test in a cost-conscious health care model or when conventional diagnostic tools may not be available. Further investigations of the calprotectin PCO test must be completed to validate these results

Aims. The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld. Methods. A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. Results. None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). Conclusion. When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J 2022;104-B(1):183–188

Aim

Corynebacterium is a rare etiologic agent of BJI. We aimed to describe this rare clinical condition and to assess treatment failure determinants.

Aim. Patients with late acute periprosthetic joint infections (PJI) and treated with surgical debridement have a high failure rate. Previous studies have shown that rheumatoid arthritis (RA) is an independent risk factor for treatment failure. We conducted a case-control study to identify predictors for failure in late acute PJI treatment in RA patients. We hypothesize that patients with RA have a higher failure rate compared to controls due to the use of immunosuppressive drugs. Method. Data of an international multicenter retrospective observational study was used. Late acute PJI was defined as a sudden onset of symptoms and signs of a PJI, more than 3 months after implantation. Failure of treatment was defined as persistent signs of infection, relapse with the same or reinfection with a different micro-organism, need for prosthesis removal or death. Cases with RA were matched with cases without RA based on the affected joint. A Cox survival analyses, stratified for RA, was used to calculate hazard ratio's (HR) for failure. Subgroup analyses were used to explore other predictors for treatment failure in RA patients. Results. A total of 40 patients with RA and 80 controls without RA were included. Treatment failure occurred in 65% patients with RA compared to 45% for controls (p= .052). 68% of patients with RA used immunosuppressive drugs at time of PJI diagnosis. The use or continuation of immunosuppressive drugs in PJI was not associated with a higher failure rate; neither were the duration of symptoms and causative microorganism. The time between implantation of the prosthetic joint and diagnosis of infection was longer in RA patients: median 110 (IQR 41-171) vs 29 months (IQR 7.5–101.25). Exchange of mobile components was associated with a lower risk of treatment failure (HR 0.489, 95% CI 0.242–0.989, p-value .047). Conclusions. The use of immunosuppressive drugs does not seem to be associated with a higher failure rate in patients with RA. Mobile exchange in RA patients is associated with a lower risk of failure. This might be due to the significantly older age of the prosthesis in RA patients. Future studies are needed to explore these associations and its underlying pathogenesis

Aim. To investigate the impact of waiting for surgical treatment for bone and joint infection (BJI) on patient self-reported quality of life (QoL). Method. Patients presenting to clinic between January 2019 and February 2020 completed the EuroQol EQ-5D-5L questionnaire. Patients were divided into three groups: surgery performed; on the waiting list for surgery; or decision for non-operative management. All patients were followed-up for 2 years. The EQ-index score was calculated and change from presentation to 1-year and 2-year follow-up was compared across the 3 groups. Mortality at final follow-up was measured in all groups. Results. 188 patients were included. Of these, 98 had an operation performed, 50 were on the waiting list for surgery but did not receive an operation and 40 were treated non-operatively. At presentation, all three groups had similar EQ-5D-5L index scores (surgery:0.412 SD0.351; waiting list:0.510 SD0.320; non-operative management: 0.467 SD0.354; p=0.269). There was a significant improvement in QoL in patients who underwent surgery when compared to their pre-operative state (mean increase of EQ-index score +0.241 in the first year (SD0.333, p<0.001) and +0.259 (SD0.294, p<0.001) in the second year. Patients on the waiting list for surgery had a small time-dependent decrease in EQ-index score at 1 year (−0.077, SD0.282, p=0.188) and 2 years (−0.140, SD0.359, p=0.401). Patients treated non-operatively had similar changes in EQ-index scores at 1 year (−0.052, SD0.309, p=0.561) and 2 years (−0.146, SD 0.234, p=0.221). Patients who had surgery had significantly better QoL at 2-years after treatment compared to other groups (mean EQ-index scores: surgery performed 0.671 vs. waiting list 0.431, p<0.001; surgery performed vs. non-operative management 0.348, p<0.001). Mortality in the operated group was 3.1%, which was similar to patients who were on the waiting list for surgery (6.5%, p=0.394) but lower than patients who were non-operatively managed (14.7%, p=0.014). Conclusions. The Covid-19 pandemic created long waiting times for some patients. Selecting patients with BJI who can safely wait for surgery is difficult. QoL for patients with BJI deteriorates over time if surgery is delayed or not performed. When patients decline surgery, they should be counselled that their QoL is likely to be impaired over time. The relationship between waiting time and mortality merits further study

Elevated synovial leukocyte count is a minor criterion derived from the musculoskeletal infection society (MSIS) widely used in clinical practice for diagnosis of prosthetic joint infection. There is evidence to suggest analysis within 1 hour, preferentially within 30 minutes, of aspiration reduces the risk of ex vivo cell lysis occurring during prolonged transport. Multiple site working is more common practice and the availability of a lab on site to perform these tests is not always possible. We aimed to assess whether we could safely perform synovial leukocyte counts within our cold site in the diagnosis of prosthetic joint infection. We reviewed all orthopaedic synovial fluid aspirates within the lower limb arthroplasty unit from April 2021 – April 2022 performed at South Tees NHS Foundation Trust. We assessed time from aspirate to the lab using electronic data resources. This information was compared with the labs ability to perform a synovial leukocyte count to determine the impact of delays on testing. 110 patients (34.5% hips and 63.6% knees) were identified between two sites. Time from aspirate to lab ranged from 0 mins to 26 hrs 34 mins. Mean time to processing was 3hrs 10 mins. 50% of all samples had a synovial leukocyte count performed. 67% of patients had a cell differential performed. There was no difference in the ability to perform a synovial leukocyte count between samples process in < 2hours vs > 6 hours. We conclude that it is safe practice to perform joint aspirates for the work up of periprosthetic joint infections in sites where no laboratory is immediately available as the delay to processing synovial fluid does not alter the ability to perform a synovial leukocyte count. This study will provide evidence to enable the work up of periprosthetic joint infections in cold centres and therefore reduce the delay in diagnosis and proceeding management

Aims. This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI). Methods. A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR). Results. SCVs can be isolated from samples collected from chronic PJIs intraoperatively. Transmission electron microscopy (TEM) and immunofluorescence (IF) showed that there was more S. aureus in bone samples collected from chronic PJIs, but much less in bone samples from acute PJIs, providing a potential mechanism of PJI. Immunofluorescence results showed that SCVs of S. aureus were more likely to invade osteoblasts in vitro. Furthermore, TEM and IF also demonstrated that SCVs of S. aureus were more likely to invade and colonize in vivo. Cluster analysis and principal component analysis (PCA) showed that there were substantial differences in gene expression profiles between chronic and acute PJI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these differentially expressed genes were enriched to chemokine-related signal pathways. PCR also verified these results. Conclusion. Our study has shown that the S. aureus SCVs have a greater ability to invade and colonize in bone, resulting in S. aureus remaining in bone tissues long-term, thus explaining the pathogenesis of chronic PJI. Cite this article: Bone Joint Res 2022;11(12):843–853

Aims. One-stage exchange for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) is gaining popularity. The outcome for a repeat one-stage revision THA after a failed one-stage exchange for infection remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat one-stage exchange, and to investigate the association between the Musculoskeletal Infection Society (MSIS) staging system and further infection-related failure. Methods. We retrospectively reviewed all repeat one-stage revision THAs performed after failed one-stage exchange THA for infection between January 2008 and December 2016. The final cohort included 32 patients. The mean follow-up after repeat one-stage exchange was 5.3 years (1.2 to 13.0). The patients with a further infection-related failure and/or all-cause revision were reported, and Kaplan-Meier survival for these endpoints determined. Patients were categorized according to the MSIS system, and its association with further infection was analyzed. Results. A total of eight repeat septic revisions (25%) developed a further infection-related failure, and the five-year infection-free survival was 81% (95% confidence interval (CI) 57 to 92). Nine (28%) underwent a further all-cause revision and the five-year all-cause revision-free survival was 74% (95% CI 52 to 88). Neither the MSIS classification of the host status (p = 0.423) nor the limb status (p = 0.366) was significantly associated with further infection-related failure. Conclusion. Repeat one-stage exchange for PJI in THA is associated with a favourable five-year infection-free and all-cause revision-free survival. Notably, the rate of infection control is encouraging when compared with the reported rates after repeat two-stage exchange. The results can be used to counsel patients and help clinicians make informed decisions about treatment. With the available number of patients, further infection-related failure was not associated with the MSIS host or limb status. Cite this article: Bone Joint J 2022;104-B(1):27–33

Aims. Periprosthetic hip and knee infection remains one of the most severe complications following arthroplasty, with an incidence between 0.5% to 1%. This study compares the outcomes of revision surgery for periprosthetic joint infection (PJI) following hip and knee arthroplasty prior to and after implementation of a specialist PJI multidisciplinary team (MDT). Methods. Data was retrospectively analyzed from a single centre. In all, 29 consecutive joints prior to the implementation of an infection MDT in November 2016 were compared with 29 consecutive joints subsequent to the MDT conception. All individuals who underwent a debridement antibiotics and implant retention (DAIR) procedure, a one-stage revision, or a two-stage revision for an acute or chronic PJI in this time period were included. The definition of successfully treated PJI was based on the Delphi international multidisciplinary consensus. Results. There were no statistically significant differences in patient demographics or comorbidities between the groups. There was also no significant difference in length of overall hospital stay (p = 0.530). The time taken for formal microbiology advice was significantly shorter in the post MDT group (p = 0.0001). There was a significant difference in failure rates between the two groups (p = 0.001), with 12 individuals (41.38%) pre-MDT requiring further revision surgery compared with one individual (6.67%) post-MDT inception. Conclusion. Our standardized multidisciplinary approach for periprosthetic knee and hip joint infection shows a significant reduction in failure rates following revision surgery. Following implementation of our MDT, our success rate in treating PJI is 96.55%, higher than what current literature suggests. We advocate the role of a specialist infection MDT in the management of patients with a PJI to allow an individualized patient-centred approach and care plan, thereby reducing postoperative complications and failure rates. Cite this article: Bone Jt Open 2021;2(7):509–514

Aim. Periprosthetic joint infections (PJI) are severe complications after total joint arthroplasty (TJA). Up to now, a gold standard in the diagnostics of PJI is missing. Small extracellular vesicles (sEVs) are secreted by all types of cells and play a key role in immune response in presence of infection (1). In this prospective study, the diagnostic accuracy of sEVs in the synovial fluid to detect PJI of knee, hip and shoulder joints was investigated. We hypothesized increased surface markers of sEVs in PJI compared to aseptic complications (e.g. implant loosening, stress shielding related pain). Method. Synovial fluid from 48 patients with painful arthroplasty was examined. The distinction between aseptic and infectious cases was made on the basis of the 2018 Definition of Periprosthetic Hip and Knee Infection (2). 35 (72,9%) probands assigned to aseptic and 13 patients (27,1%) to PJI group. Immuno-fluorescence flow cytometry served to document the concentrations of CD9, CD63, CD66b, CD82 and HLA-DR on sEVs. Results. The concentration of CD9 surface marker on sEVs in synovial fluid was significantly lower (p=0.002) in PJI group than in aseptic group. In contrast, the levels of CD82 on sEVs in synovial fluid was significantly higher (p<0.0001) in the PJI group than in aseptic group. The concentrations of CD63, CD66b and HLA-DR on sEVs in synovial fluid did not differ significantly between the two cohorts (CD63: p=0.372; CD66b: p=0.634; HLA-DR: p=0.558). Conclusions. Overall, the significance of sEVs in the diagnostics of PJI is not well enough understood and the subject of current research and scientific discussion. Our data suggest, that CD82 and CD9 on sEVs in synovial fluid are promising biomarkers to differentiate between PJI and aseptic complications

