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. 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

Aims. Synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI. Methods. Patients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken. Results. In total, 49 joints in 48 patients (mean age 68 years (SD 10; 26 females (54%), 25 knees (51%)) were included. Of these 11 joints (22%) were infected. The synovial fluid WBC count and %PMN predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 82%, 97%, 94%, 90%, and 95%, respectively. Synovial fluid IL-6 predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 73%, 95%, 90%, 80%, and 92%, respectively. A comparison of predictive performance indicated a strong agreement between tests. Conclusions. Synovial fluid IL-6 is not superior to synovial fluid WBC count and %PMN in detecting PJI. Level of Evidence: Therapeutic Level II. Cite this article: Bone Jt Open 2020;1-12:737–742

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

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. 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 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

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

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

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. Periprosthetic joint infections (PJIs) and fracture-related infections (FRIs) are associated with a significant risk of adverse events. However, there is a paucity of data on cardiac complications following revision surgery for PJI and FRI and how they impact overall mortality. Therefore, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality in this patient cohort. Methods. We prospectively included consecutive patients at high cardiovascular risk (defined as age ≥ 45 years with pre-existing coronary, peripheral, or cerebrovascular artery disease, or any patient aged ≥ 65 years, plus a postoperative hospital stay of > 24 hours) undergoing septic or aseptic major orthopaedic surgery between July 2014 and October 2016. All patients received a systematic screening to reliably detect PMI, using serial measurements of high-sensitivity cardiac troponin T. All-cause mortality was assessed at one year. Multivariable logistic regression models were applied to compare incidence of PMI and mortality between patients undergoing septic revision surgery for PJI or FRI, and patients receiving aseptic major bone and joint surgery. Results. In total, 911 consecutive patients were included. The overall perioperative myocardial injury (PMI) rate was 15.4% (n = 140). Septic revision surgery for PJI was associated with a significantly higher PMI rate (43.8% (14/32) vs 14.5% (57/393); p = 0.001) and one-year mortality rate (18.6% (6/32) vs 7.4% (29/393); p = 0.038) compared to aseptic revision or primary arthroplasty. The association with PMI persisted in multivariable analysis with an adjusted odds ratio (aOR) of 4.7 (95% confidence interval (CI) 2.1 to 10.7; p < 0.001), but was not statistically significant for one-year mortality (aOR 1.9 (95% CI 0.7 to 5.4; p = 0.240). PMI rate (15.2% (5/33) vs 14.1% (64/453)) and one-year mortality (15.2% (5/33) vs 9.1% (41/453)) after FRI revision surgery were comparable to aseptic long-bone fracture surgery. Conclusion. Patients undergoing revision surgery for PJI were at a risk of PMI and death compared to those undergoing aseptic arthroplasty surgery. Screening for PMI and treatment in specialized multidisciplinary units should be considered in major bone and joint infections. Cite this article: Bone Joint J 2022;104-B(6):696–702

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

Aims. Preoperative nasal Staphylococcus aureus screening and eradication reduces surgical site infections (SSIs) but its impact on reducing early prosthetic joint infection (PJI) remains controversial. This study aims to assess the effect of preoperative nasal S. aureus screening and eradication on the incidence of early PJI in general and S. aureus-induced early PJI. Methods. All primary total hip arthroplasties (THA) and total knee arthroplasties (TKA) performed from January 2006 to April 2018 were retrospectively reviewed for the incidence of early PJI. Demographic parameters, risk factors for PJI (American Society of Anaesthesiologists classification, body mass index, smoking status, and diabetes mellitus) and implant types were collected. A preoperative screening and eradication protocol for nasal colonization of S. aureus was introduced in October 2010. The incidence of early PJI was compared before and after the implementation of the protocol. Missing data were imputed via multiple imputation by chained equations. Inverse probability weighting was used to account for differences between patients in both groups. Weighted univariate logistic regression was used to evaluate the incidence of early PJI for both groups. Results. In total, 10,486 THAs and TKAs were performed in the research period. After exclusion, a cohort of 5,499 screened cases and 3,563 non-screened cases were available for analysis. Overall, no significant reduction in early PJI was found in the screened group (odds ratio (OR) 0.78, 95% confidence interval (CI) 0.55 to 1.11; p = 0.173). However, the incidence of S. aureus-induced PJI was significantly reduced (OR 0.58, 95% CI 0.36 to 0.92; p = 0.027) in the screened group. Conclusion. A preoperative nasal S. aureus screening and eradication protocol did not significantly reduce the overall incidence of early PJI after THA or TKA. However, a decreased incidence of S. aureus-induced early PJI was established. These findings can help to establish better consensus around the value of these screening protocols. Cite this article: Bone Joint J 2020;102-B(10):1341–1348

Aims. Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI). Methods. Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed. Results. Patients with PJI had higher CLP concentrations than those undergoing aseptic revision in blood (median PJI 2.14 mg/l (interquartile range (IQR) 1.37 to 3.56) vs AR-TJR 0.66 mg/l (IQR 0.3 to 0.83); p < 0.001) and synovial fluid samples (median PJI 20.46 mg/l (IQR 14.3 to 22.36) vs AR-TJR 0.7 mg/l (IQR 0.41 to 0.95); p < 0.001). With a cut-off value of 1.0 mg/l, blood CLP showed a sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 87.5%, 89.4%, and 92.1%, respectively. For synovial fluid with a cut-off value of 1.5 mg/l, these were 95.6%, 95%, 95.5%, and 95%, respectively. Conclusion. This small study suggests that synovial and blood CLP are useful markers in chronic PJI diagnosis with similar or higher sensitivity and specificity than routinely used markers such as CRP, ESR, IL-6, and LE. CLP was not useful to differentiate patients with PJI from those with rheumatoid arthritis. Cite this article: Bone Joint J 2021;103-B(1):46–55

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

Aims. The aim of this study was to further evaluate the accuracy of ten promising synovial biomarkers (bactericidal/permeability-increasing protein (BPI), lactoferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil elastase 2 (ELA-2), α-defensin, cathelicidin LL-37 (LL-37), human β-defensin (HBD-2), human β-defensin 3 (HBD-3), D-dimer, and procalcitonin (PCT)) for the diagnosis of periprosthetic joint infection (PJI), and to investigate whether inflammatory joint disease (IJD) activity affects their concentration in synovial fluid. Methods. We included 50 synovial fluid samples from patients with (n = 25) and without (n = 25) confirmed PJI from an institutional tissue bank collected between May 2015 and December 2016. We also included 22 synovial fluid samples aspirated from patients with active IJD presenting to Department of Rheumatology, the first Medical Centre, Chinese PLA General Hospital. Concentrations of the ten candidate biomarkers were measured in the synovial fluid samples using standard enzyme-linked immunosorbent assays (ELISA). The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves. Results. BPI, LTF, NGAL, ELA-2, and α-defensin were well-performing biomarkers for detecting PJI, with areas under the curve (AUCs) of 1.000 (95% confidence interval, 1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), and 0.998 (0.994 to 1.000), respectively. The other markers (LL-37, HBD-2, D-dimer, PCT, and HBD-3) had limited diagnostic value. For the five well-performing biomarkers, elevated concentrations were observed in patients with active IJD. The original best thresholds determined by the Youden index, which discriminated PJI cases from non-PJI cases could not discriminate PJI cases from active IJD cases, while elevated thresholds resulted in good performance. Conclusion. BPI, LTF, NGAL, ELA-2, and α-defensin demonstrated excellent performance for diagnosing PJI. However, all five markers showed elevated concentrations in patients with IJD activity. For patients with IJD, elevated thresholds should be considered to accurately diagnose PJI. Cite this article: Bone Joint J 2021;103-B(1):32–38

