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

Prosthetic joint infection (PJI) is a severe complication of prosthetic joint implantation, with an estimated incidence of 2.18%. Most frequently used treatment strategy for PJI is a two-stage revision procedure. However there are specific patients with a new or persisting infection after primary or revision surgery where further surgical treatment is not attractive. This may be because of medical or local surgical conditions, or patient's refusal to undergo (further) surgical therapy. For these patients suppressive antibiotic therapy (SAT) may be an alternative treatment. The aim of this study is to describe the clinical and radiological outcome of patients with a PJI of a hip arthroplasty, treated with SAT. Twenty-four patients with a hip arthroplasty treated with suppressive antibiotic therapy for PJI between January 1, 2008 and December 31, 2013 were included. All patients had a proven prosthetic joint infection, either by ≥2 intraoperative cultures or joint aspiration. SAT was defined as treatment with antibiotic therapy for more than three months. Most used antibiotics were doxycycline in 15 patients and cotrimoxazole in six patients. Patients were supposed to have a successful outcome when their prosthesis remained in situ and they had no relapse or new infection. Suppressive antibiotic therapy was considered successful in 15 (62.5%) patients with a mean follow-up of 20.6 months. Two patients (8.3%) had to stop the antibiotic therapy due to adverse effects. The mean duration of the SAT was 20.4 months (range 0.92–92.65 months). Mean modified Oxford hip score of the successfully treated patients at the latest follow up was 35 (range 16–49) and mean Harris hip score 71 (range 40–93). The mean visual analogue scale (VAS) was 16 (range 0–70) in rest, 32 (range 0–85) during exercise and 65 (range 10–100) for satisfaction. Of the 9 patients with an unsuccessful outcome, there was a radiological loosening of the cup in 4 patients. In the group of 15 patients that were considered successful, 2 patients had a radiological loosening of the cup and one patient loosening of the stem. Suppressive antibiotic therapy can be an attractive alternative treatment in selected patients with a prosthetic joint infection of a hip arthroplasty who cannot or will not undergo (further) surgical therapy. Further research with a larger number of patients is required. Also the optimal dosage and duration of suppressive antibiotic therapy and possible resistance to the antibiotic therapy is unknown

Aims. The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Aims. We studied the impact of direct anterior (DA) versus non-anterior (NA) surgical approaches on prosthetic joint infection (PJI), and examined the impact of new perioperative protocols on PJI rates following all surgical approaches at a single institution. Patients and Methods. A total of 6086 consecutive patients undergoing primary total hip arthroplasty (THA) at a single institution between 2013 and 2016 were retrospectively evaluated. Data obtained from electronic patient medical records included age, sex, body mass index (BMI), medical comorbidities, surgical approach, and presence of deep PJI. There were 3053 male patients (50.1%) and 3033 female patients (49.9%). The mean age and BMI of the entire cohort was 62.7 years (18 to 102, . sd. 12.3) and 28.8 kg/m. 2. (13.3 to 57.6, . sd. 6.1), respectively. Infection rates were calculated yearly for the DA and NA approach groups. Covariates were assessed and used in multivariate analysis to calculate adjusted odds ratios (ORs) for risk of development of PJI with DA compared with NA approaches. In order to determine the effect of adopting a set of infection prevention protocols on PJI, we calculated ORs for PJI comparing patients undergoing THA for two distinct time periods: 2013 to 2014 and 2015 to 2016. These periods corresponded to before and after we implemented a set of perioperative infection protocols. Results. There were 1985 patients in the DA group and 4101 patients in the NA group. The overall rate of PJI at our institution during the study period was 0.82% (50/6086) and decreased from 0.96% (12/1245) in 2013 to 0.53% (10/1870) in 2016. There were 24 deep PJIs in the DA group (1.22%) and 26 deep PJIs in the NA group (0.63%; p = 0.023). After multivariate analysis, the DA approach was 2.2 times more likely to result in PJI than the NA approach (OR 2.2 (95% confidence interval 1.1 to 3.9); p = 0.006) for the overall study period. Conclusion. We found a higher rate of PJI in DA versus NA approaches. Infection prevention protocols such as use of aspirin, dilute povidone-iodine lavage, vancomycin powder, and Gram-negative coverage may have been positively associated with diminished PJI rates observed for all approaches over time. Cite this article: Bone Joint J 2019;101-B(6 Supple B):2–8