An increasing elderly population means joint replacement surgery numbers are projected to increase, with associated complications such as periprosthetic joint infections (PJI) also rising. PJI are particularly challenging due to antimicrobial resistant biofilm development on implant surfaces and surrounding tissues, with treatment typically involving invasive surgeries and systemic antibiotic delivery. Consequently, functionalisation of implant surfaces to prevent biofilm formation is a major research focus. This study characterises clinically relevant antimicrobials including gentamicin, clindamycin, daptomycin, vancomycin and caspofungin within a silica-based, biodegradable sol-gel coating for prosthetic devices. Antimicrobial activity of the coatings against clinically relevant microorganisms was assessed via disc diffusion assays, broth microdilution culture methods and the MBEC assay used to determine anti-biofilm activity. Human and bovine cells were cultured in presence of antimicrobial sol-gel to determine cytotoxicity using Alamar blue and antibiotic release was measured by LC-MS. Biodegradability in physiological conditions was assayed by FT-IR, ICP-MS and measuring mass change. Effect of degradation products on osteogenesis were studied by culturing mesenchymal stem cells in the presence of media in which sol-gel samples had been immersed. Antimicrobial-loaded coatings showed strong activity against a wide range of clinically relevant bacterial and fungal pathogens with no loss of activity from antibiotic alone. The sol-gel coating demonstrated controlled release of antimicrobials and initial sol-gel coatings showed no loss of viability on MSCs with gentamicin containing coatings. Current work is underway investigating cytotoxicity of sol-gel compositions against MG-63 cells and primary osteoblasts. This research forms part of an extended study into a promising antimicrobial delivery strategy to prevent PJI. The implant coating has potential to advance PJI infection prevention, reducing future burden upon healthcare costs and patient wellbeing

Aim. The aim of this study was to investigate the metabolomic profile of synovial fluid in periprosthetic joint infection (PJI) cases regarding a possible diagnostic approach. Also, further information about the metabolic composition of synovial fluid in PJI may point to future diagnostic and therapeutic approaches. Method. Patients with a clinical suspicion of a prosthesis infection who underwent a joint puncture in our outpatient department or ward were included. After sample preparation, the nuclear magnetic resonance (NMR) experiments were performed at 310 K on an AVANCE™ NeoBruker Ultrashield 600 MHz spectrometer. Bruker Topspin version 4.0.2 was used for NMR data acquisition. The spectra for all samples were automatically processed (exponential line broadening of 0.3 Hz), phased, and referenced using TSP at 0.0 ppm. In total, 37 metabolites were analysed using a volume of 200 µl per synovial sample. The PJI and aseptic cases were assigned according to the EBJIS criteria. Results. In total, 76 samples were included in the final analysis with 48 PJI cases and 28 aseptic cases. Five measured metabolites have shown an area under the curve (AUC) over 0.8, with Taurine (AUC 0.8558, p<0.0001) and Glutamine (AUC 0.8333, p<0.0001) showing the best diagnostic performance. When combining two metabolites, the AUC indicated even higher diagnostic performance: Glucose/Glycogen (AUC 0.9073, p<0.0001), Taurine/Mannose (AUC 0.9073, p<0.0001), Mannose/Glycogen (AUC 0.8992, p<0.0001) and Taurine/Glucose (AUC 0.8956, p<0.0001). Conclusions. While NMR as a method in PJI diagnostics is currently not broadly available for daily clinical work, our results indicate that certain synovial metabolites and their combinations can be used for PJI diagnosis

Aims. National joint registries under-report revisions for periprosthetic joint infection (PJI). We aimed to validate PJI reporting to the Australian Orthopaedic Association National Joint Arthroplasty Registry (AOANJRR) and the factors associated with its accuracy. We then applied these data to refine estimates of the total national burden of PJI. Methods. A total of 561 Australian cases of confirmed PJI were captured by a large, prospective observational study, and matched to data available for the same patients through the AOANJRR. Results. In all, 501 (89.3%) cases of PJI recruited to the prospective observational study were successfully matched with the AOANJRR database. Of these, 376 (75.0%) were captured by the registry, while 125 (25.0%) did not have a revision or reoperation for PJI recorded. In a multivariate logistic regression analysis, early (within 30 days of implantation) PJIs were less likely to be reported (adjusted odds ratio (OR) 0.56; 95% confidence interval (CI) 0.34 to 0.93; p = 0.020), while two-stage revision procedures were more likely to be reported as a PJI to the registry (OR 5.3 (95% CI 2.37 to 14.0); p ≤ 0.001) than debridement and implant retention or other surgical procedures. Based on this data, the true estimate of the incidence of PJI in Australia is up to 3,900 cases per year. Conclusion. In Australia, infection was not recorded as the indication for revision or reoperation in one-quarter of those with confirmed PJI. This is better than in other registries, but suggests that registry-captured estimates of the total national burden of PJI are underestimated by at least one-third. Inconsistent PJI reporting is multifactorial but could be improved by developing a nested PJI registry embedded within the national arthroplasty registry. Cite this article: Bone Jt Open 2022;3(5):367–373

Aim. Rifampicin as a biofilm-active antibiotic drug has a significant role in the treatment of periprosthetic joint infection (PJI). However, rifampicin resistance is an increasing threat to PJI treatment. This study aimed to evaluate the prevalence of rifampicin resistant staphylococci over time and its association with infection-free survival after PJI in a single centre in Sweden. Methods. We included 238 PJIs in 238 patients who had undergone PJI revision surgery from 2001 to 2020 on whom the causative bacteria were staphylococci, and the agent was tested for rifampicin resistance. Data regarding agents, rifampicin resistance, treatment and outcome was obtained. Kaplan-Meier survival analysis and a Cox regression model with adjustment for age, sex, localisation (hip or knee) and type of prosthesis (primary or revision) were used to calculate infection-free survival rates and adjusted risk ratios (HRs) of the risk of treatment failure. Treatment failure was defined as any reoperation or suppression treatment with antibiotics due to prolonged infection. Results. Among the included 238 PJIs, 40 rifampicin-resistant staphylococci [93% Coagulase Negative Staphylococci (CoNS)] and 29 treatment failures were identified. The proportion of rifampicin resistant agents decreased from 25% in 2010–2015 to 12% in 2016–2020. The 2-year infection-free survival rates were 79.0% (95% CI 0.66–0.92) for the rifampicin resistant and 90% (95% CI 0.86–0.94) for the rifampicin sensitive group. Patients with PJI caused by rifampicin resistant bacteria had a significantly higher risk of treatment failure than those caused by sensitive bacteria (HR 2.5; 95% CI 1.0–6.2). Conclusions. The incidence of PJI caused by rifampicin resistant staphylococci decreased in Uppsala, Sweden over the past 20 years. PJI caused by rifampicin-resistant staphylococci has a two-fold risk for treatment failure compared to PJI caused by rifampicin-sensitive staphylococci, which stresses the importance of retaining rifampicin resistance low. Additionally, the increased risk of treatment failure when PJI is caused by a rifampicin-resistant bacteria warrants consideration of a more conservative treatment strategy

Aims. Single-stage revision total knee arthroplasty (rTKA) is gaining popularity in treating chronic periprosthetic joint infections (PJIs). We have introduced this approach to our clinical practice and sought to evaluate rates of reinfection and re-revision, along with predictors of failure of both single- and two-stage rTKA for chronic PJI. Methods. A retrospective comparative cohort study of all rTKAs for chronic PJI between 1 April 2003 and 31 December 2018 was undertaken using prospective databases. Patients with acute infections were excluded; rTKAs were classified as single-stage, stage 1, or stage 2 of two-stage revision. The primary outcome measure was failure to eradicate or recurrent infection. Variables evaluated for failure by regression analysis included age, BMI, American Society of Anesthesiologists grade, infecting organisms, and the presence of a sinus. Patient survivorship was also compared between the groups. Results. A total of 292 consecutive first-time rTKAs for chronic PJI were included: 82 single-stage (28.1%); and 210 two-stage (71.9%) revisions. The mean age was 71 years (27 to 90), with 165 females (57.4%), and a mean BMI of 30.9 kg/m. 2. (20 to 53). Significantly more patients with a known infecting organism were in the single-stage group (93.9% vs 80.47%; p = 0.004). The infecting organism was identified preoperatively in 246 cases (84.2%). At a mean follow-up of 6.3 years (2.0 to 17.6), the failure rate was 6.1% in the single-stage, and 12% in the two-stage groups. All failures occurred within four years of treatment. The presence of a sinus was an independent risk factor for failure (odds ratio (OR) 4.97; 95% confidence interval (CI) 1.593 to 15.505; p = 0.006), as well as age > 80 years (OR 5.962; 95% CI 1.156 to 30.73; p = 0.033). The ten-year patient survivorship rate was 72% in the single-stage group compared with 70.5% in the two-stage group. This difference was not significant (p = 0.517). Conclusion. Single-stage rTKA is an effective strategy with a high success rate comparable to two-stage approach in appropriately selected patients. Cite this article: Bone Joint J 2021;103-B(8):1373–1379

Abstract. Aims. The primary aim of this study was to evaluate the outcomes of fungal knee periprosthetic joint infection following knee arthroplasty. The secondary aim was to evaluate risk factors for acquiring a fungal PJI. Patients and Methods. This was a retrospective analysis of patients presenting with a confirmed fungal PJI of the knee in two tertiary centres. There were a total of 45 cases. Isolated fungal infections along with mixed bacterial and fungal infections were included. Mean follow up was 40 months (range 3–118). Results. The mean age at presentation was 69 years (range 46 to 87) and mean BMI was 31 kg/m2 (range 20 to 44). The median number of procedures that patients had on the affected limb from the index primary arthroplasty procedure was 6 (range 2–17). The median procedure number at which a fungal infection was identified was 5 (range 2–10). A history of prolonged antibiotic therapy (above 6 months total) was present in 37 patients (88%). During the study period 22 patients were infection free, 14 treated with lifelong suppression, 7 had above knee amputations and 6 had died. Overall infection cure rate was 49%. Conclusions. Patients with fungal PJI are generally poor hosts with multiple co-morbidities, long term exposure to antibiotics and high rates of open wounds and sinuses. The poor outcome associated with fungal PJI relative to bacterial PJI should be shared with patients in order to manage the expectations of this complex cohort

