Aims. There is little information regarding the risk of a patient developing prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) when the patient has previously experienced PJI of a TKA or total hip arthroplasty (THA) in another joint. The goal of this study was to compare the risk of PJI of primary TKA in this patient population against matched controls. Patients and Methods. We retrospectively reviewed 95 patients (102 primary TKAs) treated between 2000 and 2014 with a history of PJI in another TKA or THA. A total of 50 patients (53%) were female. Mean age was 69 years (45 to 88) with a mean body mass index (BMI) of 36 kg/m. 2. (22 to 59). In total, 27% of patients were on chronic antibiotic suppression. Mean follow-up was six years (2 to 16). We 1:3 matched these (for age, sex, BMI, and surgical year) to 306 primary TKAs performed in 306 patients with a THA or TKA of another joint without a subsequent PJI. Competing risk with death was used for statistical analysis. Multivariate analysis was followed to evaluate risk factors for PJI in the study cohort. Results. The cumulative incidence of PJI in the study cohort (6.1%) was significantly higher than the matched cohort (2.6%) at ten years (hazard ratio (HR) 3.3; 95% confidence interval 1.18 to 8.97; p = 0.02). Host grade in the study group was not a significant risk factor for PJI. Patients on chronic suppression had a higher rate of PJI (HR 15; p = 0.002), with six of the seven patients developing PJI in the study group being on chronic suppression. The new infecting microorganism was the same as the previous in only two of seven patients. Conclusion. In this matched cohort study, patients undergoing a clean primary TKA with a history of TKA or THA PJI in another joint had a three-fold higher risk of PJI compared with matched controls with ten-year cumulative incidence of 6.1%. The risk of PJI was 15-fold higher in patients on chronic antibiotic suppression; further investigation into reasons for this and mitigation strategies are recommended. Cite this article: Bone Joint J 2019;101-B(7 Supple C):91–97

Objectives. We used the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) to investigate the risk of revision due to prosthetic joint infection (PJI) for patients undergoing primary and revision hip arthroplasty, the changes in risk over time, and the overall burden created by PJI. Methods. We analysed revision total hip arthroplasties (THAs) performed due to a diagnosis of PJI and the linked index procedures recorded in the NJR between 2003 and 2014. The cohort analysed consisted of 623 253 index primary hip arthroplasties, 63 222 index revision hip arthroplasties and 7585 revision THAs performed due to a diagnosis of PJI. The prevalence, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression. Results. We demonstrated a prevalence of revision THA due to prosthetic joint infection of 0.4/100 procedures following primary and 1.6/100 procedures following revision hip arthroplasty. The prevalence of revision due to PJI in the three months following primary hip arthroplasty has risen 2.3-fold (95% confidence interval (CI) 1.3 to 4.1) between 2005 and 2013, and 3.0-fold (95% CI 1.1 to 8.5) following revision hip arthroplasty. Over 1000 procedures are performed annually as a consequence of hip PJI, an increase of 2.6-fold between 2005 and 2013. Conclusions. Although the risk of revision due to PJI following hip arthroplasty is low, it is rising and, coupled with the established and further predicted increased incidence of both primary and revision hip arthroplasty, this represents a growing and substantial treatment burden. Cite this article: E. Lenguerrand, M. R. Whitehouse, A. D. Beswick, S. A. Jones, M. L. Porter, A. W. Blom. Revision for prosthetic joint infection following hip arthroplasty: Evidence from the National Joint Registry. Bone Joint Res 2017;6:391–398. DOI: 10.1302/2046-3758.66.BJR-2017-0003.R1

Objectives. Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. Methods. We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. Results. Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. Conclusion. IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement. Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179–188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1

Objectives. Prosthetic joint infection (PJI) is the most common cause of arthroplasty failure. However, infection is often difficult to detect by conventional bacterial cultures, for which false-negative rates are 23% to 35%. In contrast, 16S rRNA metagenomics has been shown to quantitatively detect unculturable, unsuspected, and unviable pathogens. In this study, we investigated the use of 16S rRNA metagenomics for detection of bacterial pathogens in synovial fluid (SF) from patients with hip or knee PJI. Methods. We analyzed the bacterial composition of 22 SF samples collected from 11 patients with PJIs (first- and second-stage surgery). The V3 and V4 region of bacteria was assessed by comparing the taxonomic distribution of the 16S rDNA amplicons with microbiome sequencing analysis. We also compared the results of bacterial detection from different methods including 16S metagenomics, traditional cultures, and targeted Sanger sequencing. Results. Polymicrobial infections were not only detected, but also characterized at different timepoints corresponding to first- and second-stage exchange arthroplasty. Similar taxonomic distributions were obtained by matching sequence data against SILVA, Greengenes, and The National Center for Biotechnology Information (NCBI). All bacteria isolated from the traditional culture could be further identified by 16S metagenomics and targeted Sanger sequencing. Conclusion. The data highlight 16S rRNA metagenomics as a suitable and promising method to detect and identify infecting bacteria, most of which may be uncultivable. Importantly, the method dramatically reduces turnaround time to two days rather than approximately one week for conventional cultures. Cite this article: M-F. Chen, C-H. Chang, C. Chiang-Ni, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Rapid analysis of bacterial composition in prosthetic joint infection by 16S rRNA metagenomic sequencing. Bone Joint Res 2019;8:367–377. DOI: 10.1302/2046-3758.88.BJR-2019-0003.R2

Aims. Prosthetic joint infection (PJI) and aseptic loosening in total hip arthroplasty (THA) can present with pain and osteolysis. The Musculoskeletal Infection Society (MSIS) has provided criteria for the diagnosis of PJI. The aim of our study was to analyze the utility of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) CT scan in the preoperative diagnosis of septic loosening in THA, based on the current MSIS definition of prosthetic joint infection. Patients and Methods. A total of 130 painful unilateral cemented THAs with a mean follow-up of 5.17 years (. sd. 1.12) were included in this prospective study. The mean patient age was 67.5 years (. sd. 4.85). Preoperative evaluation with inflammatory markers, aspiration, and an F18 FDG PET scan were performed. Diagnostic utility tests were also performed, based on the MSIS criteria for PJI and three samples positive on culture alone. Results. The mean erythrocyte sedimentation rate, C-reactive protein, and white cell count were 47.83 mm/hr, 25.21 mg/l, and 11.05 × 10. 9. /l, respectively. The sensitivity, specificity, accuracy, negative predictive value, and false-positive rate of FDG PET compared with MSIS criteria were 94.87%, 38.46 %, 56.38%, 94.59 %, and 60.21%, respectively. The false-positive rate of FDG PET compared with culture alone was 77.4%. Conclusion. FDG PET has a definitive role in the preoperative evaluation of suspected PJI. This the first study to evaluate its utility based on MSIS criteria and compare it with microbiology results alone. However, FDG PET has a high false-positive rate. Therefore, we suggest that F18 FDG PET is useful in confirming the absence of infection, but if positive, may not be confirmatory of PJI. Cite this article: Bone Joint J 2019;101-B:910–914