Aims. Removal of infected components and culture-directed antibiotics are important for the successful treatment of chronic periprosthetic joint infection (PJI). However, as many as 27% of chronic PJI patients yield negative culture results. Although culture negativity has been thought of as a contraindication to one-stage revision, data supporting this assertion are limited. The aim of our study was to report on the clinical outcomes for one-stage and two-stage exchange arthroplasty performed in patients with chronic culture-negative PJI. Methods. A total of 105 consecutive patients who underwent revision arthroplasty for chronic culture-negative PJI were retrospectively evaluated. One-stage revision arthroplasty was performed in 30 patients, while 75 patients underwent two-stage exchange, with a minimum of one year's follow-up. Reinfection, re-revision for septic and aseptic reasons, amputation, readmission, mortality, and length of stay were compared between the two treatment strategies. Results. The patient demographic characteristics did not differ significantly between the groups. At a mean follow-up of 4.2 years, the treatment failure for reinfection for one-stage and two-stage revision was five (16.7%) and 15 patients (20.0%) (p = 0.691), and for septic re-revision was four (13.3%) and 11 patients (14.7%) (p = 0.863), respectively. No significant differences were observed between one-stage and two-stage revision for 30- 60- and 90-day readmissions (10.0% vs 8.0%; p = 0.714; 16.7% vs 9.3%; p = 0.325; and 26.7% vs 10.7%; p = 0.074), one-year mortality (3.3% vs 4.0%; p > 0.999), and amputation (3.3% vs 1.3%; p = 0.496). Conclusion. In this non-randomized study, one-stage revision arthroplasty demonstrated similar outcomes including reinfection, re-revision, and readmission rates for the treatment of chronic culture-negative PJI after TKA and THA compared to two-stage revision. This suggests culture negativity may not be a contraindication to one-stage revision arthroplasty for chronic culture-negative PJI in selected patients. Cite this article: Bone Joint J 2021;103-B(3):515–521

Aims. The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods. Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm. 3. and ≥ 65% for TKA and ≥ 3,000 cells/mm. 3. and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar’s test and area under the receiver operating characteristic curve (AUC) analysis. Results. Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. Conclusion. The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119–1126

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. To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI). Methods. A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN). Results. Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/μL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/μL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing. Conclusion. The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593–599

Aims. Debridement, antibiotics, and implant retention (DAIR) is a widely accepted form of surgical treatment for patients with an early periprosthetic joint infection (PJI) after primary arthroplasty. The outcome of DAIR after revision arthroplasty, however, has not been reported. The aim of this study was to report the success rate of DAIR after revision arthroplasty with a follow-up of two years. Methods. This retrospective study, conducted at the Sint Maartenskliniek, Nijmegen, the Netherlands, included 88 patients who underwent DAIR within 90 days of revision total hip or total knee arthroplasty between 2012 and 2019. Details of the surgical procedures and PJI were collected. Univariate analysis and a subgroup analysis of the culture-positive group were performed. Kaplan-Meier survivorship curves were constructed. Results. The overall success rate of DAIR, with respect to the retention of components and the cure of infection, was 68% after two years. DAIR performed with an interval of > 30 days after the index revision procedure (odds ratio (OR) 0.24 (95% confidence interval (CI) 0.08 to 0.72); p = 0.008), a repeated DAIR within 90 days (OR 0.37 (95% CI 0.14 to 0.97); p = 0.040), and the use of an immunosuppressive agent (OR 0.13 (95% CI 0.02 to 0.67); p = 0.012) were associated with a significantly reduced success rate. In the culture-positive group, a mismatch between the antibiotic treatment and the susceptibility of the organism was associated with a significantly lower success rate (OR 0.13 (95% CI 0.03 to 0.62); p = 0.007). Conclusion. DAIR is an acceptable form of surgical treatment for patients with a suspected early PJI after revision arthroplasty of the hip or knee. DAIRs performed after a prolonged interval, multiple DAIRs, and antibiotic mismatches were significantly associated with an increased risk of failure. Optimization of the host immune response and the prevention of antibiotic mismatch are modifiable factors that may improve the outcome. The high rate of mismatches was an important finding, underlining the need for a review of the local microbiological data, which might improve the outcome. Cite this article: Bone Joint J 2022;104-B(4):464–471

Aims. To investigate the experience and emotional impact of prosthetic joint infection (PJI) on orthopaedic surgeons and identify holistic strategies to improve the management of PJI and protect surgeons’ wellbeing. Methods. In total, 18 prosthetic joint surgeons in Sweden were recruited using a purposive sampling strategy. Content analysis was performed on transcripts of individual in-person interviews conducted between December 2017 and February 2018. Results. PJI had a negative emotional impact on Swedish surgeons. Many felt guilt, stress, and a sense of failure, and several aspects of PJI management were associated with psychosocial challenges. Peer support was reported as the most important coping strategy as was collaborating with infectious disease specialists. Conclusion. Our study affirms that there is a negative emotional impact of PJI on surgeons which can be minimized by improved peer support and working in multidisciplinary teams. Based on the surgeons’ experiences we have identified desired improvements that may facilitate the management of PJI. These may also be applicable within other surgical specialties dealing with postoperative infections, but need to be evaluated for their efficacy. Cite this article: Bone Joint J 2020;102-B(6):736–743

Aims. Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure. Methods. A total of 50 patients undergoing revision hip and knee arthroplasty were enrolled into a prospective study. According to Musculoskeletal Infection Society (MSIS) criteria, 25 patients were classified as infected and 25 as not infected. In all patients, neutrophil CD64 index and percentage of polymorphonuclear neutrophils (PMN%) in synovial fluid, serum CRP, ESR, and serum CD64 index levels were measured preoperatively. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed for each biomarker. Results. Serum CD64 index showed no significant difference between the two groups (p = 0.091). Synovial fluid CD64 index and PMN% discriminated good differentiation between groups of PJI and aseptic failure with AUC of 0.946 (95% confidence interval (CI) 0.842 to 0.990) and 0.938 (95% CI 0.832 to 0.987) separately. The optimal threshold value of synovial CD64 index for the diagnosis of PJI was 0.85, with a sensitivity of 92.00%, a specificity of 96.00%, and diagnostic odds ratio (DOR) of 227.11. Conclusion. The present study demonstrates that CD64 index in synovial fluid could be a promising laboratory marker for screening PJI. The cut-off values of 0.85 for synovial CD64 index has the potential to distinguish aseptic failure from PJI. Cite this article: Bone Joint J 2020;102-B(4):463–469