Aims. Despite recent literature questioning their use, vancomycin and clindamycin often substitute cefazolin as the preoperative antibiotic prophylaxis in primary total knee arthroplasty (TKA), especially in the setting of documented allergy to penicillin. Topical povidone-iodine lavage and vancomycin powder (VIP) are adjuncts that may further broaden antimicrobial coverage, and have shown some promise in recent investigations. The purpose of this study, therefore, is to compare the risk of acute periprosthetic joint infection (PJI) in primary TKA patients who received cefazolin and VIP to those who received a non-cephalosporin alternative and VIP. Methods. This was a retrospective cohort study of 11,550 primary TKAs performed at an orthopaedic hospital between 2013 and 2019. The primary outcome was PJI occurring within 90 days of surgery. Patients were stratified into two groups (cefazolin vs non-cephalosporin) based on their preoperative antibiotic. All patients also received the VIP protocol at wound closure. Bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify the odds ratio of PJI. Results. In all, 10,484 knees (90.8%) received cefazolin, while 1,066 knees (9.2%) received a non-cephalosporin agent (either vancomycin or clindamycin) as preoperative prophylaxis. The rate of PJI in the cefazolin group (0.5%; 48/10,484) was significantly lower than the rate of PJI in the non-cephalosporin group (1.0%; 11/1,066) (p = 0.012). After controlling for confounding variables, the odds ratio (OR) of developing a PJI was increased in the non-cephalosporin cohort compared to the cefazolin cohort (OR 2.389; 1.2 to 4.6); p = 0.01). Conclusion. Despite the use of topical irrigant solutions and addition of local antimicrobial agents, the use of a non-cephalosporin perioperative antibiotic continues to be associated with a greater risk of TKA PJI compared to cefazolin. Strategies that increase the proportion of patients receiving cefazolin rather than non-cephalosporin alternatives must be emphasized. Cite this article: Bone Jt Open 2022;3(1):35–41

Aims. Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI. Methods. The study included 48 THAs in 48 patients with a clinical suspicion of PJI, but who did not meet European Bone and Joint Infection Society (EBJIS) PJI criteria preoperatively, out of 105 patients undergoing revision THA at our institution for possible PJI between November 2020 and December 2022. Intraoperatively, synovial fluid calprotectin was measured with LFI. Cases with calprotectin levels ≥ 50 mg/l were considered infected and treated with two-stage revision THA; in negative cases, one-stage revision was performed. At least five tissue cultures were obtained; the implants removed were sent for sonication. Results. Calprotectin was positive (≥ 50 mg/l) in 27 cases; out of these, 25 had positive tissue cultures and/or sonication. Calprotectin was negative in 21 cases. There was one false negative case, which had positive tissue cultures. Calprotectin showed an area under the curve of 0.917, sensitivity of 96.2%, specificity of 90.9%, positive predictive value of 92.6%, negative predictive value of 95.2%, positive likelihood ratio of 10.6, and negative likelihood ratio of 0.04. Overall, 45/48 patients were correctly diagnosed and treated by our algorithm, which included intraoperative calprotectin measurement. This yielded a 93.8% concordance with postoperatively assessed EBJIS criteria. Conclusion. Calprotectin can be a valuable tool in facilitating the intraoperative decision-making process for cases in which chronic PJI is suspected and diagnosis cannot be established preoperatively. Cite this article: Bone Joint J 2024;106-B(5 Supple B):118–124

Aims. The management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is challenging. The correct antibiotic management remains elusive due to differences in epidemiology and resistance between countries, and reports in the literature. Before the efficacy of surgical treatment is investigated, it is crucial to analyze the bacterial strains causing PJI, especially for patients in whom no organisms are grown. Methods. A review of all revision TKAs which were undertaken between 2006 and 2018 in a tertiary referral centre was performed, including all those meeting the consensus criteria for PJI, in which organisms were identified. Using a cluster analysis, three chronological time periods were created. We then evaluated the antibiotic resistance of the identified bacteria between these three clusters and the effectiveness of our antibiotic regime. Results. We identified 129 PJIs with 161 culture identified bacteria in 97 patients. Coagulase-negative staphylococci (CNS) were identified in 46.6% cultures, followed by Staphylococcus aureus in 19.8%. The overall resistance to antibiotics did not increase significantly during the study period (p = 0.454). However, CNS resistance to teicoplanin (p < 0.001), fosfomycin (p = 0.016), and tetracycline (p = 0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and was the most effective agent. Conclusion. Although we were unable to show an overall increase in antibiotic resistance in organisms that cause PJI after TKA during the study period, this was not true for CNS. It is concerning that resistance of CNS to new antibiotics, but not vancomycin, has increased in a little more than a decade. Our findings suggest that referral centres should continuously monitor their bacteriological analyses, as these have significant implications for prophylactic treatment in both primary arthroplasty and revision arthroplasty for PJI. Cite this article: Bone Joint J 2021;103-B(6 Supple A):171–176

Aim. Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty. While research has focused on developing better tests for disease diagnosis, treatment options have stayed relatively constant over the years with high failure rates ranging from 30%–50% and are due in part to the protective biofilm produced by some bacterial species. Current treatment options are compromised by the presence of biofilm, emphasizing the need for novel treatment strategies to be developed. Our group has developed a novel treatment (PhotothermAA) which has demonstrated in vitro its ability to target bacterial biofilm. The purpose of this study was to test this PhotothermAA technology in vivo in a rabbit model of PJI for its efficacy in eradicating biofilm. Method. Rabbits were fitted with a titanium implant into the tibial plateau and inoculated with 5×10. 6. CFU Xen36 (luminescent Staphylococcus aureus). At two weeks, rabbits underwent irrigation and debridement and treatment with PhotothermAA gel for two hours and subsequently laser heated using an 808 nm laser for 10 minutes. Gel was washed out and implant was removed for quantitative biofilm coverage analysis via scanning electron microscopy (SEM, n=3 for control and n=2 for PhotothermAA treated). Periprosthetic tissue was collected before and after treatment for toxicity studies via hemotoxylin and eosin (H&E) staining and scored for necrosis by three blinded reviewers (n=5 per group). Student's t-test was used for statistical analysis. Results. Implants isolated after PhotothermAA gel treatment had less biofilm coverage on the surface of the implant compared to non-treated control via SEM analysis (36.9% vs. 55.2%, p<0.14). PhotothermAA gel treatment and subsequent laser treatment was not harmful to surrounding tissue as no increase in necrotic tissue was observed. Conclusions. PhotothermAA gel and laser treatment safely decreases biofilm coverage on infected knee implants in a rabbit PJI model

Background. Periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) is a severe complication in terms of disability, morbidity, and cost. We performed a study to investigate whether early PJI (within 90 days of primary TKA) is associated with increased mortality. Secondary aims were to compare mortality rates over time and between surgical treatment methods. Methods. Patients with suspected PJI were identified by linkage of the Swedish Knee Arthroplasty Register (SKAR) and the Swedish Prescribed Drug Register (SPDR) in 2007–2008 and 2012–2013. Medical records of patients receiving more than 4 weeks of continuous antibiotic therapy were subsequently reviewed to verify the PJI diagnosis. Information on mortality was obtained through the SKAR which is updated daily from the tax agency and patients with PJI were compared to patients without PJI. Results. 466 patients were diagnosed with PJI within 90 days and compared to 40,362 patients without PJI. Mortality rates were significantly higher for PJI patients in both short- and long term: 2.6% vs. 0.8% at 1 year, 4.9% vs. 1.9% at 2 years, 15.7% vs. 7.1% at 5 years, and 38% vs. 21.4% at 10 years. The difference in mortality rate remained after adjusting for sex, age, diagnosis, and time period for surgery with Hazard Ratio 1.8 (95% CI:1.6–2.1). Mortality rates did not differ between time periods, and we found no correlation to surgical treatment. Conclusion. Patients with early PJI after primary TKA have an increased mortality rate compared to TKA patients without PJI. Improvements in surgical treatment strategy has not resulted in better survival. Long term difference in mortality rates indicates that PJI is not the sole reason for mortality suggesting a general frailty in PJI patients

Aims. Periprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large animal models necessary for testing and validating new treatment strategies for these conditions are lacking. The purpose of this study was to develop a rabbit model of chronic PJI in the distal femur. Methods. Fresh suspensions of Staphylococcus aureus (ATCC 25923) were prepared in phosphate-buffered saline (PBS) (1 × 10. 9. colony-forming units (CFUs)/ml). Periprosthetic osteomyelitis in female New Zealand white rabbits was induced by intraosseous injection of planktonic bacterial suspension into a predrilled bone tunnel prior to implant screw placement, examined at five and 28 days (n = 5/group) after surgery, and compared to a control aseptic screw group. Radiographs were obtained weekly, and blood was collected to measure ESR, CRP, and white blood cell (WBC) counts. Bone samples and implanted screws were harvested on day 28, and processed for histological analysis and viability assay of bacteria, respectively. Results. Intraosseous periprosthetic introduction of planktonic bacteria induced an acute rise in ESR and CRP that subsided by day 14, and resulted in radiologically evident periprosthetic osteolysis by day 28 accompanied by elevated WBC counts and histological evidence of bacteria in the bone tunnels after screw removal. The aseptic screw group induced no increase in ESR, and no lysis developed around the implants. Bacterial viability was confirmed by implant sonication fluid culture. Conclusion. Intraosseous periprosthetic introduction of planktonic bacteria reliably induces survivable chronic PJI in rabbits. Cite this article: Bone Joint Res 2021;10(3):156–165

Aim. A large body of evidence is emerging to implicate that dysregulation of the gut microbiome (dysbiosis) increases the risk of surgical site infections. Gut dysbiosis is known to occur in patients with inflammatory bowel disease (IBD), allowing for translocation of bacteria across the inflamed and highly permeable intestinal mucosal wall. The null hypothesis was that IBD was not associated with increased risk of periprosthetic joint infection (PJI) after primary total hip and knee arthroplasty. Our aim was to investigate whether a prior diagnosis of IBD was associated with a higher risk of PJI following primary total hip and knee arthroplasty. Method. A matched cohort study was designed. Primary endpoint was the occurrence of PJI at 2-year. Secondary endpoints were aseptic revisions, as well as discharge to rehab facility, complications up to 30 days, and readmission up to 90 days after TJA. ICD-9 and −10 codes were used to identify patients with IBD and the control cohort. A chart review was performed to confirm diagnosis of IBD. Using our institutional database, 154 patients with IBD were identified and matched (3 to 1) for age, sex, body mass index (BMI), year of surgery, and joint affected with 462 individuals without IBD undergoing TJA. Results. The cumulative incidence of PJI was 4.55% among patients with IBD versus 1.32% among the control cohort (p=0.024). When bivariate logistic regression was performed, a diagnosis of IBD was found to be an independent risk factor for PJI (OR 3.56 95% C.I. 1.17 – 11.23; p=0.024) and aseptic revisions (OR 3.47, 95% C.I. 1.30 – 3.47; p=0.012). The rate of postoperative complications was also higher in patients with IBD. Conclusions. Based on the findings of this study, it appears that patients with IBD are at higher risk for failure due to PJI or aseptic loosening after TJA. The exact reason for this finding is not known but could be related to the bacterial translocation from the inflamed intestinal mucosa, the dysregulated inflammatory status of these patients, malnutrition, and potentially other factors. Some of the so-called aseptic failures maybe also as a result of infection that may have escaped detection and/or recognition

Aims. Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI. Methods. A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared. Results. Using the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001). Conclusion. With high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods. Cite this article: Bone Joint Res 2021;10(8):536–547