Aim. We aimed to compare the in vitro antibacterial activity of Bioactive Glass (BAG) S53P4, which is a compound showing local antibacterial activity, to that of antibiotic-loaded polymethylmethacrylate (PMMA) against multidrug resistant bacteria from osteomyelitis (OM) and prosthetic joint infection (PJI) isolates. Method. We studied convenience samples of multidrug resistant (MDR) microorganisms obtained from patients presenting OM and prosthetic joint infection (PJI). Mixtures containing tryptic soy broth (TSB) and inert glass beads (2mm), BAG-S53P4 granules (0.5–0.8mm and <45 mm) and Gentamicin or Vancomycin-loaded PMMA beads were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS), Pseudomonas aeruginosa or Klebsiella pneumoniae isolates. Glass beads (2.0mm) were used as a control. Antibacterial activity was evaluated by means of time-kill curve, through seeding the strains on blood agar plates, and subsequently performing colony counts after 24, 48, 72, 96, 120 and 168 hours of incubation. Differences between groups were evaluated by means of two-way analysis of variance (ANOVA) and Bonferroni's t test. Results. Inhibition of bacterial growth started soon after 48 hours of incubation, reached zero CFU/ml between 120 and 168 hours of incubation for both antibiotic-loaded PMMA and BAG S53P4 groups, in comparison with inert glass (p< 0.05). No difference regarding time-kill curves between antibiotic-loaded PMMA and BAG S53P4 was observed. Moreover, despite no difference was observed between both Vancomycin - or Gentamicin-loaded PMMA and BAG groups, there was statistical difference between the effectiveness of all treatments (BAG included) against gram-positive cocci and gram-negative bacilli, the latter of which requiring longer time frames for the cultures to yield no bacterial growth. Conclusions. BAG S53P4 presented antibacterial properties as much as antibiotic-loaded PMMA for MDR bacteria producing OM and PJI, although presenting differences between its effectiveness against different bacterial groups

Aim. European population is ageing concurrently with an increase number of arthroplasties. Prosthetic joint infection (PJI) in the elderly is considered more severe. The aim of this study is to describe PJI's management of patients over 79 years of age. Methods. We conducted a retrospective study including all patients aged over 79 years old consulting for a suspected hip or knee PJI in our community hospital where a complex bone and joint unit is present. Results. From 2007 to 2015, among the 366 patients who consulted for a PJI suspicion, 44 were older than 79. In this group, median age was 81.5 and 52% were women. A significant comorbidity was present in 24 patients among them 9 were diabetic. Location of suspected PJI was hip for 24 patients and 52% of the patients had a PJI background. Median time from the first arthroplasty was 8 years, however 17 had already an exchange. We classified the presentation as early (before 3 months after surgery, n=7), delayed (3 to 24 months, n=9) and late (more than 24 months, n=28). Pain was the first symptom, 9 presented fever and 10 had a sinus tract communication. Median C-reactive protein rate was 64 mg/l. Pre-operative synovial fluid analysis was performed in 34 patients, the concordance with intra-operative samples was 44%. A surgery was performed in 86% of the patients corresponding in five retentions, 17 one-time and 13 two-time exchange, 2 arthrodesis and one resection of arthroplasty. Coagulase-negative Staphylococcus (n=14), Staphylococcus aureus (n=10) and Enterobacteriaceae (n=5) were the principal microorganisms identified. Antibiotherapy median duration was 10 days for intravenous regimens and 45 days for total treatment. We noted 4 catheter-related infections and 9 side effects of antibiotics. A prolonged antibiotic suppressive therapy was performed for 8 patients (18%). With a median time of follow-up of 21.5 months, we notified 13 failures (30%) and 5 deaths (11%). After the episode, 5 patients could not standup, a walking stick was necessary for 11 patients, 2 for 5 patients while 13 recovered a relatively good autonomy. Conclusion. PJI in elderly people is a severe complication with a significant morbidity but palliative treatment is not the first alternative. We showed acceptable outcomes with more invasive managements. These data need to be compared with younger population in a second analysis

Cut-off values with highest sensitivity and specificity for the synovial fluid white cell and differential count will facilitate the accurate diagnosis of infection in total knee (TKR) and total hip replacement (THR). All patients undergoing revision TKR or THR for suspected prosthetic joint infection between 2009 and 2011 at two hospitals were identified. A total of 75 patients were included with a mean age of 70.3 years (38 to 89). Synovial fluid was aspirated pre-operatively and peri-prosthetic tissue samples were taken intra-operatively for histological and microbiological examination. Receiver operating characteristic (ROC) plots were constructed for white cell and differential counts in aspirated fluid. The optimal cut-off for TKR and THR was 1590 white cells/µl and 65% neutrophilia. The white cell count cut-off value identified for THR was notably lower than previously quoted in the literature. A cut-off value for white cell count in synovial aspirate in suspected prosthetic joint infection of between 1100 and 1700 white cells/µl is likely to be applicable to both THR and TKR. Cite this article: Bone Joint J 2013;95-B:554–7