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

Aims. The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients. Methods. A group of 75 patients who underwent revision knee or hip arthroplasties were enrolled prospectively. Ten patients with primary arthroplasties were included as negative controls. Synovial fluid was collected for mNGS analysis. Optimal thresholds were determined to distinguish pathogens from background microbes. Synovial fluid, tissue, and sonicate fluid were obtained for culture. Results. A total of 49 PJI and 21 noninfection patients were finally included. Of the 39 culture-positive PJI cases, mNGS results were positive in 37 patients (94.9%), and were consistent with culture results at the genus level in 32 patients (86.5%) and at the species level in 27 patients (73.0%). Metagenomic next-generation sequencing additionally identified 15 pathogens from five culture-positive and all ten culture-negative PJI cases, and even one pathogen from one noninfection patient, while yielding no positive findings in any primary arthroplasty. However, seven pathogens identified by culture were missed by mNGS. The sensitivity of mNGS for diagnosing PJI was 95.9%, which was significantly higher than that of comprehensive culture (79.6%; p = 0.014). The specificity is similar between mNGS and comprehensive culture (95.2% and 95.2%, respectively; p = 1.0). Conclusion. Metagenomic next-generation sequencing can effectively identify pathogens from synovial fluid of PJI patients, and demonstrates high accuracy in diagnosing PJI. Cite this article: Bone Joint Res 2020;9(7):440–449

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. In 2013, we introduced a specialized, centralized, and interdisciplinary team in our institution that applied a standardized diagnostic and treatment algorithm for the management of prosthetic joint infections (PJIs). The hypothesis for this study was that the outcome of treatment would be improved using this approach. Patients and Methods. In a retrospective analysis with a standard postoperative follow-up, 95 patients with a PJI of the hip and knee who were treated with a two-stage exchange between 2013 and 2017 formed the study group. A historical cohort of 86 patients treated between 2009 and 2011 not according to the standardized protocol served as a control group. The success of treatment was defined according to the Delphi criteria in a two-year follow-up. Results. Patients in the study group had a significantly higher Charlson Comorbidity Index (3.9 vs 3.1; p = 0.009) and rate of previous revisions for infection (52.6% vs 36%; p = 0.025), and tended to be older (69.0 vs 66.2 years; p = 0.075) with a broader polymicrobial spectrum (47.3% vs 33.7%; p = 0.062). The rate of recurrent infection (3.1% vs 10.4%; p = 0.048) and the mean time interval between the two stages of the procedure (66.6 vs 80.7 days; p < 0.001) were reduced significantly in the study group compared with the control group. Conclusion. We were able to show that the outcome following the treatment of PJIs of the hip and knee is better when managed in a separate department with an interdisciplinary team using a standard algorithm

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. This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. Methods. A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. Results. According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). Conclusion. This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required. Cite this article:Bone Joint Res. 2020;9(5):202–210

Aims. The increasing infection burden after total hip arthroplasty (THA) has seen a rise in the use of two-stage exchange arthroplasty and the use of increasingly powerful antibiotics at the time of this procedure. As a result, there has been an increase in the number of failed two-stage revisions during the past decade. The aim of this study was to clarify the outcome of repeat two-stage revision THA following a failed two-stage exchange due to recurrent prosthetic joint infection (PJI). Patients and Methods. We identified 42 patients who underwent a two-stage revision THA having already undergone at least one previous two stage procedure for infection, between 2000 and 2015. There were 23 women and 19 men. Their mean age was 69.3 years (48 to 81). The outcome was analyzed at a minimum follow-up of two years. Results. A satisfactory control of infection and successful outcome was seen in 26 patients (57%). There therefore remained persistent symptoms that either required further surgery or chronic antibiotic suppression in 16 patients (38%). One-third of patients had died by the time of two years’ follow-up. Conclusion. The rate of failure and complication rate of repeat two-stage exchange THA for PJI is high and new methods of treatment including host optimization, immunomodulation, longer periods between stages, and new and more powerful forms of antimicrobial treatment should be investigated. Cite this article: Bone Joint J 2019;101-B(6 Supple B):110–115

Objectives. The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods. A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results. There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion. The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534

Objectives. The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods. A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results. There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion. The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534

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. 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. This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI. Methods. Patients scheduled to have a revision surgery for indications of chronic infection of knee and hip arthroplasties or aseptic loosening of an implant were prospectively screened before being enrolled into this study. The Musculoskeletal Infection Society (MSIS) definition of PJI was used for the classification of cases as aseptic or infected. Serum CRP, ESR, IL-6, and percentage of polymorphonuclear neutrophils (PMN%) and IL-6 in synovial fluid were analyzed. Statistical tests were performed to compare these biomarkers in the two groups, and receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Results. A total of 93 patients were enrolled. There was no difference in demographic data between both groups. Synovial fluid IL-6, with a threshold of 1,855.36 pg/ml, demonstrated a mean sensitivity of 94.59% (95% confidence interval (CI) 81.8% to 99.3%) and a mean specificity of 92.86% (95% CI 82.7 to 98.0) for detecting chronic PJI. Then 6.7 pg/ml was determined to be the optimal threshold value of serum IL-6 for the diagnosis of chronic PJI, with a mean sensitivity of 97.30% (95% CI 85.8% to 99.9%) and a mean specificity of 76.79% (95% CI 63.6% to 87.0%). The combination of synovial IL-6 and serum IL-6 led to improved accuracy of 96.77% in diagnosing chronic PJI. Conclusion. The present study identified that a combination of IL-6 in serum and synovial IL-6 has the potential for further improvement of the diagnosis of PJI. Cite this article: Bone Joint Res 2020;9(9):587–592

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. Failure of irrigation and debridement (I&D) for prosthetic joint infection (PJI) is influenced by numerous host, surgical, and pathogen-related factors. We aimed to develop and validate a practical, easy-to-use tool based on machine learning that may accurately predict outcome following I&D surgery taking into account the influence of numerous factors. Methods. This was an international, multicentre retrospective study of 1,174 revision total hip (THA) and knee arthroplasties (TKA) undergoing I&D for PJI between January 2005 and December 2017. PJI was defined using the Musculoskeletal Infection Society (MSIS) criteria. A total of 52 variables including demographics, comorbidities, and clinical and laboratory findings were evaluated using random forest machine learning analysis. The algorithm was then verified through cross-validation. Results. Of the 1,174 patients that were included in the study, 405 patients (34.5%) failed treatment. Using random forest analysis, an algorithm that provides the probability for failure for each specific patient was created. By order of importance, the ten most important variables associated with failure of I&D were serum CRP levels, positive blood cultures, indication for index arthroplasty other than osteoarthritis, not exchanging the modular components, use of immunosuppressive medication, late acute (haematogenous) infections, methicillin-resistant Staphylococcus aureus infection, overlying skin infection, polymicrobial infection, and older age. The algorithm had good discriminatory capability (area under the curve = 0.74). Cross-validation showed similar probabilities comparing predicted and observed failures indicating high accuracy of the model. Conclusion. This is the first study in the orthopaedic literature to use machine learning as a tool for predicting outcomes following I&D surgery. The developed algorithm provides the medical profession with a tool that can be employed in clinical decision-making and improve patient care. Future studies should aid in further validating this tool on additional cohorts. Cite this article: Bone Joint J 2020;102-B(7 Supple B):11–19