Aims. Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm. Methods. We conducted an in vitro study examining the efficacy of several antiseptic solutions against clinically relevant microorganisms. We tested antiseptic irrigants against nascent (four-hour) and mature (three-day) single-species biofilm created in vitro using a drip-flow reactor model. Results. With regard to irrigant efficacy against biofilms, Povidone-iodine treatment resulted in greater reductions in nascent MRSA biofilms (logarithmic reduction (LR) = 3.12; p < 0.001) compared to other solutions. Bactisure treatment had the greatest reduction of mature Pseudomonas aeruginosa biofilms (LR = 1.94; p = 0.032) and a larger reduction than Vashe or Irrisept for mature Staphylococcus epidermidis biofilms (LR = 2.12; p = 0.025). Pooled data for all biofilms tested resulted in Bactisure and Povidone-iodine with significantly greater reductions compared to Vashe, Prontosan, and Irrisept solutions (p < 0.001). Conclusion. Treatment failure in PJI is often due to failure to clear the biofilm; antiseptics are often used as an adjunct to biofilm clearance. We tested irrigants against clinically relevant microorganisms in biofilm in vitro and showed significant differences in efficacy among the different solutions. Further clinical outcome data is necessary to determine whether these solutions can impact PJI outcome in vivo. Cite this article: Bone Joint J 2021;103-B(5):908–915

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 aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA). Patients and Methods. Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery. Results. Sensitivity and specificity of the alpha-defensin ELISA for PJI were 78.2% (95% confidence interval (CI) 66.7 to 88.5) and 96.6% (95% CI 93.0 to 99.3). Positive and negative predictive values were 89.6% (95% CI 80.6 to 97.8) and 92.2% (95% CI 87.5 to 96.1). The test remained false-negative in 22% of septic revisions, most of which were due to coagulase-negative staphylococci all occurring in either late-chronic or early-postoperative PJI. Conclusion. The routine use of synovial fluid alpha-defensin laboratory ELISA in the preoperative evaluation of symptomatic THAs and TKAs is insufficient to accurately diagnose PJI. Particularly in cases involving low-virulence organisms, such as coagulase-negative staphylococci, there remains a need for tests with a higher sensitivity. Cite this article: Bone Joint J 2019;101-B:970–977

Aims. The surgical helmet system (SHS) was developed to reduce the risk of periprosthetic joint infection (PJI), but the evidence is contradictory, with some studies suggesting an increased risk of PJI due to potential leakage through the glove-gown interface (GGI) caused by its positive pressure. We assumed that SHS and glove exchange had an impact on the leakage via GGI. Methods. There were 404 arthroplasty simulations with fluorescent gel, in which SHS was used (H+) or not (H-), and GGI was sealed (S+) or not (S-), divided into four groups: H+S+, H+S-, H-S+, and H-S-, varying by exposure duration (15 to 60 minutes) and frequency of glove exchanges (0 to 6 times). The intensity of fluorescent leakage through GGI was quantified automatically with an image analysis software. The effect of the above factors on fluorescent leakage via GGI were compared and analyzed. Results. The leakage intensity increased with exposure duration and frequency of glove exchanges in all groups. When SHS was used and GGI was not sealed (H+S-), the leakage intensity via GGI had the fastest increase, consistently higher than other groups (H+S+, H-S+ and H-S-) after 30 minutes (p < 0.05) and when there were more than four instances of glove exchange (p < 0.05). Additionally, the leakage was strongly correlated with the duration of exposure (r. s. = 0.8379; p < 0.050) and the frequency of glove exchange (r. s. = 0.8198; p < 0.050) in H+S-. The correlations with duration and frequency turned weak when SHS was not used (H-) or GGI was sealed off (S+). Conclusion. Due to personal protection, SHS is recommended in arthroplasties. Meanwhile, it is strongly recommended to seal the GGI of the inner gloves and exchange the outer gloves hourly to reduce the risk of contamination from SHS. Cite this article: Bone Jt Open 2023;4(11):859–864

Aims. In the absence of an identified organism, single-stage revision is contraindicated in prosthetic joint infection (PJI). However, no studies have examined the use of intra-articular antibiotics in combination with single-stage revision in these cases. In this study, we present the results of single-stage revision using intra-articular antibiotic infusion for treating culture-negative (CN) PJI. Methods. A retrospective analysis between 2009 and 2016 included 51 patients with CN PJI who underwent single-stage revision using intra-articular antibiotic infusion; these were compared with 192 culture-positive (CP) patients. CN patients were treated according to a protocol including intravenous vancomycin and a direct intra-articular infusion of imipenem and vancomycin alternately used in the morning and afternoon. In the CP patients, pathogen-sensitive intravenous (IV) antibiotics were administered for a mean of 16 days (12 to 21), and for resistant cases, additional intra-articular antibiotics were used. The infection healing rate, Harris Hip Score (HHS), and Hospital for Special Surgery (HSS) knee score were compared between CN and CP groups. Results. Of 51 CN patients, 46 (90.2%) required no additional medical treatment for recurrent infection at a mean of 53.2 months (24 to 72) of follow-up. Impaired kidney function occurred in two patients, and one patient had a local skin rash. No significant difference in the infection control rate was observed between CN and CP PJIs (90.2% (46/51) versus 94.3% (181/192); p = 0.297). The HHS of the CN group showed no substantial difference from that of CP cases (79 versus 81; p = 0.359). However, the CN group showed a mean HSS inferior to that of the CP group (76 versus 80; p = 0.027). Conclusion. Single-stage revision with direct intra-articular antibiotic infusion can be effective in treating CN PJI, and can achieve an infection control rate similar to that in CP patients. However, in view of systemic toxicity, local adverse reactions, and higher costs, additional strong evidence is needed to verify these treatment regimens. Cite this article: Bone Joint J 2020;102-B(3):336–344