Total hip arthroplasty (THA) is one of the most successful and effective treatments for advanced hip osteoarthritis (OA). Over the last 5 years, Canada has seen a 17.8% increase in the number of hip replacements performed annually, and that number is expected to grow along with the aging Canadian population. However, the rise in THA surgery is associated with an increased number of patients at risk for the development of an infection involving the joint prosthesis and adjacent deep tissue – periprosthetic joint infections (PJI). Despite improved hygiene protocols and novel surgical strategies, PJI remains a serious complication. No previous population-based studies has investigated PJI risk factors using a time-to-event approach and none have focused exclusively on patients undergoing THA for primary hip OA. The purpose of this study is to determine risk factors for PJI after primary THA for OA using a large population-based database collected over 15 years. Our secondary objective is to determine the incidence of PJI, the time to PJI following primary THA, and if PJI rates have changed in the past 15 years. We performed a population-based cohort study using linked administrative databases in Ontario, Canada in accordance with RECORD and STROBE guidelines. All primary total hip replacements performed for osteoarthritis in patients aged 55 or older between January 1st 2002 – December 31st 2016 in Ontario, Canada were identified. Periprosthetic joint infection as the cause for revision surgery was identified with the International Classification of Diseases, 10th Edition (ICD-10), Clinical Modification diagnosis code T84.53 in any component of the healthcare data set. Data were obtained from the Institute for Clinical Evaluative Sciences (ICES). Demographic data and outcomes are summarized using descriptive statistics. We used a Cox proportional hazards model to analyze the effect of surgical factors and patient factors on the risk of developing PJI. Surgical factors include the approach, use of bone graft, use of cement, and the year of surgery. Patient factors include sex, age at surgery, income quintile and rurality (community vs. urban). We compared the 1,2,5 and 10 year PJI rates for patients undergoing THA each year of our cohort with the Cochran-Armitage test. Less than 0.1% of data were missing from all fields except for rurality which was lacking 0.3% of data. A total of 100,674 patients aged 55 or older received a primary total hip arthroplasty for osteoarthritis from 2002–2016. We identified 1034 cases of revision surgery for prosthetic joint infection for an overall PJI rate of 1.03%. When accounting for patients censored at final follow-up, the cumulative incidence for PJI is 1.44%. Our Cox proportional hazards model revealed that male sex, Type II diabetes mellitus, discharge to convalescent care, and having both hips replaced during one's lifetime were associated with increased risk of developing PJI following primary THA. Importantly, the time adjusted risk for PJI was equal for patients operated within the past 5 years, 6–10 years ago, or 11–15 years ago. The surgical approach, use of bone grafting or cement were not associated with increased risk of infection. PJI rates have not changed significantly over the past 15 years. One, two, five and ten-year PJI rates were similar for patients undergoing THA in all qualifying years. Analysis of a population-based cohort of 100,674 patients has shown that the risk of developing PJI following primary THA has not changed over 15 years. The surgical approach, use of bone grafting or cement were not associated with increased risk of infection. Male sex, Type II diabetes Mellitus and discharge to a rehab facility are associated with increased risk of PJI. As the risk of PJI has not changed in 15 years, an appropriately powered trial is warranted to determine interventions that can improve infection rate after THA

Aim. One of the most accurate and inexpensive tests in detection of prosthetic joint infection (PJI) is synovial fluid white blood cell (WBC) count and differential. Since leukocytes produce many different interleukins (IL) in situation of PJI, we hypothesized that ILs could be even more accurate in detection of PJI. The aim of the study was to test, if the synovial fluid IL-6 level is superior to WBC count and differential in detection of PJI. Methods. Unselected patients undergoing total hip or knee revision surgery were prospectively included. In perioperative assessment phase, WBC count, differential and IL-6 levels of synovial fluid were measured. Patients were labelled as positive or negative according to the predefined cut-off values for IL-6 (230pg/ml) and WBC count with differential (1,7 × 10. 9. WBC/ml with ≥65% of granulocytes). During the surgery, at least 4 intraoperative samples for microbiological and one for histopathological analysis were obtained. PJI was defined as presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in at least two or more samples of periprosthetic tissue or synovial fluid. Binary diagnostic test was performed to check the diagnostic strength of both methods in detection of PJI. Results. 49 joints of 48 patients (mean age, 71 years; 53% females) undergoing artificial hip (n = 24) or knee (n = 25) revision surgery were included. 11 joints (22%) were infected. Sensitivity of synovial fluid WBC count with differential was 82%, specificity 97%, accuracy 94%, positive and negative predictive values were 90% and 95%, respectively. Sensitivity of IL-6 level was 73%, specificity 95%, accuracy 90%, positive and negative predictive values were 80% and 92%, respectively. There was a strong statistical agreement between both tests (Kappa value=0.749) and consequently there was no significant difference in detection of PJI comparing both tests (P=0.171). Conclusion. Our study revealed that synovial fluid IL-6 level is not superior to synovial fluid WBC count with differential in detecting PJI

Introduction. Fluorodeoxuglucose(FDG) Positron Emission Tomography(PET) scan is used in the diagnosis of prosthetic joint infection, when the inflammatory markers and aspiration of the joint do not establish a definitive diagnosis. The aim of our study was to analyse the utility of FDG PET scan in decision making in these patients. Methods. We performed a prospective study of patients who underwent a FDG PET scan for suspected prosthetic hip infection, between September 2013 and July 2017. We analysed the results of aspiration, culture and sensitivity, histology of intra-operative samples and inflammatory markers. Our gold standard for diagnosis of infection was 3 or more positive cultures of the same organism. Diagnostic utility statistics for FDG PET were performed. Results. 55 revisions total hip replacements were included. The mean age of the patients was 67.5±4.85 years. The mean ESR, CRP and WCC were 19.83 mm/hr, 22.21 mg/l and 9.05×10. 9. /l respectively. The sensitivity and specificity for FDG PET were 93.75% and 35.89% respectively. The positive predictive value(PPV) was 37.5% and negative predictive value(NPV) was 93.33%. The accuracy of detecting an infection was 52.7%. The false positive rate was 62.5%. Discussion. FDG PET has a large number of false positive results and low specificity. If the inflammatory markers and aspiration do not establish infection, addition of FDG PET has limited accuracy in confirming the diagnosis of prosthetic joint infection. Conclusion. FDG PET may be useful for ruling out infection, but a positive result may not indicate the presence of infection