Aims. Preoperative diagnosis is important for revision surgery after prosthetic joint infection (PJI). The purpose of our study was to determine whether reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which is used to detect bacterial ribosomal RNA (rRNA) preoperatively, can reveal PJI in low volumes of aspirated fluid. Methods. We acquired joint fluid samples (JFSs) by preoperative aspiration from patients who were suspected of having a PJI and failed arthroplasty; patients with preoperative JFS volumes less than 5 ml were enrolled. RNA-based polymerase chain reaction (PCR) and bacterial culture were performed, and diagnostic efficiency was compared between the two methods.According to established Musculoskeletal Infection Society (MSIS) criteria, 21 of the 33 included patients were diagnosed with PJI. Results. RNA-based PCR exhibited 57.1% sensitivity, 91.7% specificity, 69.7% accuracy, 92.3% positive predictive value, and 55.0% negative predictive value. The corresponding values for culture were 28.6%, 83.3%, 48.5%, 75.0%, and 40.0%, respectively. A significantly higher sensitivity was thus obtained with the PCR method versus the culture method. Conclusion. In situations in which only a small JFS volume can be acquired, RNA-based PCR analysis increases the utility of preoperative puncture for patients who require revision surgery due to suspected PJI. Cite this article:Bone Joint Res. 2020;9(5):219–224

Aims. The aim of this study was to establish the diagnostic accuracy of culture of joint aspirate with and without saline injection-reaspiration. Patients and Methods. This is a retrospective analysis of 580 hip and knee aspirations in patients who were deemed to have a moderate to high risk of infection, and who subsequently proceeded to revision arthroplasty over a period of 12 years. It was carried out at a large quaternary referral centre where preoperative aspiration is routine. Results. Fluid was aspirated primarily in 313 (54%) cases and after saline injection-reaspiration of a ‘dry tap’ in 267 (46%) cases. Overall sensitivity and specificity of the diagnostic aspirate were 84% (78% to 89%) and 85% (81% to 88%), respectively. Sensitivity and specificity of saline injection-reaspiration after ‘dry tap’ were 87% (79% to 92%) and 79% (72% to 84%) compared with 81% (71% to 88%) and 90% (85% to 93%) for direct aspiration. Conclusion. Preoperative joint aspiration and culture is a sensitive and specific test for the confirmation of diagnosis in patients at a moderate to high risk of prosthetic joint infection. Culture of saline injection-reaspiration also provides accurate diagnostic information in the event of a ‘dry tap’. Both methods allow susceptibility testing of relevant organisms and are therefore able to guide perioperative antibiotic therapy. Cite this article: Bone Joint J 2018;100-B:749–54

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

Aim. Prosthetic joint replacement is more commonly done in the elderly group of patients due to an increase pathology related to joint degeneration that comes with age. In this age group is also more frequent having underling condition that may predispose to a prosthetic joint infection. Also, the pharmacological intervention in those patients may play an important role as a risk factor for infection after joint replacement surgery. The use of oral anticoagulants seems to be particularly increased in elderly patients but there aren't enough data published to support an association between prosthetic joint infection and the use of oral anticoagulants. Identifying risk factors in elderly patients age >75 years old with a special focus on the oral anticoagulation therapy is the aim of the study. Methods. In a retrospective study from 2011 till 2018 all the patients >75 years old with knee and hip replacement surgery have been review looking for acute prosthetic infection and risk factors that may be predispose to it. Patients with previous surgery or any other mechanical complication that needed intervention on the same area have been excluded. Results. A total of 1220 patients have been included (801 knee replacement surgery and 419 hip replacement surgery). The mean age was 79.5 ± 3.44 years and most of the patients were women (72,6%). The infection rate was 2,5%. Several factors have been identified to be associated with acute infection. (Table.1.). The patients receiving oral anticoagulants had an increased risk of infection (OR 3.63 (1.60–7.74), p=0.002). Conclusions. Even all the risk factors associated with risk infection have been described previously, the relevant aspect is the increased risk of prosthetic joint infection in patients receiving oral anticoagulants

Aim. Culture negative (CN) prosthetic joint infections (PJI) account for approximately 10% of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJI within a large prospective cohort study, and to compare their characteristics and outcomes with culture positive cases. Methods. The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, binational, multicentre observational cohort study conducted at 27 hospitals between July 2014 and December 2017. We compared baseline characteristics and outcomes of all patients with culture negative (CN) prosthetic joint infection (PJI) from the PIANO cohort with culture positive (CP) cases. “Treatment success” was defined as absence of clinical or microbiological signs of infection, no need for ongoing antibiotics, and no need for revision or resection arthroplasty since the end of the initial treatment. We also describe PJI diagnostic criteria in the CN cohort and apply internationally recognised PJI diagnostic guidelines. Results. Of the 650 patients eligible for inclusion, 55 (8.5%) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female [32 (58.2%) vs 245 (41.2%); p=0.02], involve the shoulder joint [5 (9.1%) vs. 16 (2.7%); p=0.03] and have a lower mean C-reactive protein (142 mg/L vs. 187 mg/L; p=0.02). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (aOR 3.78; 95%CI 1.65 – 8.67). Of the 55 CN cases meeting Infectious Diseases Society of America (IDSA) diagnostic criteria, 45 (82%) met European Bone and Joint Infection Society (EBJIS) criteria (probable or definite) and 39 (71%) met the 2013 Musculoskeletal Infection Society (MSIS) criteria. Conclusions. Culture negativity is an independent predictor of treatment success in PJI. It is unclear whether this is because some of them are not actually infections, or for other reasons such as lower bacterial load or earlier effective antibiotic treatment. Diagnostic criteria for PJI vary substantially in their sensitivity, with MSIS criteria being the least sensitive. Acknowledgements. This work is being presented on behalf of the broader PIANO investigators and the Australasian Society for Infectious Diseases Clinical Research Network. The PIANO study received seed funding from Heraeus Medical and the John Hunter Hospital Charitable Trust Fund

Aims. Two-stage exchange arthroplasty is the most common definitive treatment for prosthetic joint infection (PJI) in the USA. Complications that occur during treatment are often not considered. The purpose of this study was to analyze complications in patients undergoing two-stage exchange for infected total knee arthroplasty (TKA) and determine when they occur. Methods. We analyzed all patients that underwent two-stage exchange arthroplasty for treatment of PJI of the knee from January 2010 to December 2018 at a single institution. We categorized complications as medical versus surgical. The intervals for complications were divided into: interstage; early post-reimplantation (three months); and late post-reimplantation (three months to minimum one year). Minimum follow-up was one year. In total, 134 patients underwent a first stage of a two-stage exchange. There were 69 males and 65 females with an mean age at first stage surgery of 67 years (37 to 89). Success was based on the new Musculoskeletal Infection Society (MSIS) definition of success reporting. Results. Overall, 70 (52%) patients experienced a complication during the planned two-stage treatment, 36 patients (27%) experienced a medical complication and 47 (41%) patients experienced a surgical complication. There was an 18% mortality rate (24/134) at a mean of 3.7 years (0.09 to 8.3). During the inter-stage period, 28% (37/134) of patients experienced a total of 50 complications at a median of 47 days (interquartile range (IQR) 18 to 139). Of these 50 complications, 22 were medical and 28 required surgery. During this inter-stage period, four patients died (3%) and an additional five patients (4%) failed to progress to the second stage. While 93% of patients (125/134) were reimplanted, only 56% (77/134) of the patients were successfully treated without antibiotic suppression (36%, 28/77) or with antibiotic suppression (19%, 15/77) at one year. Conclusion. Reported rates of success of two stage exchanges for PJI have not traditionally considered complications in the definition of success. In our series, significant numbers of patients experienced complications, more often after reimplantation, highlighting the morbidity of this method of treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):145–150