Aims. The aim of this study was to compare the results of 16S/28S rRNA sequencing with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI). Patients and Methods. Between September 2015 and August 2016, 214 consecutive patients were enrolled. In the study population, there were 25 patients with a PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were measured, and synovial fluid specimens were collected prospectively. Synovial fluid was subjected to reverse transcription polymerase chain reaction (RT-PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture. Laboratory personnel who were blind to the clinical information performed all tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society. Results. A total of 25 patients had a confirmed PJI. In 20 cases of monomicrobial PJI, the PCR products could be perfectly matched with the 16S/28S rRNA genes specific for different species of bacteria provided by sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR sequence analysis failed to identify the concordant bacteria species. In the 189 control patients, there was one false-positive RT-PCR result. The sensitivity and specificity of the molecular diagnosis method were 100% (95% confidence interval (CI) 85.7 to 100) and 99.5% (95% CI 97.1 to 99.9), respectively, whereas the positive and negative predictive values of PCR were 96.1% (95% CI 79.6 to 99.9) and 100% (95% CI 98.1 to 100), respectively. The PCR results were significantly better than serological diagnostic methods (p = 0.004 and p = 0.010 for ESR and CRP, respectively), the synovial fluid white blood cell (WBC) count (p = 0.036), and percentage of polymorphonuclear cells (PMN%) (p = 0.014). Conclusion. Stepwise RT-PCR and sequence analysis of the 16S/28S rRNA carried out under stringent laboratory conditions achieved highly sensitive and specific results for the differentiation between aseptic and septic joints undergoing arthroplasty. Sequence analysis successfully identified bacterial strains in monomicrobial infections but failed to identify molecular targets in polymicrobial infections. Further refinement of the protocols to identify the bacteria in polymicrobial infections is needed. Cite this article: Bone Joint J 2018;100-B:1345–51

Aims. The aims of this study were to report the efficacy of revision surgery for patients with co-infective bacterial and fungal prosthetic joint infections (PJIs) presenting to a single institution, and to identify prognostic factors that would guide management. Patients and Methods. A total of 1189 patients with a PJI were managed in our bone infection service between 2006 and 2015; 22 (1.85%) with co-infective bacterial and fungal PJI were included in the study. There were nine women and 13 men, with a mean age at the time of diagnosis of 64.5 years (47 to 83). Their mean BMI was 30.9 kg/m. 2. (24 to 42). We retrospectively reviewed the outcomes of these PJIs, after eight total hip arthroplasties and 14 total knee arthroplasties. The mean clinical follow-up was 4.1 years (1.4 to 8.8). Results. The median number of risk factors for PJI was 5.5 (interquartile range (IQR) 3.25 to 7.25). All seven patients who initially underwent debridement and implant retention (DAIR) had a recurrent infection that led to a staged revision. All 22 patients underwent the first of a two-stage revision. None of the nine patients with negative tissue cultures at the second stage had a recurrent infection. The rate of recurrent infection was significantly higher in the presence of multidrug-resistant bacteria (p = 0.007), a higher C-reactive protein (CRP) at the time of presentation (p = 0.032), and a higher number of co-infective bacterial organisms (p = 0.041). The overall rate of eradication of infection after two and five years was 50% (95% confidence interval (CI) 32.9 to 75.9) and 38.9% (95% CI 22.6 to 67), respectively. Conclusion. The risk of failure to eradicate infection with the requirement of amputation associated with this diagnosis is much higher than in patients with PJI without bacterial and fungal co-infection, and this risk is heightened when the fungal organism is joined by polymicrobial and multidrug-resistant bacterial organisms. Cite this article: Bone Joint J 2019;101-B:582–588

Aims . Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI. Patients and Methods. In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay. . Results. The median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to 1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p < 0.0001). Using a cut-off value of 50 mg/L, this level showed an excellent diagnostic accuracy, with an area under the curve of 0.94. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 89%, 90%, 81% and 95% respectively. The NPV was 97% in the nine patients with a chronic PJI. . Conclusion . Synovial calprotectin may be a valuable biomarker in the diagnosis of a PJI, especially in the exclusion of an infection. With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be made. The measurement is cheap and is easy to use. . Cite this article: Bone Joint J 2017;99-B:660–5

Aims. Biopsy of the periprosthetic tissue is an important diagnostic tool for prosthetic joint infection (PJI) as it enables the detection of the responsible microorganism with its sensitivity to antibiotics. We aimed to investigate how often the bacteria identified in the tissue analysis differed between samples obtained from preoperative biopsy and intraoperative revision surgery in cases of late PJI; and whether there was a therapeutic consequence. Methods. A total of 508 patients who required revision surgery of total hip arthroplasty (THA) (n = 231) or total knee arthroplasty (TKA) (n = 277) because of component loosening underwent biopsy before revision surgery. The tissue samples collected at biopsy and during revision surgery were analyzed according to the criteria of the Musculoskeletal Infection Society (MSIS). Results. In total, 178 (113 THA, 65 TKA) were classified as infected. The biopsy procedure had a sensitivity of 93.8%, a specificity of 97.3%, a positive predictive value (PPV) of 94.9%, a negative predictive value (NPV) of 96.7%, and an accuracy of 96.1%. Of the 178 infected patients, 26 showed a difference in the detected bacteria from the biopsy and the revision surgery (14.6%). This difference required a change to antibiotic therapy in only two cases (1.1%). Conclusion. Biopsy is a useful tool to diagnose PJI, but there may be a difference in the detected bacteria between the biopsy and revision surgery. However, this did not affect the choice of antibiotic therapy in most cases, rendering the clinical relevance of this phenomenon as low. Cite this article: Bone Joint J 2020;102-B(3):329–335

Aims. The aim of this study was to determine the prevalence and characteristics of C-reactive protein (CRP)-negative prosthetic joint infection (PJI) and evaluate the influence of the type of infecting organism on the CRP level. Patients and Methods. A retrospective analysis of all PJIs affecting the hip or knee that were diagnosed in our institution between March 2013 and December 2016 was performed. A total of 215 patients were included. Their mean age was 71 years (. sd. 11) and there were 118 women (55%). The median serum CRP levels were calculated for various species of organism and for patients with acute postoperative, acute haematogenous, and chronic infections. These were compared using the Kruskal–Wallis test, adjusting for multiple comparisons with Dunn’s test. The correlation between the number of positive cultures and serum CRP levels was estimated using Spearman correlation coefficient. Results. Preoperative CRP levels were normal (< 10 mg/l) in 77 patients (35.8%) with positive cultures. Low-virulent organisms were isolated in 66 PJIs (85.7%) with normal CRP levels. When grouping organisms by species, patients with an infection caused by Propionibacterium spp., coagulase-negative staphylococci (CNS), and Enterococcus faecalis had significantly lower median serum CRP levels (5.4 mg/l, 12.2 mg/l, and 23.7 mg/l, respectively), compared with those with infections caused by Staphylococcus aureus and Streptococcus spp. (194 mg/l and 89.3 mg/l, respectively; p < 0.001). Those with a chronic PJI had statistically lower median serum CRP levels (10.6 mg/l) than those with acute postoperative and acute haematogenous infections (83.7 mg/l and 149.4 mg/l, respectively; p < 0.001). There was a significant correlation between the number of positive cultures and serum CRP levels (Spearman correlation coefficient, 0.456; p < 0.001). Conclusion. The CRP level alone is not accurate as a screening tool for PJI and may yield high false-negative rates, especially if the causative organism has low virulence. Aspiration of the joint should be used for the diagnosis of PJI in patients with a chronic painful arthroplasty, irrespective of CRP level. Cite this article: Bone Joint J 2018;100-B:1482–86