Objectives. Investigate the incorporation of an antibiotic in bone cement using liposomes (a drug delivery system) with the potential to promote osseointegration at the bone cement interface whilst maintaining antibiotic elution, anti-microbiological efficacy and cement mechanical properties. Prosthetic joint infection and aseptic loosening are associated with significant morbidity. Antibiotic loaded bone cement is commonly used and successfully reduces infection rates; however, there is increasing resistance to the commonly used gentamicin. Previous studies have shown gentamicin incorporated into bone cement using liposomes can maintain the cement's mechanical properties and improve antibiotic elution. The phospholipid phosphatidyl-l-serine has been postulated to encourage surface osteoblast attachment and in a liposome could improve osseointegration, thereby reducing aseptic loosening. Preliminary clinical isolate testing showed excellent antimicrobial action with amoxicillin therefore the study aims were to test amoxicillin incorporated into bone cement using liposomes containing phosphatidyl-l-serine in terms of antibiotic elution, microbiological profile and mechanical properties. Methods. Amoxicillin was encapsulated within 100nm liposomes containing phosphatidyl-L-serine and added to PMMA bone cement (Palacos R (Heraeus Medical, Newbury, UK)). Mechanical testing was performed according to Acrylic Cement standards (ISO BS 5833:2002). Elution testing was carried out along with microbiological testing utilising clinical isolates. Results. Liposomal encapsulated amoxicillin PMMA bone cement exceeded minimum ISO BS 5833:2002 standards, had better elution at 12.9% when compared with plain amoxicillin (p=0.036 at 48 hours) or commercial gentamicin cement (Palacos R+G, Heraeus Medical, Newbury, UK – previous studies showed 6% elution over the same time period). Amoxicillin showed superior antimicrobial action when compared with gentamicin of the same concentration. However, liposomal encapsulated amoxicillin in solution and liposomal encapsulated amoxicillin in PMMA were both less effective than free amoxicillin in bacterial growth inhibition. The liposomal amoxicillin also seemed to decrease the cement setting time. Conclusions. Phosphatidyl-l-serine containing liposomes maintained the cement's mechanical properties and seemed to have better antibiotic elution, however, had less effective antibacterial action than plain amoxicillin. This difference in antibacterial action requires further investigation along with investigation of osteoblast attachment to phosphatidyl-l-serine containing liposomes within cement. Plain amoxicillin, for those not penicillin allergic, seems to be a credible alternative to gentamicin for incorporation in PMMA bone cement. It has shown superior antibacterial action, which may improve infection rates, whilst maintaining the cement's mechanical properties

Introduction. Prosthetic joint infection (PJI) is the leading cause of failure of primary and revision hip and knee arthroplasty. It is challenging condition which represents a growing burden on hospital resources. In-patient hospital stay for antibiotic therapy post-operatively is costly and access to out-patient IV therapy (OPAT) varies between regions. In a tertiary referral centre for revision and infection, the suitability and cost-effectiveness of Dalbavancin was reviewed as a “single-shot” therapy following DAIR or revision lower limb arthroplasty for PJI. Methods & Materials. A prospective service evaluation was carried out for consecutive patients treated for PJI of the hip or knee who received Dalbavancin. Treatment was indicated by Consultant Microbiologist advice within an MDT setting where clinical or patient factors made alternative therapies eg. OPAT inappropriate. Service-level data was collected to allow calculation of bed-day savings compared to a traditional 14-day course of IV treatment. Readmission rates to the trust within 30 days were reviewed as a marker of clinical efficacy and safety. Results. 12 patients received dalbavancin for PJI. Mean bed-day saving was 6.9 (SD 3.7) per patient. A total of 83 bed days were saved compared to traditional treatment and there was a modest cost-benefit. There were no adverse reactions noted and no readmissions within 30 days. Discussion. The safety and efficacy of dalbavancin has been demonstrated in recent literature, but the impact that it can have on health-care costs and in-patient burden has not been explored. In addition, the success of out-patient therapy relies on patient engagement. In patients with co-existing cognitive difficulty or alcohol/substance use Dalbavancin offers an attractive alternative. Conclusions. The results of our pilot suggest that IV Dalbavancin is cost-effective as part of the treatment strategy for PJI and can lead to significant bed-day savings, which can assist in patient flow and departmental efficiency

Introduction. The intra-operative diagnosis of Prosthetic Joint Infection (PJI) is a dilemma requiring intra-operative sampling of suspicious tissues for frozen section, deep tissue culture and histopathology to secure a diagnosis. Alfa defensin-1 testing has been introduced as a quick and reliable test for confirming or ruling out PJI. This study aims to assess its intra-operative reliability compared to the standard tests. Methods. Twenty patients who underwent revision hip and knee arthroplasty surgery were included. Patients joint aspirate was tested intra-operatively with the Synovasure kit, which takes approximately ten minutes for a result. Our standard protocol of collecting 5 deep tissue samples for culture and one sample for histopathology was followed. Results for Alfa defensin-1 test were then compared with final culture and histopathology results in all these patients. Results. Our results show an excellent correlation with the final deep tissue cultures and histopathology outcomes. Literature reports frozen section to have low (58–73%) sensitivity but high (96%) specificity. Conclusions. Alfa defensin-1 test is easy, quick and efficient; results were available immediately intra-operatively. Cryosection is time consuming with samples shipped to the reference laboratory at times resulting in intra-operative delays. In our practice Alfa defensin-1 test certainly will replace frozen section for intra-operative testing