Prosthetic joint infections (PJI) are devastating complications. Our knowledge on hip fractureassociated hemiarthroplasty PJI (HHA-PJI) is limited compared to elective arthroplasty. The goal of this study was to describe the epidemiology, risk factors, management, and outcomes for HHA-PJI. A population-based (465,000) multicentre retrospective analysis of HHAs between 2006-2018 was conducted. PJI was defined by international consensus and treatment success as no return to theatre and survival to 90 days after the initial surgical management of the infection. Univariate, survival and competing risk regression analyses were performed. 1852 HHAs were identified (74% female; age:84±7yrs;90-day-mortality:16.7%). Forty-three (2.3%) patients developed PJI [77±10yrs; 56% female; 90-day-mortality: 20.9%, Hazard-Ratio 1.6 95%CI 1.1-2.3,p=0.023]. The incidence of HHA-PJI was 0.77/100,000/year and 193/100,000/year for HHA. The median time to PJI was 26 (IQR 20-97) days with 53% polymicrobial growth and 41% multi-drug resistant organisms (MDRO). Competing risk regression identified younger age [Sub-Hazard-Ratio(SHR) 0.86, 95%CI 0.8-0.92,p<0.001], chronic kidney disease (SHR 3.41 95%CI 1.36-8.56, p=0.01), body mass index>35 (SHR 6.81, 95%CI 2.25-20.65, p<0.001), urinary tract infection (SHR 1.89, 95%CI 1.02-3.5, p=0.04) and dementia (SHR 9.4, 95%CI 2.89-30.58,p<0.001) as significant risk factors for developing HHA-PJI. When infection treatment was successful (n=15, 38%), median survival was 1632 days (IQR 829-2084), as opposed to 215 days (IQR 20-1245) in those who failed, with a 90-day mortality of 30%(n=12). There was no significant difference in success among debridement, excision arthroplasty or revision arthroplasty. HHA PJI is uncommon but highly lethal. All currently identified predictors are non-modifiable. Due to the common polymicrobial and MDRO infections our standard antibiotic prophylaxis may not be adequate HHA-PJI is a different disease compared to elective PJI with distinct epidemiology, pathogens, risk factors and outcomes, which require targeted research specific to this unique population

Aims. This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) . Methods. A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy. Results. The median calprotectin level was 776 μg/ml (interquartile range (IQR) 536.5 to 1132) in the PJI group and 54.5 μg/ml (IQR, 38.75 to 78.25) in the aseptic failure (AF) group (p < 0.05). Using a threshold of 173 ug/ml, the sensitivity was 95.2%, with a 97.6% specificity, and the AUC was 0.993. The sensitivity of calprotectin of the antibiotic-treated PJI group was 100% versus 90.9% of the non-antibiotic-treated PJI group. Although 47.6% (ten cases) of the patients in the PJI group received antibiotics before aspiration, the diagnostic efficacy of calprotectin was not affected. The sensitivity and specificity of ESR, CRP, SF-WBCs, and SF-PMNs ranged from 76.2% to 90.5% and 64.3% to 85.7%, respectively. Conclusion. Calprotectin in synovial fluid has great diagnostic efficacy for PJI diagnosisand outperformed ESR, CRP, SF-WBCs, and SF-PMNs. Cite this article: Bone Joint Res 2020;9(8):450–456

Introduction. A proportion of patients with hip and knee prosthetic joint infection (PJI) undergo multiple revisions with the aim of eradicating infection and improving quality of life. The aim of this study was to describe the microbiology cultured from multiply revised hip and knee replacement procedures to guide antimicrobial therapy at the time of surgery. Patients and Methods. Consecutive patients were retrospectively identified from databases at two specialist orthopaedic centres in the United Kingdom between 2011 and 2019. Patient were included who had undergone repeat revision total knee replacement (TKR) or total hip replacement (THR) for infection, following an initial failed revision for infection. Results. 106 patients were identified, of which 74 underwent revision TKR and 32 underwent revision THR. Mean age at first revision was 67 years (SD 10). Charlson Comorbidity Index was <2 for 31 patients, 3–4 for 57 patients, and >5 for 18 patients. All patients underwent >2 revisions, 73 patients received 3, 47 patients received 4, 31 patients received 5, and 21 patients received >6. After six revisions, 90% of patients cultured different organisms than the initial revision, and 53% of organisms were multi-drug resistant species. The most frequent organisms at each revision were coagulase negative Staphylococcus (36%) and Staphylococcus aureus (19%). Fungus was cultured from 3% of revisions and 21% of infections were polymicrobial. Conclusion. Patients undergoing multiple revisions for PJI are highly likely to experience a change in organisms and sensitivities with each subsequent revision. It is important to administer empirical antibiotics at each subsequent revision, appreciating known drug resistance from previous cultures. Our results do not support routine use of empirical antifungals

Prosthetic joint infections (PJI) are one of the most devastating complications of joint replacement surgery. They are associated with significant patient morbidity and carry a significant economic cost to treat. The management of PJI varies from antibiotic suppression, debridement, antibiotics, and implant retention (DAIR) procedures through to single/multiple stage revision procedures. Concerns have been raised recently in relation to the rising number of revision arthroplasty procedures that are being undertaken in relation to infection. This database aims to collect data on all PJIs that have been managed in the Australian Capital Territory (ACT) region. This will allow us to investigate the microbial trends, outcomes of surgical intervention and patient outcomes within our local population. This database will incorporate diagnostic, demographic, microbiological and treatment information in relation to local PJI cases. The data will be collated from the local infectious diseases database, hospital medical records, and where available the Australian Orthopaedic Association National Joint Replacement Registry Data. The first 100 cases of PJI were assessed. 76% were defined as being acute. 56% of the patients received antibiotics prior to their diagnosis however only 3% were culture negative. 89% were monomicrobial and 11% polymicrobial. The intended management strategy was a DAIR in 38% of patients and a 2-stage revision in 12% of cases. The intended management strategy was successful in 46% of the patients. The ACT is uniquely placed to analyze and create a local PJI database. This will allow us to guide further treatment and local guidelines in terms of management of these complex patients

Aim. Prosthetic joint infection (PJI) is a devastating complication of joint replacement, having an impact on morbimortality but also on national health systems and their budgets. The current situation of PJI-related hospitalizations in Spain and their changes over time are unknown. Therefore, we aimed to analyze the hospitalization burden of PJI, including costs and trends in recent decades. Methods. Retrospective observational study including data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. During the period 2000–2015, hospitalizations due to PJI (ICD-9-CM 996.66) as main diagnosis were included. Epidemiological trends were evaluated during four periods: P1, 2000–2003; P2, 2004–2007; P3, 2008–2011; P4, 2012–2015. Annual hospitalization rates per 100,000 inhabitants and trends were also calculated. Results. Among 5,721,6725 hospitalizations, 49,835 were PJI related, which represented 8.71/10,000 admissions. We observed a significant increase in the number of PJI-related hospitalizations per 10,000 admissions during the study period: 6.43 P1, 8.53 P2, 9.60 P3, 10.05 P4 (p<0.001). The annual hospitalization rate was 6.9/100,000 inhabitants (95%CI 6.9–7), which also increased over time (p<0.001). The median age was 72 years (IQR 65–78) and 58.12% were women. Hospitalization rates were higher in women (7.95 vs 5.90; p<0.001) and also increased with patients’ age (p<0.001). Whereas the median length of stay was 7 days (IQR 7–8) in the global cohort, it was 18 days (IQR 10–31) in those with PJI-related hospitalization; however, the median length of stay in PJI-related hospitalizations decreased during the study period (P1 20 days, P4 16 days, p<0.001). The total cost for the healthcare system was 366 million euros and the median cost per patient was 6937 euros (IQR 3584–10505), which significantly increased from 4804 euros in P1 to 8534 in P4 (p<0.001). The majority of patients (90.32%) were discharged home and the case-fatality rate was 2.70%, without significant differences during the study (p=0.384). Conclusions. In Spain, PJI-related hospitalizations have increased in recent decades, with higher costs despite the decrease in length of stay. PJI is a first magnitude healthcare problem, which should be prioritized in health systems and budgets