Aims. To investigate the outcomes of treatment of streptococcal periprosthetic joint infection (PJI) involving total knee and hip arthroplasties. Patients and Methods. Streptococcal PJI episodes which occurred between January 2009 and December 2015 were identified from clinical databases. Presentation and clinical outcomes for 30 streptococcal PJIs in 30 patients (12 hip and 18 knee arthroplasties) following treatment were evaluated from the medical notes and at review. The Kaplan-Meier survival method was used to estimate the probability of infection-free survival. The influence of the biofilm active antibiotic rifampin was also assessed. Results. The infection was thought to have been acquired haematogenously in 16 patients and peri-operatively in 14. The median follow-up time for successfully treated cases was 39.2 months (12 to 75), whereas failure of the treatment occurred within the first year following treatment on every occasion. The infection-free survival at three years with 12 patients at risk was 59% (95% confidence interval 39% to 75%). Failure of the treatment was observed in ten of 22 PJIs (45%) treated with a two-stage revision arthroplasty, two of six (33%) treated by debridement and prosthesis retention, and in neither of the two PJIs treated with one-stage revision arthroplasty. Streptococcal PJI treated with or without rifampin included in the antibiotic regime showed no difference in treatment outcome (p = 0.175). Conclusion. The success of treatment of streptococcal PJI in our patient cohort was poor (18 of 30 cases, 59%). New therapeutic approaches for treating streptococcal PJI are needed. Cite this article: Bone Joint J 2017;99-B:653–9

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

Aims. To investigate whether chronic kidney disease (CKD) is associated with the risk of all-cause revision or revision due to a periprosthetic joint infection (PJI) after primary hip or knee arthroplasty. Methods. This retrospective cohort study comprised 18,979 consecutive hip and knee arthroplasties from a single high-volume academic hospital. At a median of 5.6 years (interquartile range (IQR) 3.5 to 8.1), all deaths and revisions were counted. To overcome the competing risk of death, competing risk analysis using the cumulative incidence function (CIF) was applied to analyze the association between different stages of CKD and revisions. Confounding factors such as diabetes and BMI were considered using either a stratified CIF or the Fine and Gray model. Results. There were 2,111 deaths (11.1%) and 677 revisions (3.6%) during the follow-up period. PJI was the reason for revision in 162 cases (0.9%). For hip arthroplasty, 3.5% of patients with CKD stage 1 (i.e. normal kidney function, NKF), 3.8% with CKD stage 2, 4.2% with CKD stage 3, and 0% with CKD stage 4 to 5 had undergone revision within eight years. For knee arthroplasty, 4.7% with NKF, 2.7% with CKD stage 2, 2.4% with CKD stage 3, and 7% of CKD stage 4 to 5 had had undergone revision. With the exception of knee arthroplasty patients in whom normal kidney function was associated with a greater probability of all-cause revision, there were no major differences in the rates of all-cause revisions or revisions due to PJIs between different CKD stages. The results remained unchanged when diabetes and BMI were considered. Conclusion. We found no strong evidence that CKD was associated with an increased risk of all-cause or PJI-related revision. Selection bias probably explains the increased amount of all-cause revision operations in knee arthroplasty patients with normal kidney function. The effect of stage 4 to 5 CKD was difficult to evaluate because of the small number of patients. Cite this article: Bone Joint J 2021;103-B(4):689–695

Aims. It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP. Methods. We retrospectively reviewed 163 consecutive patients with periprosthetic joint infections (PJIs) who had normal ESR and CRP results pre-reimplantation in our hospital from 2014 to 2018. Of these patients, 26 had positive frozen sections at reimplantation. The minimum follow-up time was two years unless reinfection occurred within this period. Univariable and multivariable logistic regression analyses were performed to identify the association between positive frozen sections and treatment failure. Results. Treatment failure occurred in eight (30.77%) of the 26 PJI patients with positive frozen sections at reimplantation, compared with 13 (9.49%) of 137 patients with negative results. In the multivariate analysis, positive frozen section increased the risk of failure (odds ratio 4.70; 95% confidence interval (CI) 1.64 to 13.45). The mean number of months to reinfection was lower in the positive frozen section group than in the control group (p = 0.041). While there were nine (34.62%) patients with positive frozen section and 25 (18.25%) patients with negative frozen section who had prolonged antibiotic use (p = 0.042), the mean duration of antibiotic use was comparable in two groups. Synovial white blood cell count (p = 0.137) and polymorphonuclear leucocyte percentage (p = 0.454) were not associated with treatment failure in logistic regression model. Conclusion. Positive frozen section at reimplantation was independently associated with subsequent failure and earlier reinfection, despite normal ESR and CRP levels pre-reimplantation. Surgeons should be aware of the risk of treatment failure in patients with positive frozen sections and carefully consider benefits of reimplantation. Cite this article: Bone Joint J 2021;103-B(5):916–922

Aims. α-defensin is a biomarker which has been described as having a high degree of accuracy in the diagnosis of periprosthetic joint infection (PJI). Current meta-analyses are based on the α-defensin laboratory-based immunoassay rather than the quick on-table lateral flow test kit. This study is the first meta-analysis to compare the accuracy of the α-defensin laboratory-based immunoassay and the lateral flow test kit for the diagnosis of PJI. Materials and Methods. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were all clinical studies where the diagnosis of PJI was uncertain. All studies selected used the Musculoskeletal Infection Society (MSIS) or modified MSIS criteria. Two independent reviewers reviewed the studies and extracted data. A meta-analysis of results was carried out: pooled sensitivity, specificity, positive and negative likelihood ratio, heterogeneity and areas under curves are reported. Results. Ten studies (759 patients) were included. Of these, seven studies (640 patients) evaluated the laboratory-based α-defensin immunoassay and three (119 patients) the lateral flow test. The pooled sensitivity and specificity of the qualitative α-defensin laboratory immunoassay was 0.953 (95% confidence interval (CI) 0.87 to 0.984) and 0.965 (95% CI 0.943 to 0.979) respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 34.86 (95% CI 19.34 to 62.85) and 0.02 (95% CI 0.00 to 0.11). The pooled sensitivity and specificity of the lateral flow test were 0.774 (95% CI 0.637 to 0.870) and 0.913 (95% CI 0.828 to 0.958), respectively. The pooled PLR and NLR were 8.675 (95% CI 4.229 to 17.794) and 0.248 (95% CI 0.147 to 0.418), respectively. Conclusion. The pooled sensitivity and specificity of the lateral flow test were lower than those of the α-defensin laboratory-based immunoassay test. Hence, care must be taken with interpretation of the lateral flow test when relying on its results for the intra-operative diagnosis of PJI. Cite this article: Bone Joint J 2018;100-B:66–72