Aim. It is traditionally stated that around 80% of all periprosthetic joint infections (PJI) are caused by well-known gram-positive organisms such as Staphylococcus aureus. With the advances in diagnostic modalities and improved abilities to isolate infective organisms, we believe the organism profile causing PJI has changed over time and includes numerous other organisms that were either not recognized as pathogens and/or considered as contaminants. Method. We retrospectively reviewed the medical records of 1,363 patients with confirmed PJI (559 THA and 804 TKA) who received treatment at our institution between 2000 and 2019. Pertinent data related to demographics, microbiological findings, and outcome of treatment were collected. Organisms were differentiated using culture or confirmed by Matrix-Assisted Laser Desorption Ionization-time of flight (MALDI-tof) mass spectrometry. Statistical analysis included logistic regressions. Results. There was a total of 26 different species of organisms that resulted in PJI in our cohort. The rate of PJI caused by slow growing organisms, that are catalase negative, such as Streptococcal viridans (OR 1.244; 95% CI 1.036–1.494), Streptococcus agalactiae (OR 1.513; 95% CI 1.207–1.898), and Staphylococcus epidermidis (OR 1.321; 95% CI 1.191–1.466) has been increasing over time. In contrast, the incidence of PJI caused by coagulase-negative Staphylococcus (OR 0.954; 95% CI 0.927–0.981); resistant species (OR 0.962, 95% CI 0.931–0.995), and Gram-positive species (OR 0.94, 95% CI 0.914–0.966) decreased over time. Notably, there was a higher prevalence of Streptococcal PJI (OR 0.551, 95% CI 0.374–0.812) and culture-negative PJI (OR 0.652, 95% CI 0.478–0.890) seen in knees versus hips. The rate of culture negative PJI also increased from 20% in 2000 to 28% in 2019. In the latter years of the study, very unusual list of organisms causing PJI were also identified. Conclusions. This study reveals that the list of organisms causing PJI has expanded in recent years. The study also finds that some the slow growing organisms that were previously believed to be “contaminants” can and do cause PJI in a considerable number of patients. The number of culture negative cases of PJI has also increased at our institution over the years. There are a number of explanations for the latter finding, perhaps with the most important reason being liberal use of antibiotics that interferes with isolation of the infective organism

Aims. The aim of this meta-analysis is to assess the association between exchange of modular parts in debridement, antibiotics, and implant retention (DAIR) procedure and outcomes for hip and knee periprosthetic joint infection (PJI). Methods. We conducted a systematic search on PubMed, Embase, Web of Science, and Cochrane library from inception until May 2021. Random effects meta-analyses and meta-regression was used to estimate, on a study level, the success rate of DAIR related to component exchange. Risk of bias was appraised using the (AQUILA) checklist. Results. We included 65 studies comprising 6,630 patients. The pooled overall success after DAIR for PJI was 67% (95% confidence interval (CI) 63% to 70%). This was 70% (95% CI 65% to 75%) for DAIR for hip PJI and 63% (95% CI 58% to 69%) for knee PJI. In studies before 2004 (n = 27), our meta-regression analysis showed a 3.5% increase in success rates for each 10% increase in component exchange in DAIR for hip PJI and a 3.1% increase for each 10% increase in component exchange for knee PJI. When restricted to studies after 2004 (n = 37), this association changed: for DAIR for hip PJI a decrease in successful outcome by 0.5% for each 10% increase in component exchange and for DAIR for knee PJI this was a 0.01% increase in successful outcome for each 10% increase in component exchange. Conclusion. This systematic review and meta-regression found no benefit of modular component exchange on reduction of PJI failure. This limited effect should be weighed against the risks for the patient and cost on a case-by-case basis. The association between exchange of modular components and outcome changed before and after 2004. This suggests the effect seen after 2004 may reflect a more rigorous, evidence-based, approach to the infected implant compared to the years before. Level of Evidence: Level III. Cite this article: Bone Jt Open 2021;2(10):806–812

Aims. We aimed to evaluate the utility of . 68. Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with . 99m. Tc-methylene bisphosphonates (. 99m. Tc-MDP) bone scan. Methods. We studied 39 patients with suspected PJI or AL. These patients underwent . 68. Ga-citrate PET/CT, . 99m. Tc-MDP three-phase bone scan and single-photon emission CT (SPECT)/CT. PET/CT was performed at ten minutes and 60 minutes after injection, respectively. Images were evaluated by three nuclear medicine doctors based on: 1) visual analysis of the three methods based on tracer uptake model, and PET images attenuation-corrected with CT and those not attenuation-corrected with CT were analyzed, respectively; and 2) semi-quantitative analysis of PET/CT: maximum standardized uptake value (SUVmax) of lesions, SUVmax of the lesion/SUVmean of the normal bone, and SUVmax of the lesion/SUVmean of the normal muscle. The final diagnosis was based on the clinical and intraoperative findings, and histopathological and microbiological examinations. Results. Overall, 23 and 16 patients were diagnosed with PJI and AL, respectively. The sensitivity and specificity of three-phase bone scan and SPECT/CT were 100% and 62.5%, 82.6%, and 100%, respectively. Attenuation correction (AC) at 60 minutes and non-AC at 60 minutes of PET/CT had the same highest sensitivity and specificity (91.3% and 100%), and AC at 60 minutes combined with SPECT/CT could improve the diagnostic efficiency (sensitivity = 95.7%). Diagnostic efficacy of the SUVmax was low (area under the curve (AUC) of ten minutes and 60 minutes was 0.814 and 0.806, respectively), and SUVmax of the lesion/SUVmean of the normal bone at 60 minutes was the best semi-quantitative parameter (AUC = 0.969). Conclusion. 68. Ga-citrate showed the potential to differentiate PJI from AL, and visual analysis based on uptake pattern of tracer was reliable. The visual analysis method of AC at 60 minutes, combined with . 99m. Tc-MDP SPECT/CT, could improve the sensitivity from 91.3% to 95.7%. In addition, a major limitation of our study was that it had a limited sample size, and more detailed studies with a larger sample size are warranted. Cite this article: Bone Joint Res 2022;11(6):398–408

Aim. This study assesses the ability of the JS-BACH classification of bone infection to predict clinical and patient-reported outcomes in prosthetic joint infection (PJI). Method. Patients who received surgery for suspected PJI at two specialist bone infection centres within the UK between 2010 and 2015 were classified using the JS-BACH classification into either ‘uncomplicated’, ‘complex’ or ‘limited options’. All patients were classified by two clinicians blinded to outcome, with any discrepancies adjudicated by a third reviewer. At the most recent follow-up, patients were assessed for (i) any episode of recurrence since the index operation and (ii) the status of the joint. A Cox proportional-hazard model assessed significant predictors of recurrence following the index procedure. Patient-reported outcomes included the EuroQol EQ-5D-3L index score and the EQ-visual analogue score (VAS) at 0, 14, 42, 120 and 365 days following the index operation. Results. 220 patients met the inclusion criteria during the study period which included PJI of the knee (n=111), hip (n=102), shoulder (n=4) and elbow (n=3). The median time to final follow-up was 4.7 years (inter-quartile range 2.7 – 6.7 years). Controlling for type of index procedure and site of infection, Cox proportional-hazards ratio of recurrence when being classified as complex versus uncomplicated was 25.2 (95% CI 3.45 – 183.7, p<0.001) and having limited options verses uncomplicated was 59.0 (95% CI 7.93 – 439.1, p<0.001). None of the patients who were classified as ‘uncomplicated’ PJI (0/52) had received either amputation, joint fusion, excision arthroplasty, chronic suppressive anti-biotics, had died from sepsis secondary to PJI or were awaiting treatment for an active infection at final follow-up. This compared to 21.3% (27/127) of patients classified as ‘complex’ PJI and 65.9% (27/41) of patients classified as ‘limited options’. Compared to the age-matched population, patients with ‘uncomplicated’ PJI reported similar EQ-index scores (age-matched population: 0.782, ‘uncomplicated’: 0.730, SD 0.326) and EQ-VAS (age-matched: 77.9, ‘uncomplicated’ PJI: 79.4, SD 20.9). This was significantly higher when compared to patients classified as ‘complex’ (EQ-index: 0.515 SD 0.323, p<0.012; EQ-VAS: 68.4 SD 19.4, p=0.042) and ‘limited options’ (EQ-index: 0.333 SD 0.383, p<0.001; EQ-VAS: 60.2, SD 23.1, p=0.005, ANOVA with Tukey post-hoc comparison). Conclusions. We have demonstrated that the JS-BACH classification for bone and joint infection is a significant predictor of clinical outcome and quality of life following surgery for PJI. This will allow clinicians to offer prognostic information to patients and guide the timing of referral for specialist management in PJI

Aims. Use of molecular sequencing methods in periprosthetic joint infection (PJI) diagnosis and organism identification have gained popularity. Next-generation sequencing (NGS) is a potentially powerful tool that is now commercially available. The purpose of this study was to compare the diagnostic accuracy of NGS, polymerase chain reaction (PCR), conventional culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al in the diagnosis of PJI. Methods. In this retrospective study, aspirates or tissue samples were collected in 30 revision and 86 primary arthroplasties for routine diagnostic investigation for PJI and sent to the laboratory for NGS and PCR. Concordance along with statistical differences between diagnostic studies were calculated. Results. Using the MSIS criteria to diagnose PJI as the reference standard, the sensitivity and specificity of NGS were 60.9% and 89.9%, respectively, while culture resulted in sensitivity of 76.9% and specificity of 95.3%. PCR had a low sensitivity of 18.4%. There was no significant difference based on sample collection method (tissue swab or synovial fluid) (p = 0.760). There were 11 samples that were culture-positive and NGS-negative, of which eight met MSIS criteria for diagnosing infection. Conclusion. In our series, NGS did not provide superior sensitivity or specificity results compared to culture. PCR has little utility as a standalone test for PJI diagnosis with a sensitivity of only 18.4%. Currently, several laboratory tests for PJI diagnosis should be obtained along with the overall clinical picture to help guide decision-making for PJI treatment. Cite this article: Bone Joint J 2021;103-B(1):26–31

Aim. We aimed to evaluate the impact of knee periprosthetic joint infection (PJI) by assessing the patients’ long-term quality of life and explicitly their psychological wellbeing after successful treatment. Method. Thirty-six patients with achieved eradication of infection after knee PJI were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data. Results. At a follow-up of 4.9± 3.5 years the mean SF-36 score was 24.82± 10.0 regarding the physical health component and 46.16± 13.3 regarding the mental health component compared to German normative values of 48.36± 9.4 (p< .001) and 50.87± 8.8 (p= .003). The mean EQ-5D index reached 0.55± 0.33 with an EQ-5D VAS rating of 52.14± 19.9 compared to reference scores of 0.891 (p< .001) and 68.6± 1.1 (p< .001). Mean scores of the ISR revealed psychological symptom burden on the depression scale. Conclusions. PJI patients still suffer from significant lower quality of life compared to normative data even years after surgically successful treatment. Future clinical studies should focus on patient-related outcome measures. Newly emerging treatment strategies, prevention methods and interdisciplinary approaches should be implemented to improve the quality of life of PJI patients

Aims. Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). Methods. A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. Results. The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. Conclusion. In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue. Cite this article: Bone Joint Res 2024;13(7):332–341

Objectives. The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. Methods. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Results. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Conclusion. Our review helped to identify factors that can influence serum biomarkers’ level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis. Cite this article: A. Saleh, J. George, M. Faour, A. K. Klika, C. A. Higuera. Serum biomarkers in periprosthetic joint infections. Bone Joint Res 2018;7:85–93. DOI: 10.1302/2046-3758.71.BJR-2017-0323