Introduction. Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. The purpose of this study is to establish a clinically representative GN-PJI model that can reliably recapitulate biofilm formation on titanium implant surface in vivo. We hypothesized that biofilm formation on an implant surface will affect its ability to osseointegrate. Methods. The model was developed using 3D-printed titanium hip implants, to replace the femoral head of male Sprague-Dawley rats. GN-PJI was induced using two bioluminescent Pseudomonas aeruginosa strains: a reference strain (PA14-lux) and a mutant biofilm-defective strain (ΔflgK-lux). Infection was monitored in real-time using the in vivo imaging system (IVIS) and Magnetic Resonance Imaging (MRI). Bacterial loads on implant surface and in periprosthetic tissues were quantified utilizing viable-colony-count. Field-emission scanning-electron-microscopy of the explanted implants was used to visualize the biofilm formation at the bone-implant-interface. The implant stability, as an outcome, was directly assessed by quantifying the osseointegration in vitro using microCT scan, and indirectly assessed by identifying the gait pattern changes using DigiGait. TM. system in vivo. Results. Localized infection was established within the hip joint and was followed by IVIS in real-time. There was a quantitative and qualitative difference in the bacterial load and biofilm formation between PA14-lux and ΔflgK-lux. This difference in the ability to persist in the model between the two strains was reflected in the gait pattern and implant osseointegration. Conclusions. We developed a novel uncemented hip hemiarthroplasty, GN-PJI rat model. To date, the proposed in vivo biofilm-based model is the most clinically representative for GN-PJI since animals can bear weight on the implant and poor osseointegration correlates with biofilm formation. In addition, localized PJI was detected by various modalities. Clinical Relevance. The proposed in vivo GN-PJI model will allow for more reliable testing of novel biofilm-targeting therapeutics

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

Introduction. The burden of prosthetic joint infection (PJI) in total knee arthroplasty (TKA) has been rising in line with the number of primary operations performed. Current estimates suggest an infection rate of 1–2.4%. Two-stage revision has traditionally been considered the gold standard of treatment; however, some studies suggest comparable results can be achieved with single-stage procedures. The potential advantages include less time in hospital, a single anaesthetic, reduced costs, and greater patient satisfaction. Methods. We reviewed data for 72 patients (47 males, 25 females), with a mean age of 71 years (range, 49 to 94), who underwent single-stage revision TKA for confirmed PJI between 2006 and 2016. A standardized debridement protocol was performed with immediate single-stage exchange. All cases were discussed preoperatively at multidisciplinary team (MDT) meetings, which included input from a senior musculoskeletal microbiologist. Patients were not excluded for previous revisions, culture-negative PJI, or the presence of a sinus. Results. The average length of follow-up was 8 years (range, 2 to 13). In total, 65 patients (90.3%) were infection free at most recent follow-up, with seven reinfections (9.7%). Three of these patients with recurrent infections underwent arthrodesis, two underwent re-revision, and two received long-term antibiotics following debridement and implant retention (DAIR). No amputations were undertaken. Conclusions. Single-stage revision for the infected TKA, according to a strict debridement protocol with MDT input, demonstrates reinfection rates comparable with two-stage revision procedures. This is the largest single-surgeon series to date, with extensive follow-up, and supports a growing evidence base for one-stage exchange

Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. To date, there are no animal models that can fully recapitulate how a biofilm is challenged in vivo in the setting of GN-PJI. The purpose of this study is to establish a clinically representative GN-PJI in vivo model that can reliably depict biofilm formation on titanium implant surface. We hypothesized that the biofilm formation on the implant surface would affect the ability of the implant to be osseointegrated. The model was developed using a 3D-printed, medical-grade titanium (Ti-6Al-4V), monoblock, cementless hemiarthroplasty hip implant. This implant was used to replace the femoral head of a Sprague-Dawley rat using a posterior surgical approach. To induce PJI, two bioluminescent Pseudomonas aeruginosa (PA) strains were utilized: a reference strain (PA14-lux) and a mutant strain that is defective in biofilm formation (DflgK-lux). PJI development and biofilm formation was quantitatively assessed in vivo using the in vivo imaging system (IVIS), and in vitro using the viable colony count of the bacterial load on implant surface. Magnetic Resonance Imaging (MRI) was acquired to assess the involvement of periprosthetic tissue in vivo, and the field emission scanning electron microscopy (FE-SEM) of the explanted implants was used to visualize the biofilm formation at the bone-implant interface. The implant stability, as an outcome, was directly assessed by quantifying the osseointegration using microCT scans of the extracted femurs with retained implants in vitro, and indirectly assessed by identifying the gait pattern changes using DigiGaitTM system in vivo. A localized prosthetic infection was reliably established within the hip joint and was followed by IVIS in real-time. There was a quantitative and qualitative difference in the bacterial load and biofilm formation between PA14 and DflgK. This difference in the ability to persist in the model between the two strains was reflected on the gait pattern and implant osseointegration. We developed a novel uncemented hip hemiarthroplasty GN-PJI rat model. This model is clinically representative since animals can bear weight on the implant. PJI was detected by various modalities. In addition, biofilm formation correlated with implant function and stability. In conclusion, the proposed in vivo GN-PJI model will allow for more reliable testing of novel biofilm-targeting therapetics

Aim. Prosthetic joint infection (PJI) is a serious complication following total hip arthroplasty (THA) entailing increased mortality, decreased quality of life, and high healthcare costs. In 2009 a nationwide, multidisciplinary infection control program was launched in Sweden, PRISS, which aimed to reduce the PJI burden by 50%. The primary aim was to investigate whether the PRISS project reduced PJI incidence after primary THA; the secondary aim was to evaluate other possible benefits of PRISS, such as shorter time to diagnosis. Method. We obtained data on patients undergoing primary THA in Sweden (n = 45,723 patients, 49,946 THAs), 2012–2014. Using personal identity numbers, this cohort was matched with the Swedish Prescribed Drug Registry. Medical records of patients with ≥4 weeks antibiotic consumption were reviewed to verify PJI diagnosis (n = 2240, 2569 THAs). Results. The cumulative incidence of PJI following the PRISS project was 1.2% [95% CI 1.1–1.3] as compared to 0.9% [95% CI 0.8–1.0] before. Cox regression models for the PJI incidence post PRISS indicates there were no statistical significance difference versus pre PRISS (HR 1.1 [95% CI 0.9–1.3]. There were similar time to PJI diagnosis after the PRISS project 24 vs 23 days (p=0.5). Conclusions. Despite the comprehensive nationwide PRISS project, Swedish PJI incidence was higher after the project and time to diagnosis remained unchanged. Factors contributing to PJI, such as increasing obesity, higher ASA class, and more fractures as indications, explain the PJI increase among primary THA patients