Aims. The purpose of this current multicentre study is to analyse the presence of alpha-defensin proteins in synovial fluid using the Synovasure lateral flow device and to determine its diagnostic reliability and accuracy compared with the prosthetic joint infection (PJI) criteria produced by the Musculoskeletal Infection Society (MSIS). Patients and Methods. A cohort of 121 patients comprising 85 total knee arthroplasties and 36 total hip arthroplasties was prospectively evaluated between May 2015 and June 2016 in three different orthopaedic centres. The tests were performed on patients with a chronically painful prosthesis undergoing a joint aspiration in a diagnostic pathway or during revision surgery. Results. Based on the MSIS criteria, 34 patients (28%) would have had a PJI, and 87 patients had no PJI. Testing with the lateral flow device had a sensitivity of 97.1% (95% confidence intervals (CI) 84.5 to 99.9) and a specificity of 96.6% (95% CI 90.3 to 99.2). The positive predictive value was 91.7% (95% CI 77.7% to 98.3), and the negative predictive value was 98.8% (95% CI 93.6 to 99.9). Receiver operator characteristics analysis demonstrated an area under the curve for the Synovasure test of 0.97 (95% CI 0.93 to 1.00). Conclusion. Our findings suggest that the Synovasure test has an excellent diagnostic performance to confirm or reject the diagnosis of a PJI. The results are promising for the care of the painful or problematic knee and hip joint arthroplasty and the test should be considered as part of the diagnostic toolbox for PJIs. Cite this article: Bone Joint J 2017;99-B:1176–82

Aims. The success rates of two-stage revision arthroplasty for infection have evolved since their early description. The implementation of internationally accepted outcome criteria led to the readjustment of such rates. However, patients who do not undergo reimplantation are usually set aside from these calculations. The aim of this study was to investigate the outcomes of two-stage revision arthroplasty when considering those who do not undergo reimplantation, and to investigate the characteristics of this subgroup. Methods. A retrospective cohort study was conducted. Patients with chronic hip or knee periprosthetic joint infection (PJI) treated with two-stage revision between January 2010 and October 2018, with a minimum follow-up of one year, were included. Variables including demography, morbidity, microbiology, and outcome were collected. The primary endpoint was the eradication of infection. Patients who did not undergo reimplantation were analyzed in order to characterize this subgroup better. Results. A total of 162 chronic PJIs were included in the study. After a mean follow-up of 57.3 months (12.1 to 115.7), 18 patients (11.1%) did not undergo reimplantation, due either to medical issues (10), the patient’s choice (4), or death (4). When only considering those who underwent reimplantation, the success rate was 80.6%. However, when those who did not undergo reimplantation were included, the success rate dropped to 71.6%. Advanced age, American Society of Anesthesiologists grade ≥ III, McPherson’s C host, and Gram-negative related PJI were independent risk factors for retention of the spacer. The mortality was higher in the non-reimplanted group. Conclusion. The real success rate of two-stage revision may not be as high as previously reported. The exclusion of patients who do not undergo reimplantation resulted in a 9% overestimation of the success rate in this series. Many comorbidity-related risk factors for retention of the spacer were identified, as well as higher death rates in this group. Efforts should be made to optimize these patients medically in order to increase reimplantation and success rates, while decreasing mortality. Cite this article: Bone Joint J 2020;102-B(12):1682–1688

Aims. The aims of this study were to increase the diagnostic accuracy of the analysis of synovial fluid in the differentiation of prosthetic joint infection (PJI) by the addition of inexpensive biomarkers such as the levels of C-reactive protein (CRP), adenosine deaminase (ADA), alpha-2-macrogloblulin (α2M) and procalcitonin. Patients and Methods. Between January 2013 and December 2015, synovial fluid and removed implants were requested from 143 revision total joint arthroplasties. A total of 55 patients met inclusion criteria of the receipt of sufficient synovial fluid, tissue samples and removed implants for analysis. The diagnosis of PJI followed the definition from a recent International Consensus Meeting to create two groups of patients; septic and aseptic. Using receiver operating characteristic curves we determined the cutoff values and diagnostic accuracy for each marker. Results. There were 23 PJIs and 32 patients with aseptic loosening. The levels of total leucocyte count, proportion of polymorphonuclear leucocytes (PMNs), CRP, ADA and α2M in the synovial fluid were all significantly higher in those with a PJI than in those with aseptic loosening. The levels of procalcitonin were comparable in the two groups. Cutoff values for the optimal performance in the diagnosis of infection were: total leucocyte count > 1463 cells/μL (sensitivity (Sens) 100%, specificity (Spec) 71.9%, positive predictive value (PPV) 71.9%, negative predictive value (NPV) 100%); proportion of PMNs > 81% (Sens 78.3%, Spec 75.0%, PPV 69.2%, NPV 82.8%); CRP > 6.7mg/L (Sens 78.3%, Spec 93.8%, PPV 90.0%, NPV 85.7%); ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%) and α2M > 958 mg/L (Sens 47.8%, Spec 96.9%, PPV 91.7%, NPV 72.1%). The addition of a raised level of CRP or ADA to the total leukocyte count increased the specificity: total leukocyte count > 1463 cells/μL and CRP > 6.7mg/L (Sens 78.3%, Spec 100%, PPV 100%, NPV 86.5%) or with ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%). . Conclusion. The total leucocyte count in the synovial fluid offers great negative predictive value in the diagnosis of PJI and the addition of more specific markers such as CRP and ADA improves the positive predictive value. Thus the addition of simple and inexpensive markers to the measurement of the leucocyte count in the synovial fluid may reduce the number of equivocal results which demand more expensive investigation. Cite this article: Bone Joint J 2017;99-B:351–7

Infection is a leading indication for revision arthroplasty. Established criteria used to diagnose prosthetic joint infection (PJI) include a range of laboratory tests. Leucocyte esterase (LE) is widely used on a colorimetric reagent strip for the diagnosis of urinary tract infections. This inexpensive test may be used for the diagnosis or exclusion of PJI. Aspirates from 30 total hip arthroplasties (THAs) and 79 knee arthroplasties (KA) were analysed for LE activity. Semi-quantitative reagent strip readings of 15, 70, 125 and 500 white blood cells (WBC) were validated against a manual synovial white cell count (WCC). A receiver operating characteristic (ROC) curve was constructed to determine the optimal cut-off point for the semi-quantitative results. Based on established criteria, six THAs and 15 KAs were classified as infected. The optimal cut-off point for the diagnosis of PJI was 97 WBC. The closest semi-quantitative reading for a positive result was 125 WBC, achieving a sensitivity of 81% and a specificity of 93%. The positive and negative predictive values of the LE test strip were 74% and 95% respectively. The LE reagent strip had a high specificity and negative predictive value. A negative result may exclude PJI and negate the need for further diagnostic tests. Cite this article: Bone Joint J 2015;97-B:1232–6