Aim. Revision surgery and debridement and implant retention are recognised approaches for managing prosthetic joint infections (PJI) but may not always be indicated. If the patient is unable to have or declines surgery, prolonged suppressive antibiotic therapy (PSAT) is an option. This study aims to define outcomes of PSAT from a single unit. Method. A retrospective study was performed. All cases of PJI involving the hip or knee between 2012 and 2017 were identified from our institutional database and cross referenced with patient notes. One hundred and seventy eight cases were identified. Of these, 23 (12.9%) (10 hips, 13 knees) were treated with PSAT. Infection was diagnosed based on the MSIS criteria in all cases and all cases were managed by a multidisciplinary team which included specialist microbiologists. One case of long term antifungal therapy was additionally identified. Co-morbidity was assessed using the Charlson co-morbidity index. Exacerbations of infection and need for further surgery were recorded. Results. The mean age was 72 years (Range 35–93 years). The mean Charlson-score was 4.3 (range 1–7). Mean follow up was 24 months (Range 1–54 months). Antibiotics were commenced within 3 months of surgery in 20 cases and between 2 and 4 year following surgery in the remainder. Prolonged antibiotic therapy followed debridement and implant retention in 12 cases, single stage revision in 4 cases and 2 stage revisions in 3 cases. The average number of surgical procedures undergone by each patient prior to starting antibiotic suppression therapy was 1.8 (Range 1–4 procedures). Staphylococcal species were isolated in 13 cases (MRSA 1, MSSA 5, Staph. Epidermidis 5, CONS 1, Staph Pasteuri 1). Escherichia Coli and Streptococci were isolated in 2 cases each. Four cases were due to polymicrobial infection. No organisms were identified in 2 cases. Candida Albicans was identified in 1 case. All cases of infection were treated with prolonged oral antibiotics. Twenty patients (87%) received 6 weeks of intravenous antibiotics prior to commencing prolonged oral antibiotics. Two patients experienced persistent symptoms and required amputation (both TKA). One immunocompromised patient required admission for sepsis related to their infected TKA. The success rate of long term suppressive antibiotics was 87% (20/23) successful at an average 2 year follow up. There was persistent wound discharge in 1 case (4.3%). Conclusions. Prolonged suppressive antibiotic therapy is an effective option for management of PJI and related symptoms with a low incidence of complications in surgically resistant PJI

Aim. To assess the analytical performance and to establish the cut-off of synovial fluid D-lactate concentration for the diagnosis of prosthetic joint infection (PJI) and septic arthritis (SA) using commercial kits provided by two manufacturers (A and B). Method. We prospectively included patients with native or prosthetic joints undergoing synovial fluid aspiration as routine diagnostic procedure. Among 224 patients with prosthetic joints, 137 patients had aseptic loosening (AL) and 87 were diagnosed with PJI. Among 71 patients with native joints, 39 were diagnosed with osteoarthrosis (OA) and 32 with SA. Results. Kits for the measurement D-lactate provided by the manufacturer A. Patients with prosthetic joints. The mean D-lactate concentration was significantly higher in patients with PJI than with AL (2.33 vs 0.77 mMol, respectively; p<0.0001). The optimal D-lactate cut off was 1.2 mmol/l (sensitivity = 97.7%, specificity = 83.9%, PPV = 79.4%, NPV = 98.3%; AUC = 0.99). Patients with native joints. We found significantly higher concentration of D-lactate in patients with SA compared to OA (2.27 vs 0.46 mMol, respectively; p<0.0001). The optimal D-lactate cut off was 1.2 mmol/l (sensitivity = 93.8%, specificity = 94.9%, PPV = 93.7%, NPV = 94.9%; AUC = 0.99). Kits for the measurement D-lactate provided by the manufacturer B. Patients with prosthetic joints. The difference between concentration of D-lactate in patients with PJI and AL was also significant (mean, 2.5 vs 0.04 mmol/L, respectively; p<0,0001). The optimal D-lactate cut off was 0.5 mmol/L (sensitivity = 94.7%, specificity = 92,0%, PPV = 85.7%, NPV = 97.1%; AUC = 0.99). Patients with native joints. Significantly higher concentration of D-lactate in patients with SA in comparison with OA (mean, 2.0 vs 0.28 mmol/L, respectively; p<0.0001). The optimal D-lactate cut off was 0.5 mmol/L (sensitivity = 100%, specificity = 92.0%, PPV = 81.8%, NPV = 100%; AUC = 0.99). Conclusions. The synovial fluid D-lactate test shows high analytical performance and diagnostic capabilities in the diagnosis of PJI and SA. The optimal cut-off for the diagnosis of infection differ between manufactures. Synovial fluid D-lactate is reliable bacterial-specific marker for diagnosis of PJI and SA

Aims. The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. Patients and Methods. We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. Results. Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. Conclusion. PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9–15