Aim. To provide proof of concept in an in vivo animal model for the prevention of prosthetic joint infection prevention using electric fields along with conventional antibiotic prophylaxis. Corresponding Author: Marti Bernaus. Method. First, we standardized the animal model to simulate implant contamination during the surgical procedure. We then implanted cobalt-chrome prostheses adapted to both knees of two New Zealand White rabbits, under standard aseptic measures and antibiotic prophylaxis with cefazolin. Prior to implantation, we immersed the prostheses in a 0.3 McFarland inoculum of S. aureus (ATCC 25923) for 30 seconds. In the first animal (control), the joint was directly closed after washing with saline. In the second animal (case), both prostheses were treated with electric current pulses for 30 seconds, washed with saline, and the joint was closed. After 72 hours, both animals were reoperated for the collection of periprosthetic tissue and bone samples, and prosthesis removal. In all samples, we performed quantitative cultures prior to vortexing and sonication, as well as prolonged cultures of the sonication broth. We confirmed the absence of contamination by identification with MALDI-TOF (VITEK-MS) and automated antibiotic susceptibility testing of the isolated colonies (VITEK-2). Results. In the “control” animal, we isolated S. aureus in all studied samples. The bacterial count expressed as log10 (cfu/cm2) in the prostheses of the right and left legs was 9.38 and 8.86, respectively. The bacterial count expressed as log10 (cfu/mL) in bone and periprosthetic tissue biopsies was 2.70 and 2.72 in the right leg and 3.24 and 3.87 in the left leg, respectively. In the “case” animal, where an electric field was applied to the implant after placement in addition to cefazolin prophylaxis, all samples (prosthesis, bone, and periprosthetic tissue) were negative, and no isolation of the inoculated strain of S. aureus was obtained after incubation of the sonication broth for 14 days. Conclusions. This in vivo model suggests the potential effectiveness of applying an electric field to a prosthetic implant in combination with cefazolin for the prevention of PJI development, after exposure of the implant to an inoculum of S. aureus (ATCC 25923). Our findings need to be confirmed using a larger sample size

The management of prosthetic joint infection (PJI) has been widely performed for total hip arthroplasties (THA), but none has compared it with hip resurfacing arthroplasty (RSA). We also carried out a retrospective case-control study comparing the surgical treatment of PJI by surgical debridement and implant retention between RSA and THA in order to clarify whether there was a difference in terms of (1) successful healing of PJI (2) functional scores after recovery (3) risk factors for recurrence of PJI. Our hypothesis was that simple debridement with prosthesis retention regardless of the timeframe allowed to obtain a higher success rate for RSA compared to THA. From 2010 to 2018, a single-center case-control study based on 3056 RSA found 13 PJI were age-matched (based on the 139 THA PJI treated) with 15 THA PJI (mean age of 53 years old (47–58) for THA and 59 (45–66) for RSA (p=0.34)). We compared their survival (absence of infectious recurrence) and the means differences between the 2 groups (demographical, clinical and biological data). There was no difference between the 2 groups concerning: age (p=0.3), BMI (p=0.4), initial diagnosis (p=0.4), operating time for primary surgery (p=0.3), the presence of a postoperative hematoma (p=0.4), the type of bacteria (p=0.5), the total duration of antibiotic therapy (p=0.9) and the type of antibiotic therapy (p=0.6). Early postoperative infections (less than 6 weeks) occurred in 7/13 RSA cases (54%) compared to 11/15 THA cases (73%). At the mean follow-up of 5 years (2–7), the success rate without recurrence was significantly higher in the RSA group 100% versus 66.7% (10/15) for the THA group (p=0.044). At the last follow-up, the Oxford Hip Score was higher in the RSA versus THA group's (14 versus 22 p=0.004). Simple surgical debridement an RSA without changing implants after PJI can be done regardless of the time to onset of infection. This is secondary to the absence of metaphyseal bone invasion and the low content of joint fluid

Background. Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods. In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with DAIR or one-stage revision surgery between January 1. st. , 2015 and November 3. rd. , 2020, were included. Patients were treated according to a predefined protocol for PJI. Antimicrobial treatment strategies differed between centers, which was accepted and used as pseudorandomization. Depending on the hospital patients were admitted to, they were treated with either a long-term rifampicin strategy (consisting of 12 weeks rifampicin combination therapy) ore one of several short-term rifampicin strategies, consisting of only five days of rifampicin combination treatment, started immediately postoperative, followed by clindamycin, flucloxacillin or vancomycin monotherapy. Patients were stratified in different groups, depending on the used antimicrobial strategy. Cox proportional hazards models were used to compare outcome between the groups. Results. Two hundred patients were included and, based on the antimicrobial treatment, stratified in one long-term rifampicin group (n=23) or one of the three short-term rifampicin groups: clindamycin (n=56), flucloxacillin (n=47), vancomycin (n=26), other (n=48). Outcome of PJI after DAIR or one-stage exchange was not statistically different between patients treated with long-term rifampicin combination therapy and patients treated with clindamycin or flucloxacillin monotherapy including only five days of rifampicin combination therapy. Moreover, treatment duration was four weeks shorter in the clindamycin-based and flucloxacillin-based groups. Adjusted hazard ratios for failure for patients treated with either flucloxacillin or clindamycin were almost equal to patients treated with long-term rifampicin combination therapy (aHR 1.21, 95%CI 0.34–4.40). Conclusions. A short-term rifampicin strategy with either clindamycin or flucloxacillin and only five days of rifampicin was found to be as effective as traditional long-term rifampicin combination therapy. A randomized controlled trial is needed to further address efficacy and safety of alternative treatment strategies for staphylococcal PJI

Listeria monocytogenes is usually thought of as a bacterial pathogen that causes invasive disease including meningitis and bacteraemia in susceptible hosts. It remains a rare cause of bone and joint infection; there is therefore potential for clinical and laboratory delay in diagnosis and for uncertainty over optimal management. We describe our experience of two such cases of L. monocytogenes prosthetic joint infection to highlight key features in clinical presentation and management. Two case reports of L. monocytogenes prosthetic joint infection are described with reference to previous published cases. A 57 year old woman presented with a 10 day history of severe pain and swelling around a left knee prosthesis which had been implanted as bilateral total knee replacements three years previously. She had a background of rheumatoid arthritis, controlled with prednisolone, methotrexate and ritixumab. Cultures from the left knee isolated L. monocytogenes. The patient was commenced on IV amoxicillin and after 4 weeks underwent 1st stage revision including radical debridement and removal of prosthesis. During the procedure an antibiotic-impregnated spacer (gentamycin/clindamycin with additional vancomycin added in house) was inserted. Antibiotic therapy with intravenous amoxicillin was continued for 2 weeks post-procedure and on discharge the patient was converted to oral amoxicillin for a further 8 weeks. The patient went on to have a 2nd stage revision, making a good recovery. An 85 year old woman presented with an 18 month history of discomfort and recurrent abscesses along the wound line of a left hip prosthesis, implanted over 20 years ago. She had a background of osteoarthritis and bullous phemphigoid, previously on steroid treatment. Fluid from the abscess was aspirated and isolated L. monocytogenes. Due to patient preference and frailty, radical revision was not thought a viable management option. Chronic suppressive therapy with oral amoxicillin was therefore instigated; one year on the infection remains well controlled and discomfort in the left hip has improved. L. monocytogenes has previously been infrequently implicated as a pathogen in prosthetic joint infection; however, there are reports of increasing numbers of cases particularly amongst immunosuppressed individuals. With an expanding at-risk population(1), its importance as a cause of prosthetic joint infection is set to rise in the future. Optimal management has not been well studied; it is likely that the best option combines antimicrobial therapy and prosthetic removal if possible