Aims. Positive cultures are not uncommon in cases of revision total knee and hip arthroplasty (TKA and THA) for presumed aseptic causes. The purpose of this study was to assess the incidence of positive intra-operative cultures in presumed aseptic revision of TKA and THA, and to determine whether the presence of intra-operative positive cultures results in inferior survival in such cases. Patients and Methods. A retrospective cohort study was assembled with 679 patients undergoing revision knee (340 cases) or hip arthroplasty (339 cases) for presumed aseptic causes. For all patients three or more separate intra-operative cultures were obtained. Patients were diagnosed with a previously unsuspected prosthetic joint infection (PJI) if two or more cultures were positive with the same organism. Records were reviewed for demographic details, pre-operative laboratory results and culture results. The primary outcome measure was infection-free implant survival at two years. Results. The incidence of unsuspected PJI was 27 out of 340 (7.9%) in TKA and 41 out of 339 (12.1%) in THA. Following revision TKA, the rate of infection-free implant survival in patients with an unsuspected PJI was 88% (95% confidence intervals (CI) 60 to 97) at two years compared with 98% (95% CI 94 to 99) in patients without PJI (p = 0.001). After THA, the rate of survival was similar in those with unsuspected PJI (92% (95% CI 73 to 98) at two years) and those without (94% (95% CI 89 to 97), p = 0.31). Conclusion. Following revision of TKA and THA for aseptic diagnoses, around 10% of cases were found to have positive cultures. In the knee, such cases had inferior infection-free survival at two years compared with those with negative cultures; there was no difference between the groups following THA. Cite this article: Bone Joint J 2017;99-B:1482–9

Aims. The diagnosis of periprosthetic joint infection (PJI) remains demanding due to limitations of all the available diagnostic tests. The synovial fluid marker, α-defensin, is a promising adjunct for the assessment of potential PJI. The purpose of this study was to investigate the qualitative assessment of α-defensin, using Synovasure to detect or exclude periprosthetic infection in total joint arthroplasty. Patients and Methods. We studied 50 patients (28 women, 22 men, mean age 65 years; 20 to 89) with a clinical indication for revision arthroplasty who met the inclusion criteria of this prospective diagnostic study. The presence of α-defensin was determined using the qualitative Synovasure test and compared with standard diagnostic methods for PJI. Based on modified Musculoskeletal Infection Society (MSIS) criteria, 13 cases were categorised as septic and 36 as aseptic revisions. One test was inconclusive. Results. The Synovasure test achieved a sensitivity of 69% and a specificity of 94%. The positive and negative likelihood ratios were 12.46 and 0.33, respectively. A good diagnostic accuracy for PJI, with an area under the curve of 0.82, was demonstrated. Adjusted p-values using the method of Hochberg showed that Synovasure is as good at diagnosing PJI as histology (p = 0.0042) and bacteriology with one positive culture (p = 0.0327). Conclusion. With its ease of use and rapid results after approximately ten minutes, Synovasure may be a useful adjunct in the diagnosis of PJI. Cite this article: Bone Joint J 2017;99-B:66–72

Aims. Fungal prosthetic joint infections (PJIs) are rare and account for about 1% of total PJIs. Our aim was to present clinical and microbiological results in treating these patients with a two-stage approach and antifungal spacers. Patients and Methods. We retrospectively reviewed our institutional database and identified 26 patients with positive fungal cultures and positive Musculoskeletal Infection Society (MSIS) criteria for PJI who were treated between 2009 and 2017. We identified 18 patients with total hip arthroplasty (THA) and eight patients with total knee arthroplasty (TKA). The surgical and antifungal treatment, clinical and demographic patient data, complications, relapses, and survival were recorded and analyzed. Results. The median follow-up was 33 months. The success rate was 38.5% (10/26). Fluconazole resistance was found in 15%. Bacterial co-infection was common in 44% of patients for THA and 66% of patients with TKA. Mortality, reoperations, and treatment failure were common complications. Conclusion. Treatment with a two-stage exchange is a possible option for treatment, although fungal infections have a high failure rate. Therapeutic factors for treatment success remain unclear. Cite this article: Bone Joint J 2019;101-B:589–595

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Total femoral arthroplasty (TFA) is a rare procedure used in cases of significant femoral bone loss, commonly from cancer, infection, and trauma. Low patient numbers have resulted in limited published work on long-term outcomes, and even less regarding TFA undertaken for non-oncological indications. The aim of this study was to evaluate the long-term clinical outcomes of all TFAs in our unit.

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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.

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The aim of this study was to determine the prevalence of depressive and anxiety disorders prior to total hip (THA) and total knee arthroplasty (TKA) and to assess their impact on the rates of any infection, revision, or reoperation.

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Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance.

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The present study aimed to investigate whether patients with inflammatory bowel disease (IBD) undergoing joint arthroplasty have a higher incidence of adverse outcomes than those without IBD.

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Nonagenarians (aged 90 to 99 years) have experienced the fastest percent decile population growth in the USA recently, with a consequent increase in the prevalence of nonagenarians living with joint arthroplasties. As such, the number of revision total hip arthroplasties (THAs) and total knee arthroplasties (TKAs) in nonagenarians is expected to increase. We aimed to determine the mortality rate, implant survivorship, and complications of nonagenarians undergoing aseptic revision THAs and revision TKAs.

Periprosthetic joint infection (PJI) is a devastating complication for patients and results in greatly increased costs of care for both healthcare providers and patients. More than 15 500 revision hip and knee procedures were recorded in England, Wales and Northern Ireland in 2013, with infection accounting for 13% of revision hip and 23% of revision knee procedures. We report our experience of using antibiotic eluting absorbable calcium sulphate beads in 15 patients (eight men and seven women with a mean age of 64.8 years; 41 to 83) as part of a treatment protocol for PJI in revision arthroplasty. . The mean follow-up was 16 months (12 to 22). We report the outcomes and complications, highlighting the risk of hypercalcaemia which occurred in three patients. We recommend that serum levels of calcium be routinely sought following the implantation of absorbable calcium sulphate beads in orthopaedic surgery. Cite this article: Bone Joint J 2015;97-B:1237–41

The aim of our study was to describe the characteristics, treatment, and outcomes of patients with periprosthetic joint infection (PJI) and normal inflammatory markers after total knee arthroplasty (TKA) and total hip arthroplasty (THA). . In total 538 TKAs and 414 THAs underwent surgical treatment for PJI and met the inclusion criteria. Pre-operative erythrocyte sedimentation rate (ESR) and C-reactive protein level (CRP) were reviewed to identify the seronegative cohort. An age- and gender-matched cohort was identified from the remaining patients for comparison. Overall, 4% of confirmed infections were seronegative (21 TKA and 17 THA). Of those who underwent pre-operative aspiration, cultures were positive in 76% of TKAs (n = 13) and 64% of THAs (n = 7). Cell count and differential were suggestive of infection in 85% of TKA (n = 11) and all THA aspirates (n = 5). The most common organism was coagulase-negative Staphylococcus. Seronegative infections were associated with a lower aspirate cell count and a lower incidence of Staphylococcus aureus infection. Two-stage revision was performed in 35 cases (95%). At a mean of five years (14 to 162 months) following revision, re-operation for infection occurred in two TKAs, and one THA. From our study we estimate around 4% of patients with PJI may present with normal ESR and CRP. When performed, pre-operative aspirate is useful in delivering a definitive diagnosis. When treated, similar outcomes can be obtained compared with patients with positive serology. Cite this article: Bone Joint J 2015;97-B:939–44

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The COVID-19 pandemic posed significant challenges to healthcare systems across the globe in 2020. There were concerns surrounding early reports of increased mortality among patients undergoing emergency or non-urgent surgery. We report the morbidity and mortality in patients who underwent arthroplasty procedures during the UK first stage of the pandemic.