Deep infection represents one of the most devastating complications of total knee arthroplasty. Commonly implicated organisms are gram positive bacteria such as staphylococcus aureus, staphylococcus epidermidis and group B streptococcus. Occasionally, infection may be caused by rare organisms, particularly in the immunocompromised host. We present a case of infected total knee arthroplasty in a penicillin allergic patient, caused by Pasteurella multocida, 13 weeks after the initial surgery. This was treated by open debridement and change of insert as well as aggressive antibiotic therapy. The patient admitted contact with a cat and three dogs at home. Pasteurella multocida is a facultatively anaerobic gram negative coccobacillus. It is a commensal in the nasopharygeal tract of domestic pets such as cats and dogs. Human infection can often be attributed to a bite or scratch. Prosthetic joint infection caused by Pasteurella is uncommon. Only a few cases have been reported in the literature. Our case has several learning points: (1) It is very important to definitively identify Pasteurella because standard therapy for prosthetic joint infection (e.g. flucloxacillin or vancomycin) is not optimal for this species.(2) Pasteurella are susceptible to penicillin, but the optimal antibiotic therapy for infections in patients allergic to beta lactam antibiotics is uncertain. A combination of ciprofloxacin and linezolid is recommended. (3) There is no consensus regarding appropriate management. There are reports of washout and antibiotic therapy alone, single and two stage revision procedures. In our case, at five months follow up, open debridement and change of insert along with antibiotic treatment appears to have been effective, although more long term follow up is required. (4)Post arthroplasty, all patients with pets at home should be advised to seek medical attention following any bite or scratch so that timely prophylaxis can be administered before sepsis becomes deep-seated

Aim. To study whether revision for prosthetic joint infection (PJI) after early PJI in primary Total Hip Arthroplasty (THA) is associated with a high mortality, when compared with:. Patients, who did not undergo revision for any reason and Patients who underwent an aseptic revision. Method. This population-based cohort study was based on the Danish Hip Arthroplasty Register on primary THA performed in Denmark from 2005 to 2014. Data from the Danish Hip Arthroplasty Register were linked to microbiology databases, the National Register of Patients, and the Civil Registration System to obtain data on microbiology, comorbidity, and vital status on all patients. The mortality risk for the patients who underwent revision for PJI within 1 year from implantation of primary THA was compared with (1) the mortality risk for patients who did not undergo revision for any reason within 1 year of primary THA; and (2) the mortality risk for patients who underwent an aseptic revision. Results. A total of 68,504 primary THAs in 59,954 patients were identified, of those 445 primary THAs underwent revision for PJI, 1350 primary THAs underwent revision for other causes and the remaining 66,709 primary THAs did not undergo revision. Patients were followed from implantation of primary THA until death or 1 year of follow-up, or, in case of a revision, 1 year from the date of revision. Within 1 year of primary THA, 8% (95% CI, 6%–11%) of patients who underwent revision for PJI died. The adjusted relative mortality risk for patients with revision for PJI was 2.18 (95% CI, 1.54–3.08) compared with the patients who did not undergo revision for any cause (p < 0.001). The adjusted relative mortality risk for patients with revisions for PJI compared with patients with aseptic revision was 1.87 (9f5% CI, 1.11–3.15; p = 0.019). Patients with enterococci-infected THA had a 3.10 (95% CI, 1.66–5.81) higher mortality risk than patients infected with other bacteria (p < 0.001). Conclusions. Revision for PJI within 1 year after primary THA induces an increased mortality risk during the first year after the revision surgery. Especially enterococci-infected THA have a high motrtaly risk

Aim. We report on the performance of a simple algorithm using a combination of synovial fluid White blood cell count(WBC), C-reactive protein(CRP) and α-Defensin(AD) tests to aid in the diagnosis of prosthetic joint infections. Methods. Sixty-six synovial fluid samples were collected prospectively in patients with suspected PJI (hip and knee). All samples were tested by: WBC counts (read manually) and CRP test (Alere-Afinion™ validated in-house); and on 37 of these with AD test. Synovial fluid samples were collected in 5 ml ethylenediaminetetraacetic acid (EDTA) tubes. Samples that were very viscous were pre-processed by the addition of 100µl of hyaluronidase solution. Grossly blood stained and clotted samples were excluded. A clinical diagnosis of infection was based IDSA definitions. 1. Cut offs of >3000 × 10. 6. cells/L for total synovial WBC count and >12mg/L for CRP were used to define infection. 2,3. . Results. Of 66 samples tested, 20 samples were categorised as clinically infected. Combination of WBC count and CRP yielded a sensitivity of 95% (95% CI: 75.13% to 99.87%) and specificity of 100% (95% CI: 92.29% to 100.00%). Only one patient, who had a chronic infection with S.epidermidis and S.warneri, had a CRP and WBC count that was falsely negative (<5mg/L and 93 × 10. 6. cells/L respectively). AD test was used on 37 samples (of which 20 were infected). Sensitivity of this test alone was 85.71% (95% CI: 63.66% to 96.95%) and specificity 87.5% (95% CI: 61.65% to 98.45%). There were 2 falsely positive AD test results (one of whom had a metal on metal prosthesis) and 3 false negative results (2 E.coli infections and one patient with chronic infection with S.epidermidis and S.warneri). Conclusion. Use of a combination of synovial fluid WBC count and CRP (both of which can be performed using simple and inexpensive laboratory tests), has a sensitivity of 95% and 100% specificity in the diagnosis of PJI. AD test may be useful on some occasions when near patient testing result may affect patient management