Aims. Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model. Methods. Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation. Results. Rats receiving intra-articular vancomycin showed the best outcomes among the four treatment groups, with negative bacterial cultures, increased weight gain, increased capacity for weightbearing activities, increased residual bone volume preservation, and reduced inflammatory reactions in the joint tissues, indicating MRSA eradication in the knee. The vancomycin-spacer and/or systemic vancomycin failed to eliminate the MRSA infections following a two-week antibiotic course. Serum vancomycin levels did not reach nephrotoxic levels in any group. Mild renal histopathological changes, without changes in serum creatinine levels, were observed in the intraperitoneal vancomycin group compared with the intra-articular vancomycin group, but no changes in hepatic structure or serum alanine aminotransferase or aspartate aminotransferase levels were observed. No local complications were observed, such as sinus tract or non-healing surgical incisions. Conclusion. Intra-articular vancomycin injection was effective and safe for PJI control following debridement and spacer implantation in a rat model during two-stage revision arthroplasties, with better outcomes than systemic vancomycin administration. Cite this article: Bone Joint Res 2022;11(6):371–385

Aims. Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 10. 5. colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log. 10. (95%) and 1.5-log. 10. (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 10. 3. vs 7.0 × 10. 4. ; p = 0.022; 3.6 × 10. 3. vs 1.0 × 10. 5. ; p = 0.007, respectively) at POD 21. There was a significant 1.6-log. 10. (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 10. 0. vs 4.7 × 10. 1. , respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections. Cite this article: Bone Joint J 2024;106-B(6):632–638

Aims. To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI). Methods. A retrospective cohort study of 50 chronic kPJI patients treated with two types of articulating spacers between January 2014 and March 2022 was conducted. The clinical outcomes and functional status of the different articulating spacers were compared. Overall, 17 patients were treated with prosthetic spacers (prosthetic group (PG)), and 33 patients were treated with cement spacers (cement group (CG)). The CG had a longer mean follow-up period (46.67 months (SD 26.61)) than the PG (24.82 months (SD 16.46); p = 0.001). Results. Infection was eradicated in 45 patients overall (90%). The PG had a better knee range of motion (ROM) and Knee Society Score (KSS) after the first-stage revision (p = 0.004; p = 0.002), while both groups had similar ROMs and KSSs at the last follow-up (p = 0.136; p = 0.895). The KSS in the CG was significantly better at the last follow-up (p = 0.013), while a larger percentage (10 in 17, 58.82%) of patients in the PG chose to retain the spacer (p = 0.008). Conclusion. Prosthetic spacers and cement spacers are both effective at treating chronic kPJI because they encourage infection control, and the former improved knee function status between stages. For some patients, prosthetic spacers may not require reimplantation. Cite this article: Bone Joint Res 2024;13(6):306–314

Aims. Periprosthetic joint infection (PJI) is a debilitating condition with a substantial socioeconomic burden. A novel autologous blood glue (ABG) has been developed, which can be prepared during surgery and sprayed onto prostheses at the time of implantation. The ABG can potentially provide an antimicrobial coating which will be effective in preventing PJI, not only by providing a physical barrier but also by eluting a well-known antibiotic. Hence, this study aimed to assess the antimicrobial effectiveness of ABG when impregnated with gentamicin and stem cells. Methods. Gentamicin elution from the ABG matrix was analyzed and quantified in a time-dependent manner. The combined efficiency of gentamicin and ABG as an anti-biofilm coating was investigated on titanium disks. Results. ABG-gentamicin was bactericidal from 10 μg/ml and could release bactericidal concentrations over seven days, preventing biofilm formation. A concentration of 75 μg/ml of gentamicin in ABG showed the highest bactericidal effect up to day 7. On titanium disks, a significant bacterial reduction on ABG-gentamicin coated disks was observed when compared to both uncoated (mean 2-log reduction) and ABG-coated (mean 3-log reduction) disks, at days 3 and 7. ABG alone exhibited no antimicrobial or anti-biofilm properties. However, a concentration of 75 μg/ml gentamicin in ABG sustains release over seven days and significantly reduced biofilm formation. Its use as an implant coating in patients with a high risk of infection may prevent bacterial adhesion perioperatively and in the early postoperative period. Conclusion. ABG’s use as a carrier for stem cells was effective, as it supported cell growth. It has the potential to co-deliver compatible cells, drugs, and growth factors. However, ABG-gentamicin’s potential needs to be further justified using in vivo studies. Cite this article: Bone Joint Res 2020;9(12):848–856

Aim. To assess whether recurrence of PJI and osteomyelitis impacts patient-reported quality of life (QoL). Method. We studied patients receiving surgical treatment for confirmed PJI or osteomyelitis in one of 26 centres in the UK. Patients completed the EQ-5D-3L questionnaire, directly after surgery, at day 14, day 42, day 120 and day 365 after surgery and were assessed for evidence of recurrence. Results. Of 621 patients with PJI, 99 had recurrent infection (15.9%). Patients with recurrence reported significantly lower QoL at one year after surgery compared to those without recurrence (EQ-5D-3L index score with recurrence: 0.368, SD0.344 vs. no recurrence: 0.592, SD0.315, p<0.001). Patients were grouped based on the timing of their recurrence: <42 days (n=27); 42–120 (n=28); or >120 days (n=44) post-surgery. At the time-point immediately preceding the diagnosis of recurrence, QoL was significantly lower than in corresponding patients without recurrence (recurrence <42 days, p<0.05; 42–120 days, p<0.001; >120 days, p<0.05). In 358 cases of osteomyelitis, 39 patients had recurrent infection (10.9%). Recurrence of osteomyelitis produced significantly lower QoL at one year after surgery compared to patients without recurrent infection (EQ-5D-3L for recurrence: 0.385, SD0.345 vs. no recurrence: 0.634, SD0.349, p<0.001). Patients with recurrence after 120 days (n=21) reported significantly lower QoL than those with no recurrence at the time-point immediately preceding the diagnosis of recurrence (p<0.01). In contrast to patients with PJI, patients with osteomyelitis who had recurrence diagnosed before 120 days (n=18) reported similar outcome scores to patients who did not have recurrence. Conclusion. Failure to eradicate infection greatly affects patient QoL. This study supports the monitoring of EQ-5D-3L among patients treated for bone and joint infections; patients with poorer QoL at follow up should prompt a low threshold for investigation to assess whether recurrence or continued infection is the underlying cause

Aims. Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition. Methods. A retrospective analysis included 78 PJI patients (29 hips; 49 knees) who had undergone multiple prior surgical interventions. Our cohort was treated with single-stage revision using a supplementary intra-articular antibiotic infusion. Of these 78 patients, 59 had undergone more than two prior failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, three hips had previously undergone failed two-stage revision, and four had a failed one-stage revision before their single-stage revision. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, an intra-articular infusion of vancomycin, imipenem, or voriconazole was performed postoperatively. The antibiotic solution was soaked into the joint for 24 hours for a mean of 16 days (12 to 21), then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated. Results. A total of 68 patients (87.1%) were free of infection at a mean follow-up time of 85 months (24 to 133). The seven-year infection-free survival was 87.6% (95% confidence interval (CI) 79.4 to 95.8). No significant difference in infection-free survival was observed between hip and knee PJIs (91.5% (95% CI 79.9 to 100) vs 84.7% (95% CI 73.1 to 96.3); p = 0.648). The mean postoperative Harris Hip Score was 76.1 points (63.2 to 92.4) and Hospital for Special Surgery score was 78. 2 (63.2 to 92.4) at the most recent assessment. Polymicrobial and fungal infections accounted for 14.1% (11/78) and 9.0% (7/78) of all cases, respectively. Conclusion. Single-stage revision with intra-articular antibiotic infusion can provide high antibiotic concentration in synovial fluid, thereby overcoming reduced vascular supply and biofilm formation. This supplementary route of administration may be a viable option in treating PJI after multiple failed prior surgeries for reinfection. Cite this article: Bone Joint J 2022;104-B(7):867–874

Aims. Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity. Methods. We retrospectively reviewed 32 patients (22 hips and 11 knees) who underwent single-stage revision combined with IA carbapenem infusion between November 2013 and March 2020. The IA and intravenous (IV) carbapenem infusions were administered for a single Gram-negative infection, and IV vancomycin combined with IA carbapenems and vancomycin was applied for polymicrobial infection including Gram-negative bacteria. The bacterial community distribution, drug sensitivity, infection control rate, functional recovery, and complications were evaluated. Reinfection or death caused by PJI was regarded as a treatment failure. Results. Gram-negative PJI was mainly caused by Escherichia coli (8/34), Enterobacter cloacae (7/34), and Klebsiella pneumoniae (5/34). Seven cases (7/32) involved polymicrobial PJIs. The resistance rates of penicillin, cephalosporin, quinolones, and sulfonamides were > 10%, and all penicillin and partial cephalosporins (first and second generation) were > 30%. Of 32 cases, treatment failed to eradicate infection in only three cases (9.4%), at a mean follow-up of 55.1 months (SD 25 to 90). The mean postoperative Harris Hip Score and Hospital for Special Surgery knee score at the most recent follow-up were 81 (62 to 91) and 79 (56 to 89), respectively. One patient developed a fistula, and another presented with a local rash on an infected joint. Conclusion. The use of IA carbapenem delivered alongside one-stage revision effectively controlled Gram-negative infection and obtained acceptable clinical outcomes with few complications. Notably, first- and second-generation cephalosporins and penicillin should be administrated with caution, due to a high incidence of resistance. Cite this article: Bone Joint J 2023;105-B(3):284–293

Objectives. Periprosthetic joint infection following joint arthroplasty surgery is one of the most feared complications. The key to successful revision surgery for periprosthetic joint infections, regardless of treatment strategy, is a thorough deep debridement. In an attempt to limit antimicrobial and disinfectant use, there has been increasing interest in the use of acetic acid as an adjunct to debridement in the management of periprosthetic joint infections. However, its effectiveness in the eradication of established biofilms following clinically relevant treatment times has not been established. Using an in vitro biofilm model, this study aimed to establish the minimum biofilm eradication concentration (MBEC) of acetic acid following a clinically relevant treatment time. Materials and Methods. Using a methicillin-sensitive Staphylococcus aureus (MSSA) reference strain and the dissolvable bead assay, biofilms were challenged by 0% to 20% acetic acid (pH 4.7) for ten minutes, 20 minutes, 180 minutes, and 24 hours. Results. The MBEC of acetic acid was found to be: 15%, 11%, 3.2%, and 0.8% following a ten-minute, 20-minute, 180-minute, and 24-hour treatment, respectively. Conclusion. This study found that the MBEC of acetic acid following a 10- or 20-minute treatment time exceeded its safety threshold, making these concentrations unsuitable as a topical debridement adjunct. However, a clinically acceptable concentration (5%) was still found to eliminate 96.1% of biofilm-associated MSSA following a 20-minute treatment time. Cite this article: S. T. J. Tsang, P. J. Gwynne, M. P. Gallagher, A. H. R. W. Simpson. The biofilm eradication activity of acetic acid in the management of periprosthetic joint infection. Bone Joint Res 2018;7:517–523. DOI: 10.1302/2046-3758.78.BJR-2018-0045.R1