Background. In the UK, over 160,000 total joint replacements are performed annually. About 1% of patients subsequently develop a deep bacterial infection and, if untreated, this can result in severe pain, disability, and death. Costs to the NHS are substantial. The INFORM (Infection Orthopaedic Management) programme aims to address gaps in knowledge relating to treatment of deep prosthetic joint infection through six work packages. The programme is supported by a patient forum and patient-partners working on oversight groups. Methods. Literature reviews and meta-analysis of individual patient data from cohort studies of patients treated for prosthetic hip infection. Analysis of the National Joint Registry to observe trends in infection rates, and identify risk markers for infection and effective treatments. Qualitative interviews with patients and health professionals exploring the impact of infection and its treatment. A multicentre randomised controlled trial to compare patient-centred outcomes after one- or two-stage revision for prosthetic hip infection. An economic evaluation to assess cost-effectiveness of treatments. A survey of patients to explore individuals’ preferences for treatments. Results. Individual patient data has been provided by UK and international centres. Data on over 1.4 million procedures is available from the National Joint Registry. Interviews conducted with 19 patients with prosthetic hip infection and 12 treating surgeons. Information has advised randomised controlled trial methodology. Seven major UK centres recruiting patients to the INFORM randomised controlled trial. Methods for assessment of costs from a health service and societal perspective developed for the randomised controlled trial. Qualitative studies have contributed to the design of a discrete choice questionnaire. Conclusions. Findings from INFORM will establish how patient care and outcomes can be optimised after prosthetic joint infection. Guidance on best clinical practice will be developed. Level of evidence 1–3. Funding statement This abstract presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (grant number: RP-PG-1210-12005). The views expressed in this abstract are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health

Aims. Prosthetic joint infections (PJIs) of the hip and knee are associated with significant morbidity and socioeconomic burden. We undertook a systematic review of the current literature with the aim of proposing criteria for the selection of patients for a single-stage exchange arthroplasty in the management of a PJI. Material and Methods. A comprehensive review of the current literature was performed using the OVID-MEDLINE, EMBASE, and Cochrane Library databases and the search terms: infection and knee arthroplasty OR knee revision OR hip arthroplasty OR hip revision, and one stage OR single stage OR direct exchange. All studies involving fewer than ten patients and follow-up of less than two years in the study group were excluded as also were systematic reviews, surgical techniques, and expert opinions. Results. The initial search revealed 875 potential articles of which 22 fulfilled the inclusion and exclusion criteria. There were 16 case series and six comparative studies; five were prospective and 14 were retrospective. The studies included 962 patients who underwent single stage revision arthroplasty of an infected hip or knee joint. The rate of recurrent infection ranged from 0% to 18%, at a minimum of two years’ follow-up. The rate was lower in patients who were selected on the basis of factors relating to the patient and the local soft-tissue and bony conditions. . Conclusion. We conclude that single-stage revision is an acceptable form of surgical treatment for the management of a PJI in selected patients. The indications for this approach include the absence of severe immunocompromise and significant soft-tissue or bony compromise and concurrent acute sepsis. We suggest that a two-stage approach should be used in patients with multidrug resistant or atypical organisms such as fungus

Aims. Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment. Methods. The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load. Results. PlySs2 treatment reduced 99% more CFUs and 75% more biofilm compared with vancomycin in vitro. A combination of PlySs2 and vancomycin in vivo reduced the number of CFUs on the surface of implants by 92% and in the periprosthetic tissue by 88%. Conclusion. PlySs2 lysin was able to reduce biofilm, target planktonic bacteria, and work synergistically with vancomycin in our in vitro models. A combination of PlySs2 and vancomycin also reduced bacterial load in periprosthetic tissue and on the surface of implants in a murine model of DAIR treatment for established PJI. Cite this article: Bone Joint J 2020;102-B(7 Supple B):3–10

INTRODUCTION. Deep infection is a potentially catastrophic complication of joint replacement surgery. Early intervention in suspected prosthetic joint infection in the form of aggressive Debridement and targeted Antibiotics can lead to successful Implant Retention (DAIR). In our centre, we adopt an aggressive approach to suspected prosthetic joint infection, working in a multi-disciplinary team with microbiologists and an infection surveillance team to identify and treat suspected infected cases at the earliest opportunity. OBJECTIVES. To evaluate the efficacy of the treatment of prosthetic joint infection with DAIR. METHODS. All cases of primary prosthetic joint infection between March 2009 and September 2011 were identified. Data was retrospectively collected from root cause analysis data, patient records and hospital electronic results systems. RESULTS. 48 cases of confirmed deep infection were identified from a total of 5037 primary joint replacements. Mean age was 67.3. The mean time between index procedure and return to theatre for debridement was 18 days. 10 patients underwent a second debridement and 3 returned to theatre for a third debridement. Mean total duration of antibiotic treatment was 10.5 weeks with mean duration of intravenous antibiotics 2.7 weeks. There were two early and three late failures on antibiotics. These went on to have successful two stage revision. The mean interval to debridement in failed cases was 15 days. The primary implant was successfully retained in 90% of cases (n=43) at a mean follow up of 30 months. CONCLUSION. DAIR is an effective means of treating early prosthetic joint infection in a multi-disciplinary setting

This study aimed to identify the success rate of debridement, antibiotics and implant retention (DAIR) for prosthetic joint infection (PJI) in a large prospective cohort of patients undergoing total knee arthroplasty (TKA). The ability for different PJI classification systems to predict DAIR success was assessed. A prospective, multicenter study of PJIs occurring between July 2014 and December 2017 in 27 hospitals across Australia and New Zealand was performed. First time PJIs following primary TKA that were managed with DAIR were analyzed. DAIR success was defined as the patient being alive with documented absence of clinical or microbiological evidence of infection and no ongoing antibiotics for the index joint at 2-year follow-up. Multivariate analysis was performed for multiple PJI classification systems to assess their ability to predict DAIR success using their respective definitions of “early” PJI (Coventry ≤1 month, International Consensus Meeting ≤90 days or Auckland <1 year), or as hematogenous versus chronic PJI (Tsukayama). 189 PJIs were managed with DAIR, with an overall success rate of 45% (85/189). Early PJIs had a higher rate of DAIR success when analyzed according to the Coventry system (adjusted odds ratio = 3.85, p = 0.008), the ICM system (adjusted odds ratio = 3.08, p = 0.005) and the Auckland system (adjusted odds ratio = 2.60, p = 0.01). DAIR success was lower in both hematogenous (adjusted odds ratio = 0.36, p = 0.034) and chronic PJIs (adjusted odds ratio = 0.14, p = 0.003) occurring more than one year since the primary TKA. DAIR success is highest when performed in infections occurring within one year of the primary TKA. Late infections had a high DAIR failure rate irrespective of their classification as hematogenous or chronic. Time since primary is a useful predictor of DAIR success