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Metagenomic next-generation sequencing (mNGS) is useful in the diagnosis of infectious disease. However, while it is highly sensitive at identifying bacteria, it does not provide information on the sensitivity of the organisms to antibiotics. The purpose of this study was to determine whether the results of mNGS can be used to guide optimization of culture methods to improve the sensitivity of culture from intraoperative samples.

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The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses.

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Currently, the US Center for Medicaid and Medicare Services (CMS) has been testing bundled payments for revision total joint arthroplasty (TJA) through the Bundled Payment for Care Improvement (BPCI) programme. Under the BPCI, bundled payments for revision TJAs are defined on the basis of diagnosis-related groups (DRGs). However, these DRG-based bundled payment models may not be adequate to account appropriately for the varying case-complexity seen in revision TJAs.

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The aim of this study was to establish the diagnostic accuracy of culture of joint aspirate with and without saline injection-reaspiration.

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To evaluate the effectiveness of an institutionally developed algorithm for evaluation and diagnosis of prosthetic joint injection and to determine the impact of this protocol on overall hospital re-admissions.p

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The aim of this study was to identify the incidence of positive cultures during the second stage of a two-stage revision arthroplasty and to analyse the association between positive cultures and an infection-free outcome.

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To investigate the bone penetration of intravenous antibiotic prophylaxis with flucloxacillin and gentamicin during hip and knee arthroplasty, and their efficacy against Staphylococcus (S.) aureus and S. epidermidis.

The purpose of this study was to evaluate whether the serum level of interleukin 6 (IL-6) could be used to identify the persistence of infection after the first stage of a two-stage revision for periprosthetic joint infection.

Between 2010 and 2011, we prospectively studied 55 patients (23 men, 32 women; mean age 69.5 years; 36 to 86) with a periprosthetic joint infection. Bacteria were identified in two intra-operative tissue samples during re-implantation in 16 patients. These cases were classified as representing persistent infection.

To calculate a precise cut-off value which could be used in everyday clinical practice, a 3 x 2 contingency table was constructed and manually defined.

We found that a serum IL-6 ≥ 13 pg/mL can be regarded as indicating infection: its positive-predictive value is 90.9%. A serum IL-6 ≤ 8 pg/mL can be regarded as indicating an absence of infection: its negative predictive value is 92.1%.

The serum IL-6 level seems to be a reasonable marker for identifying persistent infection after the first stage of a revision joint arthroplasty and before attempting re-implantation.

Cite this article: Bone Joint J 2015;97-B:71–5.

Fungal peri-prosthetic infections of the knee and hip are rare but likely to result in devastating complications. In this study we evaluated the results of their management using a single-stage exchange technique. Between 2001 and 2011, 14 patients (ten hips, four knees) were treated for a peri-prosthetic fungal infection. One patient was excluded because revision surgery was not possible owing to a large acetabular defect. One patient developed a further infection two months post-operatively and was excluded from the analysis. Two patients died of unrelated causes.

After a mean of seven years (3 to 11) a total of ten patients were available for follow-up. One patient, undergoing revision replacement of the hip, had a post-operative dislocation. Another patient, undergoing revision replacement of the knee, developed a wound infection and required revision 29 months post-operatively following a peri-prosthetic femoral fracture.

The mean Harris hip score increased to 74 points (63 to 84; p < 0.02) in those undergoing revision replacement of the hip, and the mean Hospital for Special Surgery knee score increased to 75 points (70 to 80; p < 0.01) in those undergoing revision replacement of the knee.

A single-stage revision following fungal peri-prosthetic infection is feasible, with an acceptable rate of a satisfactory outcome.

Cite this article: Bone Joint J 2014;96-B:492–6.

Objectives

We wanted to investigate regional variations in the organisms reported to be causing peri-prosthetic infections and to report on prophylaxis regimens currently in use across England.

Cut-off values with highest sensitivity and specificity for the synovial fluid white cell and differential count will facilitate the accurate diagnosis of infection in total knee (TKR) and total hip replacement (THR). All patients undergoing revision TKR or THR for suspected prosthetic joint infection between 2009 and 2011 at two hospitals were identified. A total of 75 patients were included with a mean age of 70.3 years (38 to 89). Synovial fluid was aspirated pre-operatively and peri-prosthetic tissue samples were taken intra-operatively for histological and microbiological examination.

Receiver operating characteristic (ROC) plots were constructed for white cell and differential counts in aspirated fluid. The optimal cut-off for TKR and THR was 1590 white cells/µl and 65% neutrophilia. The white cell count cut-off value identified for THR was notably lower than previously quoted in the literature. A cut-off value for white cell count in synovial aspirate in suspected prosthetic joint infection of between 1100 and 1700 white cells/µl is likely to be applicable to both THR and TKR.

Cite this article: Bone Joint J 2013;95-B:554–7.

The purpose of this study was to compare the diagnostic accuracy for the detection of infection between the culture of fluid obtained by sonication (SFC) and the culture of peri-implant tissues (PITC) in patients with early and delayed implant failure, and those with unsuspected and suspected septic failure. It was hypothesised that SFC increases the diagnostic accuracy for infection in delayed, but not early, implant failure, and in unsuspected septic failure. The diagnostic accuracy for infection of all consecutive implants (hardware or prostheses) that were removed for failure was compared between SFC and PITC. This prospective study included 317 patients with a mean age of 62.7 years (9 to 97). The sensitivity for detection of infection using SFC was higher than using PITC in an overall comparison (89.9% versus 67%, respectively; p < 0.001), in unsuspected septic failure (100% versus 48.5%, respectively; p < 0.001), and in delayed implant failure (88% versus 58%, respectively; p < 0.001). PITC sensitivity dropped significantly in unsuspected compared with suspected septic failure (p = 0.007), and in delayed compared with early failure (p = 0.013). There were no differences in specificity.

Sonication is mainly recommended when there is implant failure with no clear signs of infection and in patients with delayed implant failure. In early failure, SFC is not superior to PITC for the diagnosis of infection and, therefore, is not recommended as a routine diagnostic test in these patients.

Cite this article: Bone Joint J 2013;95-B:244–9.