Aim. The number of periprosthetic joint infections (PJI) is increasing due to ageing population and increasing numbers of arthroplasty procedures and treatment is costly. Aim of the study was to analyze the direct healthcare costs of PJI in Europe for total hip arthroplasties (THA) and total knee arthroplasties (TKA). Method. A systematic review in PubMed with search of direct costs of PJI in European countries was performed. Thereby the term cost* AND (infection OR PJI) AND (prosthesis OR knee OR hip OR “TKA” OR “THA” OR arthroplast*) was combined with each European country to detect relevant publications. Publications with definition of performed procedure and joint localization were included into further analysis. The mean value of direct healthcare cost was calculated for the respective joint and the respective operation performed. Results. Screening revealed 1,274 eligible publications. After review of abstracts and full-texts n=11 manuscripts were included into final analysis (Figure 1). The mean combined direct hospital costs for revision for PJI after TKA and THA was 26,311€. Mean costs for revision procedures for PJI after TKA were 24,617€. Direct costs for TKA-PJI treated with debridement, antibiotics and implant retention (DAIR) were on average 10,121€. For two-stage revisions in knee arthroplasties total average costs were 30,829€. Referring to revision surgery for PJI in THA, the mean hospital costs in Europe were 28,005€. For a DAIR procedure direct healthcare costs of 5,528€ were identified. Two-stage revision cost on average 31,217€. Conclusions. PJIs are associated with significant direct healthcare costs. The financial burden of up to 30,000 € per case underlines the impact of the disease for European health care system. However, the number of detailed reports on PJI costs is limited and the quality of the literature is limited. There is a strong need for more detailed financial data on the costs of PJI treatment. For any tables or figures, please contact the authors directly

Aim. Apart from other biomarkers isolated in the synovial fluid, alpha-defensin appears to be a promising diagnostic tool to confirm a periprosthetic joint infection (PJI) in the hip or knee. The purpose of this study was to evaluate the sensitivity and specificity of an alpha defensin lateral flow (ADLF) test compared to usual standard classifications in the diagnostic management of PJI. Method. This investigation was set up as a multicenter prospective cohort study. Synovial fluid was obtained by means of joint aspiration or intra-operative tissue biopsies. A presumptive PJI diagnosis was made according to criteria outlined by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA) and the European Bone and Joint Infection Society (EBJIS). The intention to treat by the surgeon was logged. Sensibility and specificity for the ADLF test was plotted for each aforementioned diagnostic algorithm. Spearman correlations between all scores were analyzed. Multiple logistic regression was used to determine the contribution of independent variables to the probability of PJI. Results. Hundred thirty-six patients with a painful arthroplasty were assessed for infection and rated by the treating surgeon as potentially infected or not on the basis of clinical and laboratory information. According to the EBJIS criteria sixty-eight patients were deemed infected, fifty according to the IDSA criteria, forty-one according to the MSIS criteria and forty according to the ADLF test. However, the sensitivity of ADLF test was 87.8% for MSIS, 70% for IDSA and 55.8% for EBJIS. The specificity of ADLF test was between 94% – 97%. Good correlation was observed between synovial fluid culture and ADLF test (r = 0.73). Low to excellent correlations between the ADLF test and the EBJIS (r = 0.58), IDSA (r = 0.68), and MSIS score (r = 0.84) were observed. The surgeon's intention to treat correlated well with the MSIS score (r = 0.86), and moderately with the EBJIS (r = 0.59). Conclusions. ADLF test sensibility was variable, but its specificity was excellent. Most of the cases, not retained by MSIS but classified by EBJIS as infected, got a negative microbiological result. Considering an accepted 20% negative microbiological result rate in PJI diagnostic, EBJIS is clearly overestimating the number of infected cases. MSIS score correlates with the surgeon intention to treat and ADLF test

Aim. The current antibiotic treatment of periprosthetic joint infection (PJI) is optimized by measuring concentrations in plasma. However, it remains unclear whether effective concentrations of the antibiotics are reached at the site of PJI. Nonetheless, adequate target site concentrations are important to achieve effective eradication of the micro-organism. In order to determine the efficacy of cefuroxime and flucloxacillin in synovial fluid, synovial tissue and bone tissue in relation to the minimal inhibitory concentration (MIC) of the pathogen causing the PJI, we perform a pharmacokinetic/pharmacodynamic (PK/PD) study. Therefore, we aimed to develop validated analytical methods for analysis of cefuroxime and flucloxacillin in synovial fluid, synovial tissue and bone tissue. Method. Blank samples of synovial fluid, synovial tissue and bone tissue were obtained by orthopedic surgeons during surgery. For validation the samples of each matrix were spiked with both cefuroxime and flucloxacillin. Synovial tissue and bone tissue was pulverized with a mikro-dismembrator. Samples were kept frozen at −20°C until analysis. After a sample preparation quantification of cefuroxime and flucloxacillin in each matrix was performed on the ultra-performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS). Stable-isotope-labeled meropenem-d6 served as internal standard. The linearity, limits of quantification, accuracy and precision and carry-over were determined for all methods separately. The methods were validated according to the European Medicine Agency (EMA) and Food and Drug Administration (FDA) guidelines on bioanalytical method validation. Results. These methods were successfully validated for cefuroxime and flucloxacillin quantification in all matrices according to the EMA and FDA guidelines. The limits of quantification were adequate to cover potential cefuroxime and flucloxacillin concentration in synovial fluid, synovial tissue and bone tissue as described in literature, with a range of 1–100mg/L for synovial fluid and 1–20 µg/g for synovial tissue and bone tissue (r >0.995). Accuracy and within-run precision were validated according to acceptance values (RSD <15%). Carry over was less than 20%. Matrix effects and recovery were investigated for synovial fluid. The results were within the range of 80–120%. Conclusions. The results of the validation fall within the limits of quantification according to the EMA and FDA guidelines. Therefore, these methods can be applied during a PK/PD study to discover the exposure of antibiotics in synovial fluid, synovial tissue and bone tissue at the site of infection in patients with a PJI

Aims. The aim of this study was to estimate the 90-day periprosthetic joint infection (PJI) rates following total knee arthroplasty (TKA) and total hip arthroplasty (THA) for osteoarthritis (OA). Methods. This was a data linkage study using the New South Wales (NSW) Admitted Patient Data Collection (APDC) and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), which collect data from all public and private hospitals in NSW, Australia. Patients who underwent a TKA or THA for OA between 1 January 2002 and 31 December 2017 were included. The main outcome measures were 90-day incidence rates of hospital readmission for: revision arthroplasty for PJI as recorded in the AOANJRR; conservative definition of PJI, defined by T84.5, the PJI diagnosis code in the APDC; and extended definition of PJI, defined by the presence of either T84.5, or combinations of diagnosis and procedure code groups derived from recursive binary partitioning in the APDC. Results. The mean 90-day revision rate for infection was 0.1% (0.1% to 0.2%) for TKA and 0.3% (0.1% to 0.5%) for THA. The mean 90-day PJI rates defined by T84.5 were 1.3% (1.1% to 1.7%) for TKA and 1.1% (0.8% to 1.3%) for THA. The mean 90-day PJI rates using the extended definition were 1.9% (1.5% to 2.2%) and 1.5% (1.3% to 1.7%) following TKA and THA, respectively. Conclusion. When reporting the revision arthroplasty for infection, the AOANJRR substantially underestimates the rate of PJI at 90 days. Using combinations of infection codes and PJI-related surgical procedure codes in linked hospital administrative databases could be an alternative way to monitor PJI rates. Cite this article: Bone Joint J 2022;104-B(9):1060–1066

Aim. As the populations of patients who have multiple prosthetic joints increase these years, the fate of a single joint periprosthetic joint infection in these patients is still unknown. Risk factors leading to a subsequent infection in another prosthetic joint are unclear. Our goal is to identify the risk factors of developing a subsequent infection in another prosthetic joint and describe the organism profile to the second prosthetic infection. Method. We performed a retrospective cohort study of all PJI cases underwent surgical intervention at our institute, a tertiary care referral center over 11 years, during January 2006 to December 2016. We identified 96 patients with periprosthetic joint infection who had another prosthetic joint in place at the time of presentation. The comorbidity, number of prosthetic joints, date and type of each arthroplasty, times of recurrent infection at each prosthetic joint with subsequent debridement or 2-stage resection arthroplasty, organisms from every infection episode, the outcome of each periprosthetic joint infection in these patients were analyzed. Results. During January 2006 to May 2017, we retrospective collected 294 PJI cases (159 hips, 135 knees) in our institute. Patients with single prosthetic joint were excluded and finally 96 patients were included. Of the 96 patients, 19 (19.79%) developed a periprosthetic joint infection in a second joint. The type of organism was the same as the first infection in 12 (63.16%) of 19 patients. The time to developing a second infection averaged 2.16 years (range, 0–9.3 years). The risk factors leading to a subsequent infection in another prosthetic joint are albumin level (< 3.5 mg/dl), long-term steroid usage (> 5mg/day, > 3 months), history of necrotizing fasciitis, history of invasive dental procedure (> Grade IV procedure), 3-stage resection arthroplasty or more, and PJI caused by vacomycin-resistent enterococcus (VRE). Conclusions. A PJI might predispose patients to subsequent PJI in another prosthesis. Patients and surgeons must be aware of the risk factors contribute to this devastating complication. Most organisms in the second PJI are identical to the first one, and we believe the bacteremia may be the pathogenesis, but need further proved. The preventive policy may be needed in the future for this population who has multiple prosthetic joints

Aims. Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative. Methods. We performed a retrospective review of patients diagnosed with hip or knee PJI between 1 January 2010 and 31 December 2019, at the Mayo Clinic in Rochester, Minnesota, USA. We included patients aged 18 years or older who had fungal, mycobacterial, or both cultures performed together with bacterial cultures. Cases with positive fungal or mycobacterial cultures were reviewed using the electronic medical record to classify the microbiological findings as representing true infection or not. Results. There were 2,067 episodes of PJI diagnosed within the study period. A total of 3,629 fungal cultures and 2,923 mycobacterial cultures were performed, with at least one of these performed in 56% of episodes (n = 1,157). Test positivity rates of fungal and mycobacterial cultures were 5% (n = 179) and 1.2% (n = 34), respectively. After a comprehensive review, there were 40 true fungal and eight true mycobacterial PJIs. BCB were 90% sensitive in diagnosing true fungal PJI and 100% sensitive in detecting rapidly growing mycobacteria (RGM). Fungal stains were performed in 27 true fungal PJI but were only positive in four episodes (14.8% sensitivity). None of the mycobacterial stains was positive. Conclusion. Routine fungal and mycobacterial stains and cultures should not be performed as they have little clinical utility in the diagnosis of PJI and are associated with significant costs. Candida species and RGM are readily recovered using BCB. More research is needed to predict rare non-Candida fungal and slowly growing mycobacterial PJI that warrant specialized cultures. Cite this article: Bone Joint J 2022;104-B(1):53–58