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

Introduction. The infection rate after total joint arthroplasty (TJA) has been shown to be 1–2% in multiple series and registry data. Irrigation, debridement, and polyethylene exchange (IDPE) is a common first line treatment in many cases of acute prosthetic joint infection (PJI). The reinfection rate in open IDPE procedures is variable with studies showing reinfection rates of 10–70% depending on various patient and microbial factors. Our pilot study aimed to determine if the bacterial load in infected total joints was sufficiently reduced by IDPE to allow for the use of post-debridement cultures as an independent marker of procedural success. Methods. 46 prosthetic joint infections underwent irrigation and debridement using 6L of normal saline and 3L of a normal saline and bacitracin mixture prior to the insertion of a new polyethylene liner. This protocol utilized a single equipment setup with all surgical members donning new gloves prior to polyethylene exchange. Between 3 and 5 intraoperative cultures were obtained both prior to and after debridement as per the surgeon's standard protocol. A two-tailed student's t-test was used to evaluate for any differences in the rate of positive culture between these two groups. Results. Of all pre- and post-debridement cultures sampled 66.5% and 60.7% of cultures were positive respectively. No significant difference in the rate of positive intraoperative culture was found between pre-debridement and post-debridement groups (p = 0.52). In 32 of 46 (69%) cases there was no difference in the total number of positive cultures despite a thorough debridement. Conclusions. Our data shows that open debridement of PJI does not provide a sterile environment, and post-debridement cultures should not be used as an independent marker of procedural success. The role of an irrigation and debridement to reduce the bacterial burden and potentiate the clearance of an infection is established but its efficacy is unclear, and the inability to create a post-debridement sterile environment is a concern

Aim. The aim of this study was to gain insight into the in vivo expression of virulence and metabolic genes of Staphylococcus aureus in a prosthetic joint infection in a human subject. Method. Deep RNA sequencing (RNA-seq) was used for transcriptome profile of joint fluid obtained from a patient undergoing surgery due to acute S. aureus prosthetic joint infection. The S. aureus gene expression in the infection was compared with exponential culture of a S. aureus isolate obtained from the same sample using EdgeR. In addition, the genome of the isolate was sequenced on Miseq, assembled in CLC genomics workbench and annotated by MaGe. Moreover, using nuclear magnetic resonance (NMR) spectroscopy we analysed the metabolites in the joint fluid and in the culture supernatants to determine the biochemical composition of the environments. Results. Antibiotic susceptibility testing by disk diffusion (EUCAST) demonstrated that the strain was susceptible to β-lactams (penicillin and cefoxitin) and macrolides (erythromycin and roxitromycin). This was indirectly confirmed by the annotated genome, because of absence of known resistant genes. The patient showed no signs of improvement during 2-days treatment with antibiotics (different β-lactams and gentamicin) prior to the surgery. The RNA-seq data indicated that the strategy employed by S. aureus to survive and proliferate in the host during antibiotic treatment involved overexpression of various enzymes related to cell-wall synthesis and multidrug efflux pumps. Interestingly, these efflux pumps are only known to be related to fluoroquinolone resistance. Many of the genes encoding virulence factors were upregulated, including toxins and superantigen-like proteins, hemolysins, and immune evasion proteins. A number of chaperones and stress related genes were overexpressed indicating a stress response. Furthermore, the RNA-seq data provided clues of the potential major nutrient sources for the pathogen in vivo. Several amino acid degradation pathways were highly upregulated, e.g. arginine, histidine. Additional carbon sources included N-acetylneuraminate and purine/pyrimidine deoxyribonucleosides as indicated by the upregulation of the genes involved in the degradation pathways of these compounds and higher concentration of these substances in the joint fluid compared to culture supernatants. Conclusions. Our results show that the gene expression pattern of S. aureusin vivo is vastly different from that of an in vitro grown exponential culture, indicating that the pathogen adapts to host environmental conditions by altering gene expression. Finally our study emphasizes the importance of in vivo study in elucidating pathogenesis of S. aureus in prosthetic joint infections

The infection rate after total joint arthroplasty (TJA) has been shown to be 1–2% in multiple series and registry data. Irrigation, debridement, and polyethylene exchange (IDPE) is a common first line treatment in many cases of acute prosthetic joint infection (PJI). The reinfection rate in open IDPE procedures is variable with studies showing reinfection rates of 10–70% depending on various patient and microbial factors. Our pilot study aimed to determine if the bacterial load in infected total joints was sufficiently reduced by IDPE to allow for the use of post-debridement cultures as an independent marker of procedural success. 46 prosthetic joint infections underwent irrigation and debridement using 6L of normal saline and 3L of a normal saline and bacitracin mixture prior to the insertion of a new polyethylene liner. This protocol utilized a single equipment setup with all surgical members donning new gloves prior to polyethylene exchange. Between 3 and 5 intraoperative cultures were obtained both prior to and after debridement as per the surgeon's standard protocol. A two-tailed student's t-test was used to evaluate for any differences in the rate of positive culture between these two groups. Of all pre- and post-debridement cultures sampled 66.5% and 60.7% of cultures were positive respectively. No significant difference in the rate of positive intraoperative culture was found between pre-debridement and post-debridement groups (p = 0.52). In 32 of 46 (69%) cases there was no difference in the total number of positive cultures despite a thorough debridement. Our data shows that open debridement of PJI does not provide a sterile environment, and post-debridement cultures should not be used as an independent marker of procedural success. The role of an irrigation and debridement to reduce the bacterial burden and potentiate the clearance of an infection is established but its efficacy is unclear, and the inability to create a post-debridement sterile environment is a concern

Introduction. In the last couple of years, several synovial biomarkers have been introduced in the diagnostic algorithm for a prosthetic joint infection (PJI). Alpha defensin-1 proved to be one of the most promising, with a high sensitivity and specificity. However, a major disadvantage of this biomarker is the high costs. Calprotectin is a protein that is present in the cytoplasm of neutrophils, and is released upon neutrophil activation. Its value has been established for decades as a (fecal) marker for inflammatory bowel disease. Aim. To determine the efficacy of synovial calprotectin in the diagnosis of a prosthetic joint infection. Methods. We prospectively collected synovial fluid (from hip, knee and shoulder) from patients with a proven PJI (n=15) and from patients that underwent a revision surgery without signs of a PJI (n=19). Patients with an active rheumatoid arthritis and/or gout were excluded from the study. Synovial fluid was centrifuged and the supernatant was used to measure calprotectin, by using a rapid, point of care test. This test was validated for synovial fluid analysis of calprotectin using an ELISA. A Mann-Whitney U test was used to calculate the difference between both patient groups. Results. The median calprotectin level was 899 mg/L (range 28–2120) for PJI versus 22 mg/L (range 0–202) for controls (p < 0.0001). With a cut-off value of 50 mg/L, synovial calprotectin has a high sensitivity of 93%, and a specificity of 84%. The positive and negative predictive values are 82% and 94%, respectively. Conclusions. Synovial calprotectin is a potentially valuable biomarker in the diagnosis of a PJI. With a point of care test, a rapid quantative diagnosis can be made within the operating room (results are obtained within 20 minutes), and could help in the decision making process to re-implant a prosthesis in a one stage procedure. In comparison to the currently available test (to measure alpha defensin-1), the measurement of calprotectin test is much cheaper (500 euro versus 20 euro per sample) and easily to implement in hospitals where this test is already available. Its diagnostic efficacy for exclusively low-grade PJI should be further elaborated