Aim. Phage therapy has attracted attention as a promising alternative treatment option for biofilm infections. To establish a successful phage therapy, a comprehensive stock of different phages covering a broad bacterial spectrum is crucial. We screened human and environmental sources for presence of lytic phages against selected bacteria. Methods. Saliva collected from 10 volunteers and 500 ml of sewage water were screened for the presence of lytic phages active against 20 clinical strains of Staphylococcus aureus and 10 of Escherichia coli, both isolated from patients with prosthetic joint infection. Laboratory strains of methicillin-resistant S. aureus (MRSA)*1 and E. coli*2 were also tested. Screening was performed plaque-assay to detect phages for different strains. Isolated plaques were collected and phages were enriched to determine their activity against their bacterial host strains. The activity of bacteriophages against adherent E. coli and MRSA was evaluated by crystal violet, staining bacterial biofilms grown on glass beads. Results. Six bacteriophages specific for MRSA were isolated from saliva. Bacteriophages for E. coli strains were isolated from sewage water (n=3) and saliva (n=1). All bacteriophages tested against biofilms of their bacterial host showed a reduction of the total biomass (ranging from 19% to 84%). Conclusions. Both sewage and saliva samples provided bacteriophages specific against selected bacterial strains. 24h phage treatment of E. coli and S. aureus biofilms lead to a reduction but not to a complete eradication of biofilm

Joint replacement is a life-enhancing, cost-effective surgical intervention widely used to treat disabling joint pain mainly caused by osteoarthritis. Hip and knee joint replacements are common, highly successful operations bringing many patients relief from pain, and improve mobility. Prosthetic joint infections (PJI) are often difficult to diagnose; diagnosis often relying on a combination of clinical findings, microbiological data and histological evaluation of periprosthetic tissue. The majority of recent studies demonstrate a higher sensitivity for the culture of sonication fluid (62–94%) than periprosthetic tissue (55–88%). The Royal Devon & Exeter NHS Foundation Trust provided a specialist multidisciplinary team. We evaluated the use of sonication for identifying pathogens during revision hip and knee replacement in our unit with the intention of applying for further grants to study this technology in more detail; it was a diagnostic feasibility study. The target recruitment was 50 patients; 25 consecutive patients undergoing revision hip arthroplasty for any reason, and 25 undergoing revision knee arthroplasty for any reason. The majority of patients were identified in outpatient clinics. Our results show that tissue culture remains more sensitive than sonication. The sensitivity for direct sonication was 75% compared with 80% for tissue culture; sensitivity of enriched sonication was 80 %, compared to the unit results for tissue culture of 83%. The combined sensitivity of tissue culture was better as a higher number of tissue specimens were obtained. The different methodology might explain reported differences between this and other studies; however, our study does not support the use of sonication as the only tool in the diagnosis of PJI

Aim. Pre-operative distinction between prosthetic joint infections (PJI) and non-infectious causes of joint failure is particularly challenging, especially in chronic situations. Guidelines propose different algorithms using numerous preoperative tests. We evaluated place of serology. Method. During a 9 month period, we included consecutive patients undergoing arthroplasty revision for a suspected chronic hip or knee infection. Serologies were sampled at the same day than the other blood tests. Results were compared with the final diagnosis, determined with peroperative bacteriological and histological results. Serology was performed using a multiplex antibody detection*. This multiplex antibody detection assay detects antibodies against Staphylococcus species, Propionibacterium acnes and Streptococcus agalactiae. Results. A total of 52 patients were enrolled. Median time from last arthroplasty was 30 months (extremes 8 months − 17 years). Median clinical signs duration was 6 months (extremes 1 – 40 months). Median CRP value was 6 mg/l (extremes 2 – 150) and sedimentation rate 12 mm (extremes 2 – 82). Diagnostic of PJI was finally retained for 17 patients and ruled out for 35. It was Staphylococcus aureus 3 times, coagulase negative staphylococci (CoNS) 5 times, P. acnes 4 times, candida sp. 2 times, Streptococcus agalactiae one time, Enterobacter cloacae one time and undetermined one time. Serology was concordant and accurate with the final diagnosis for 38 patients (27 sterile and 11 infected). For 7 of them, serology was the key parameter. In these cases, a CoNS or a P. acnes was isolated per-operatively on a single culture, out of 5 samples. Serology allowed confirming a contamination in 5 cases; and in 2 cases, even if not fulfilling the definition, it determined a PJI. In this study, serology had a global sensitivity of 65%, 77% specificity, 58% positive predictive value, and 82% negative predictive value. Serology reached 89% sensitivity with unchanged specificity in the subgroup of 11 patients with a CRP > 10 mg/l. Conclusions. We evaluated place of serology in the most complex cases of suspected chronic PJIs, with finally, only 33% cases with an infection. Modest results of serology can be explained because antigens included in the assay were not those expressed in sessile bacteria. And by persistence of a humoral response, witnesses of past infections, for patients who had past surgeries on the joint. However, simple and practical, when combined with all other parameters, serology could provide a valuable support in preoperative evaluation of chronic PJIs. * BJI InoplexTM