Aims. Achievement of accurate microbiological diagnosis prior to revision is key to reducing the high rates of persistent infection after revision knee surgery. The effect of change in the microorganism between the first- and second-stage revision of total knee arthroplasty for periprosthetic joint infection (PJI) on the success of management is not clear. Methods. A two-centre retrospective cohort study was conducted to review the outcome of patients who have undergone two-stage revision for treatment of knee arthroplasty PJI, focusing specifically on isolated micro-organisms at both the first- and second-stage procedure. Patient demographics, medical, and orthopaedic history data, including postoperative outcomes and subsequent treatment, were obtained from the electronic records and medical notes. Results. The study cohort consisted of 84 patients, of whom 59.5% (n = 50) had successful eradication of their infection at a mean follow-up of 4.7 years. For the 34 patients who had recurrence of infection, 58.8% (n = 20) had a change in isolated organism, compared to 18% (n = 9) in the infection eradication group (p < 0.001). When adjusting for confound, there was no association when the growth on the second stage was the same as the first (odd ratio (OR) 2.50, 95% confidence interval (CI) 0.49 to 12.50; p = 0.269); however, when a different organism was identified at the second stage, this was independently associated with failure of treatment (OR 8.40, 95% CI 2.91 to 24.39; p < 0.001). There were no other significant differences between the two cohorts with regard to patient demographics or type of organisms isolated. Conclusion. Change in the identified microorganism between first- and second-stage revision for PJI was associated with failure of management. Identification of this change in the microorganism prior to commencement of the second stage may help target antibiotic management and could improve the success of surgery in these patients. Cite this article: Bone Jt Open 2023;4(9):720–727

Aims. The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI. Methods. We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified. Results. Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI. Conclusion. Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: Bone Joint J 2022;104-B(3):311–320

Aims. Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective case series of 35 PJI TKA patients, with a median age of 67 years (interquartile range (IQR) 61 to 75), who underwent DAIR combined with IO vancomycin (500 mg), was performed with minimum 12 months' follow-up. A total of 26 patients with primary implants were treated for acute perioperative or acute haematogenous infections. Additionally, nine patients were treated for chronic infections with components that were considered unresectable. Primary outcome was defined by no reoperations for infection, nor clinical signs or symptoms of PJI. Results. Mean follow-up for acute infection was 16.5 months (12.1 to 24.2) and 15.8 months (12 to 24.8) for chronic infections with unresectable components. Overall non-recurrence rates for acute infection was 92.3% (24/26) but only 44.4% (4/9) for chronic infections with unresectable components. The majority of patients remained on suppressive oral antibiotics. Musculoskeletal Infection Society (MSIS) host grade was a significant indicator of failure (p < 0.001). Conclusion. The addition of IO vancomycin at the time of DAIR was shown to be safe with improved results compared to current literature using standard DAIR without IO antibiotic administration. Use of this technique in chronic infections should be applied with caution. While these results are encouraging, this technique requires longer follow-up before widespread adoption. Cite this article: Bone Joint J 2021;103-B(6 Supple A):185–190

Aim. Diagnosing periprosthetic joint infection after total joint arthroplasty is often challenging. The alpha defensin test has been recently reported as a promising diagnostic test for periprosthetic joint infection. The goal of this study was to determine the diagnostic accuracy of alpha defensin testing. Method. One hundred and eighty-three synovial alpha defensin and synovial fluid C-reactive protein (CRP) tests performed in 183 patients undergoing evaluation for periprosthetic joint infection were reviewed. Results were compared with the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infection. Results. Alpha defensin tests were performed prior to surgical treatment for infection, and 37 of these patients who had these tests were diagnosed by MSIS criteria as having infections. Among this group, the alpha defensin test had a sensitivity of 81.1% (95% confidence interval [CI], 64.8% to 92.0%) and a specificity of 95.9% (95% CI, 91.3% to 98.5%). There were 6 false-positive results, 4 of which were associated with metallosis. There were 7 false negatives, all of which were associated with either draining sinuses (n = 3) or low-virulence organisms (n = 4). A combined analysis of alpha defensin and synovial fluid CRP tests was performed in which a positive result was represented by a positive alpha defensin test and a positive synovial fluid CRP test (n = 28). Among this group, the sensitivity was calculated to be 73.0% (95% CI, 55.9% to 86.2%) and the specificity was calculated to be 99.3% (95% CI, 96.2% to 99.9%). An additional combined analysis was performed where a positive result was represented by a positive alpha defensin test or positive synovial fluid CRP test (n = 64). Among this group, the sensitivity was calculated tobe91.9%(95%CI, 78.1%to98.3%) andthe specificitywas calculated tobe79.5%(95%CI, 72.0%to85.7%). Conclusions. Alpha defensin in combination with synovial fluid CRP demonstrates very high sensitivity for diagnosing periprosthetic joint infection, but may yield false-positive results in the presence of metallosis or false-negative results in the presence of low-virulence organisms. When both alpha defensin and synovial fluid CRP tests are positive, there is a very high specificity for diagnosing periprosthetic joint infection

Purpose. Intra-articular corticosteroid injection is widely used for symptomatic relief of knee osteoarthritis. However, if pain is not improved which consequences a total knee arthroplasty (TKA), there is a potential risk of post-operative periprosthetic joint infection (PJI). The aim of this study is to investigate whether the use of preoperative intra-articular corticosteroid injection increases the risk of PJI and to investigate a time frame in which the risk of subsequent infection is significantly increased. Methods. A systematic search was performed in PubMed (Medline), Scopus, and the Cochrane Library. Inclusion criteria were original studies investigating the rate of PJI in patients receiving pre-operative intra-articular corticosteroid injection compared to controls. Results. A total of 380 unique articles were screened. Six studies met the inclusion criteria with 255,627 patients in total. Overall, no statistical significance was observed in the intra-articular infection rate in corticosteroid compared to controls groups. However, intra-articular corticosteroid injections within 3 months prior to TKA were associated with a significantly increased risk of infection (OR: 1.52, 95% CI 1.37–1.67, p < 0.01); this was not observed in the 6-month period (OR: 1.05, 95% CI 0.80–1.39, p = 0.72). Conclusions. Performing an intra-articular corticosteroid injection within 3 months prior to TKA is associated with a significantly increased risk of PJI. The current evidence supports the safe use of intra-articular corticosteroid injection more than 6 months before TKA. However, additional studies are needed to clarify the risk of PJI after TKA implantation between 3 and 6 months after the last corticoid injection

Periprosthetic joint infections (PJIs) centers are garnering the attention of different arthroplasty surgeons and practices alike. Nonetheless, their value has yet to be proven. Therefore, we evaluated weather PJI centers produce comparable outcomes to the national average of THA PJIs on a national cohort. We performed a retrospective review of patient data available on PearlDiver from 2015 – 2021. PJI THA cases were identified through ICD-10 and CPT codes. Patients treated by 6 fellowship trained arthroplasty surgeons from a PJI center were matched based on age, gender, Charlson Comorbidity Index and Elixhauser comorbidity index at a 1:1 ratio to patients from the national cohort. Compared outcomes included LOS, ED visits, number of patients readmitted, total readmissions. Sample sized did not allow the evaluation of amputation, fusion or explantation. Normality was tested through the Kolmogorov-Smirnov test. And comparisons were made with Students t-tests and Chi Square testing. A total of 33,001 THA PJIs and were identified. A total of 77 patients were identified as treated by the PJI center cohort and successfully matched. No differences were noted in regard to age, gender distribution, CCI or ECI (p=1, 1, 1 and 0.9958 respectively). Significant differences were noted in mean LOS (p<0.43), number of patients requiring readmissions (p=0.001) and total number of readmission events (p<0.001). No difference was noted on ED visits. Our study demonstrates that a PJI for THA cases may be beneficial for the national growing trend of arthroplasty volume. Future data, that allows comparison of patient's specific data will allow for further validation of PJI centers and how these can play a role in helping the national PJI growing problem

Abstract. Introduction. Periprosthetic joint infection (PJI) is a common cause of revision total knee surgery. Although debridement and implant retention (DAIR) has lower success rates in the chronic setting, it is an accepted treatment for acute PJI. There are two broad DAIR strategies: single debridement or a planned double debridement performed days apart. The purpose of this study is to evaluate the cost-effectiveness of single versus double DAIR with antibiotic beads for acute PJI in total knee arthroplasty (TKA). Methodology. A decision tree using single or double DAIR as treatment strategies for acute PJI was constructed. Quality Adjusted Life Years (QALYs) and costs associated with the two treatment arms were calculated. Treatment success rates, failure rates, and mortality rates were derived from the literature. Medical costs were derived from both the literature and Medicare data. A cost-effectiveness plane was constructed from multiple Monte Carlo trials. A sensitivity analysis identified parameters most influencing the optimal strategy decision. Results. Double DAIR with antibiotic beads was the optimal treatment strategy both in terms of the health utility state (82% of trials), and medical cost (97% of trials). Strategy tables demonstrated that as long as the success rate of double debridement is 10% or greater than the success rate of a single debridement, the two-stage protocol is cost-effective. Conclusions. This Markov analysis demonstrates that in the setting of acute PJI following TKA, a double DAIR with antibiotic beads is more cost effective than single DAIR from a societal perspective

Aim. Optimal strategies for surgical and antimicrobial management of Candida periprosthetic joint infections (PJI) are unclear. We present a retrospective case series of patients diagnosed with PJI caused by Candida spp. Method. Patients treated at our institution with Candida PJI from 01/2017 to 04/2018 were retrospectively included with isolation of Candida spp. in synovial fluid, intraoperative tissue or sonication fluid culture. PJI was defined by the proposed European Bone and Joint Infection Society (EBJIS) criteria. Treatment failure was defined as relapse or persistence of infection. Results. We included 9 patients (4 men and 5 women, mean age 75 years) involving 4 knee and 5 hip joint prosthesis. Risk factors for Candida PJI were prior PJI (n=4), diabetes mellitus (n=3), chronic kidney disease (n=3), obesity (n=3), negative-pressure wound therapy (n=3), rheumatoid arthritis (n=1) and chronic decubitus (n=1). Two patients had no risk factors for Candida PJI identified. Infection was acquired postoperatively (n=7), hematogenously (n=1) or contiguously through communicating vesico-articular sinus (n=1). The causative pathogen was C. albicans in 5, C. parapsilosis in 3, C. tropicalis in 1 patient, isolated from periprosthetic tissue samples (n=7), sonication fluid (n=3) and blood cultures (n=2); bacterial co-pathogens were isolated in 8 patients. Histopathological analysis revealed low-grade inflammation in all 6 patients, in whom it was performed. All patients were treated with oral fluconazole for 3 months, two initially received intravenous caspofungin and three received suppression with oral fluconazole for additional 9 months (total treatment 12 months). Liposomal amphotericin B (300–700 mg per 40 g bone cement) was admixed to spacer cement in 3 patients. Debridement and prosthesis retention was performed in one patient with tumor prosthesis after bone resection due to osteochondrosarcoma. In the remaining 8 patients the prosthesis was removed, with one-stage reimplantation in 1 patient and two-stage reimplantation in 3 patients (after 6 weeks, 3 months and 7 months); two patients are currently awaiting reimplantation, one died due to reason not related to PJI and another underwent knee arthrodesis. Among 5 patients with prosthesis in place, relapse occurred in one patient with prosthesis retention. Another patient experienced new PJI of the exchanged prosthesis caused by Staphylococcus aureus. Conclusions. All Candida PJI presented as chronic infection with low-grade inflammation. Treatment with prostheses retention failed, whereas in 4 patients who underwent two-stage exchange and long-term antifungal suppression, no relapse or persistence of infection was observed. All patients received oral fluconazole for ≥3 months

Aim. The clinical relevance of microbial DNA detected via next-generation sequencing (NGS) remains unknown. This multicenter study was conceived to: 1) identify species on NGS that may predict periprosthetic joint infection (PJI), then 2) build a predictive model for PJI in a developmental cohort, and 3) validate predictive utility of the model in a separate multi-institutional cohort. Method. Fifteen institutions prospectively collected samples from 194 revision TKA and 184 revision THA between 2017–2019. Synovial fluid, tissue and swabs were obtained intraoperatively and sent to MicrogenDx (Lubbock, TX) for NGS analysis. Reimplantations were excluded. Patients were classified per the 2018 ICM definition of PJI. DNA analysis of community similarities (ANCOM) was used to identify 17 bacterial species of 294 (W-value>50) for differentiating infected vs. noninfected cases. Logistic regression with LASSO selection and random-forest algorithms were then used to build a model for predicting PJI. ICM classification was the response variable (gold-standard) and species identified through ANCOM were predictors. Patients were randomly allocated 1:1 into training and validation sets. Using the training set, a model for PJI diagnosis was generated. The entire model-building procedure and validation was iterated 1000 times. Results. The model's assignment accuracy was 75.9%. There was high accuracy in true-negative and false-negative classification using this model, which has previously been a criticism of NGS. Specificity was 97.1%, PPV 75.0% and NPV 76.2%. On comparison of abundance between ICM-positive and ICM-negative patients, Staphylococcus aureus was the strongest contributor (F=0.99) to model predictive power. In contrast, Cutibacterium acnes was less predictive (F=0.309) and abundant across infected and noninfected revisions. Discussion. This is the first study to utilize predictive algorithms on a large multicenter dataset to transform analytic NGS data into a clinically relevant diagnostic model. Our collaborative findings suggest NGS may be an independent adjunct for PJI diagnosis, while also facilitating pathogen identification. Future work applying machine-learning will improve accuracy and utility of NGS

Aim. Periprosthetic joint infection (PJI) is a feared complication of total joint arthroplasty of hip (THA) or knee (TKA). Debridement, antibiotic treatment, and implant retention (DAIR) is an effective treatment of early PJI. In the Netherlands, cefazolin resistance in early PJI after primary arthroplasty is low. Little is known about causative micro-organisms and resistance patterns in PJI after revision arthroplasty. No recommendations for empirical treatment are described in the current guidelines. The aim of this study is to describe the characteristics of PJI after revision arthroplasty and to evaluate whether the used empirical treatment regimens are adequate, based on microbiology data. Method. In this retrospective study we included patients with early PJI after aseptic revision of THA or TKA, treated with DAIR between 2012 and 2020. Success rate was defined as implant retention and no persistent or recurrent infection during one year follow-up. Results. We identified 96 patients with PJI. PJI was most frequently caused by Staphylococcus spp. (n=73), Gram-negative bacilli (n=31) or Enterococcus spp. (n=13). Polymicrobial infection was diagnosed in 38 PJIs. Mismatches were present in 72 (75%) of the PJIs (95% CI: 0.66–0.84). Table 1 shows the number of mismatches per empirical treatment regimen. Figure 1 shows the responsible micro-organisms for the mismatches. Success rate of PJI treatment was significant reduced for patients with mismatching compared to matching empirical therapy: 62% vs. 95% respectively (OR: 0.09, 95% CI: 0.01–0.68, p=0.004). If vancomycin would have been the empirical treatment, mismatches would have been reduced to 31 (32%) (95% CI: 0.23–0.42). With vancomycin-ciprofloxacin combination therapy the mismatches would have been reduced to 1% (95% CI: −0.01–0.03). Conclusions. There is a high number of mismatches in empirical treatment in early PJI after revision arthroplasty, which have significant influence on the outcome. Based on our data cefazolin should not be recommended as empirical treatment for this specific group. Our data shows that review of local data is necessary to improve treatment strategies, that eventually might improve outcome. Besides changing Gram-positive coverage, a prospective study is needed to assess the benefits of broader spectrum empiric antimicrobial treatment taken into account toxicity and other side effects such as antimicrobial resistance. For any tables or figures, please contact the authors directly

Periprosthetic joint infections (PJI) are increasing in prevalence and are recognised as one of the most common modes of failure of joint replacements. Osteomyelitis arising from PJI is challenging to treat, difficult to cure and increases patient mortality 5-fold. PJI can have subtle symptoms and lie dormant or go undiagnosed for many years, suggesting persistent bacterial infection. Staphylococcus aureus is the most common pathogen causing PJI. Osteocytes are the most numerous and long-lived cell type in hard bone tissue. Our recent work has shown that S. aureus can infect and reside in human osteocytes without causing cell death, both experimentally and in bone samples from patients with PJI. Osteocytes respond to infection by the differential regulation of a large number of genes, suggesting previously unknown immune functions of this important cell type. S. aureus adapts during intracellular infection of osteocytes by adopting a quasi-dormant, small colony variant (SCV) phenotype, a property of several bacterial species known to cause PJI, which could contribute to persistent or silent infection. These findings shed new light on the aetiology of PJI and osteomyelitis in general. Further elucidation of the role of osteocytes in bone infection will hopefully lead to improved disease detection and management

Aims. The outcome of repeat septic revision after a failed one-stage exchange for periprosthetic joint infection (PJI) in total knee arthroplasty (TKA) remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat septic revision after a failed one-stage exchange, and to determine whether the Musculoskeletal Infection Society (MSIS) stage is associated with subsequent infection-related failure. Methods. We retrospectively reviewed all repeat septic revision TKAs which were undertaken after a failed one-stage exchange between 2004 and 2017. A total of 33 repeat septic revisions (29 one-stage and four two-stage) met the inclusion criteria. The mean follow-up from repeat septic revision was 68.2 months (8.0 months to 16.1 years). The proportion of patients who had a subsequent infection-related failure and all-cause revision was reported and Kaplan-Meier survival for these endpoints was determined. Patients were categorized according to the MSIS staging system, and the association with subsequent infection was analyzed. Results. At the most recent follow-up, 17 repeat septic revisions (52%) had a subsequent infection-related failure and the five-year infection-free survival was 59% (95% confidence interval (CI) 39 to 74). A total of 19 underwent a subsequent all-cause revision (58%) and the five-year all-cause revision-free survival was 47% (95% CI 28 to 64). The most common indication for the first subsequent aseptic revision was loosening. The MSIS stage of the host status (p = 0.663) and limb status (p = 1.000) were not significantly associated with subsequent infection-related failure. Conclusion. Repeat septic revision after a failed one-stage exchange TKA for PJI is associated with a high rate of subsequent infection-related failure and all-cause revision. Patients should be counselled appropriately to manage expectations. The host and limb status according to the MSIS staging system were not associated with subsequent infection-related failure. Cite this article: Bone Joint J 2022;104-B(3):386–393

Aims. As a proven and comprehensive molecular technique, metagenomic next-generation sequencing (mNGS) has shown its potential in the diagnosis of pathogens in patients with periprosthetic joint infection (PJI), using a single type of specimen. However, the optimal use of mNGS in the management of PJI has not been explored. In this study, we evaluated the diagnostic value of mNGS using three types of specimen with the aim of achieving a better choice of specimen for mNGS in these patients. Methods. In this prospective study, 177 specimens were collected from 59 revision arthroplasties, including periprosthetic tissues, synovial fluid, and prosthetic sonicate fluid. Each specimen was divided into two, one for mNGS and one for culture. The criteria of the Musculoskeletal Infection Society were used to define PJI (40 cases) and aseptic failure (19 cases). Results. The sensitivity and specificity of mNGS in the diagnosis of PJI were 95% and 94.7%, respectively, for all types of specimen. The sensitivity and specificity were 65% and 100%, respectively, for periprosthetic tissues, 87.5% and 94.7%, respectively, for synovial fluid, and 92.5% and 94.7%, respectively, for prosthetic sonicate fluid. The mNGS of prosthetic sonicate fluid outperformed that for other types of specimen in the rates of detection of pathogens (84.6%), sequencing reads (> ten-fold) and the rate of genome coverage (> five-fold). Conclusion. mNGS could serve as an accurate diagnostic tool in the detection of pathogens in patients with a PJI using three types of specimen. Due to its superior perfomance in identifying a pathogen, mNGS of prosthetic sonicate fluid provides the most value and may partly replace traditional tests such as bacteriological culture in these patients. Cite this article: Bone Joint J 2021;103-B(5):923–930

Aims. In cases of severe periprosthetic joint infection (PJI) of the knee, salvage procedures such as knee arthrodesis (KA) or above-knee amputation (AKA) must be considered. As both treatments result in limitations in quality of life (QoL), we aimed to compare outcomes and factors influencing complication rates, mortality, and mobility. Methods. Patients with PJI of the knee and subsequent KA or AKA between June 2011 and May 2021 were included. Demographic data, comorbidities, and patient history were analyzed. Functional outcomes and QoL were prospectively assessed in both groups with additional treatment-specific scores after AKA. Outcomes, complications, and mortality were evaluated. Results. A total of 98 patients were included, 52 treated with arthrodesis and 47 with AKA. The mean number of revision surgeries between primary arthroplasty and arthrodesis or AKA was 7.85 (SD 5.39). Mean follow-up was 77.7 months (SD 30.9), with a minimum follow-up of two years. Complications requiring further revision surgery occurred in 11.5% of patients after arthrodesis and in 37.0% of AKA patients. Positive intraoperative tissue cultures obtained during AKA was significantly associated with the risk of further surgical revision. Two-year mortality rate of arthrodesis was significantly lower compared to AKA (3.8% vs 28.3%), with age as an independent risk factor in the AKA group. Functional outcomes and QoL were better after arthrodesis compared to AKA. Neuropathic pain was reported by 19 patients after AKA, and only 45.7% of patients were fitted or were intended to be fitted with a prosthesis. One-year infection-free survival after arthrodesis was 88.5%, compared to 78.5% after AKA. Conclusion. Above-knee amputation in PJI results in high complication and mortality rates and poorer functional outcome compared to arthrodesis. Mortality rates after AKA depend on patient age and mobility, with most patients not able to be fitted with a prosthesis. Therefore, arthrodesis should be preferred whenever possible if salvage procedures are indicated. Cite this article: Bone Joint J 2024;106-B(7):669–679

Introduction. Management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a challenging task. Antibiotic management remains elusive due to differences in epidemiology and resistance between countries and reports. Increasing resistance of bacteria is a concern. The aim of this study was to investigate the development of antibiotic resistance of main causative bacteria in a single center. Methods. A retrospective review of all revision TKA between 2006 and 2018 in a tertiary referral center was performed. Included were cases meeting the consensus criteria for PJI with at least two positive cultures. Three chronological groups were created using a two-step cluster analysis. Results. In 129 cases of PJI there were 161 different bacteria identified by growth in culture. Of all bacteria 76.4% were gram positive, 23.6% were gram negative. Coagulase-negative Staphylococci (CNS) were diagnosed in 46.6% cultures, followed by Staphylococcus aureus in 19.8% of cultures. Overall antibiotic resistance (p=0.454) and Staphylococcus aureus resistance (p=0.788) have not increased during the study period. CNS resistance to teicoplanin (4% to 44%; p<0.001), fosfomycin (16% to 44%, p=0.016) and tetracycline (0% to 28%, p=0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and remained the most effective agent. Conclusion. The increasing resistance to several antibiotics over a little more than a decade is concerning. This study suggests that referral centres should continuously monitor obtained cultures as this has significant implications for both prophylactic treatment in primary as well as empirical antibiotic treatment in PJI. Resistance profiles may differ between centres and are subject to dynamic changes