Aim. Early prosthetic joint infection (PJI) is a feared complication of hip arthroplasty. Debridement, antibiotics and implant retention (DAIR) is attempted to avoid removal of the implant. The aim of this retrospective cohort study was to evaluate the success rate of DAIR in early PJI. Method. All patients who were diagnosed with early PJI and treated with DAIR at our center from 2003 to 2013 were included in the study. During the time period, 5176 primary hip arthroplasties and 555 revision hip arthroplasties were performed. Early PJI was diagnosed in 54 patients (43 primary and 11 revisions). Median follow-up was 5.6 years (range 2.0–12.1). Standard postoperative antibiotic treatment at our centre is vancomycin and rifampicin. Results. Median patient age was 74 years and 29 patients were women. Mean C-reactive protein at time of diagnosis was 119 mg/L (range 4–546). In 41 patients the infection was eradicated with one DAIR median 17.6 days (range 5–44) after index surgery. Twelve patients underwent a second DAIR and two patients needed DAIR 3 times. Eight primary arthroplasties and two revision arthroplasties proceeded to 2-stage revision after index surgery. Two patients (revisions) were left with a spacer only and one patient was put on lifelong antibiotic suppression therapy. The most frequently isolated microorganisms were Staphylococcus aureus in 19 patients (35%) and Coagulase negative Staphylococcus in ten patients (19%) of which five were MRSE. There were no infections with MRSA in our material. Among the ten patients that proceeded to 2-stage revision, five had Staphylococcus aureus, three had polymicrobial flora, one Coagulase negative Staphylococci and one Propionebacterium acnes infection. The most frequently used post-operative parenteral antibiotic treatment was vancomycin in 35 patients and cloxacillin in 15 patients. The subsequent oral treatment was predominantly dicloxacillin in 25 patients and ciprofloxacin in ten patients. Twenty-four patients received rifampicin in addition. These were mainly patients operated after 2009. Intravenous antibiotics were given for median 15.7 days (range 0–60) and continued orally for median 8.1 weeks (range 0–72). Conclusions. In our cohort of 54 patients, 81.4% of primary prothesis and 63.6% of the revision prosthesis were treated successfully with DAIR. This is in accordance with previous studies

Aim. The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading to propose cefepim as an alternative since 2017 in our reference center. The present study compared microbiological efficacy and tolerance of these two EAT strategies. Method. All patients with PJI empirically treated by vancomycin-cefepim (n=90) were prospectively enrolled in an observational study, and compared with vancomycin-piperacillin/tazobactam-treated historical controls (n=117), regarding: i) the proportion efficacious empirical regimen (i.e., at least one of the two molecules active against the identified organism(s) based on in vitro susceptibility testing); and ii) the incidence of empirical therapy-related adverse events (AE), classified according to the Common terminology criteria for AE (CTCAE). Results. Among the 146 (67.3%) documented infections, the EAT was considered as efficacious in 99 (99.0%) and 66 (98.5%) in the piperacillin-tazobactam and cefepim-treated patients, respectively (p=0.109). The rate of adverse events, and in particular AKI, was significantly higher in the vancomycin-piperacillin/tazobactam (n=38 [32.5%] and 32 [27.6%]) compared to the vancomycin-cefepim (n=13 [14.4%] and 5 [5.7%]) group (p=0.003 and <0.001, respectively). Of note, sex, age, and the proportion of patients receiving other nephrotoxics were similar among piperacillin/tazobactam- and cefepim-treated patients. However, in comparison with patients receiving cefepim, a higher modified Charlson's comorbitidy index (4 [IQR, 3–5] versus 2 [IQR, 2–4], p<0.001) has to be acknowledged, mainly related to a higher prevalence of baseline chronic renal injury (n=62, 53.4% versus n=34, 38.6%; p=0.035). Conclusions. The empirical use of vancomycin-cefepim in PJI was as efficient as vancomycin-piperacillin/tazobactam, and was associated with a significantly lower incidence of AKI

Background. Smoking has been associated with poor tissue oxygenation and vascularisation, predisposing smokers to a higher risk for postsurgical infections. The aim of this study was to estimate and compare the incidence of prosthetic joint infection (PJI) following primary total joint arthroplasty (TJA) according to smoking status. Methods. A prospective hospital-registry based cohort was used including all primary total knee and hip arthroplasties performed between 03/1996 and 12/2013 and following them until 06/2014. Smoking status at time of surgery was classified in never, former and current smoker. Incidence rates and incidence rate ratios (IRR) for PJI according to smoking status were assessed within the first year and over the whole study period. Adjusted IRRs were obtained using cox regression model. Adjustment was performed for the following baseline characteristics: age, sex, BMI, ASA score, diabetes, arthroplasty site (knee or hip) and surgery duration. Results. We included 8,559 TJAs, 3,361 knee and 5,198 hip arthroplasties. Mean age was 70 years, 61% were women, mean follow-up time was 77 months. 5,722 were never (group 1), 1,315 former (group 2) and 1,522 current (group 3) smokers. Over the study period, 108 PJI occurred. Incidence rates of infection within one year were for group 1, 2 and 3, respectively: 4.7, 10.1 and 10.9 cases/1000 person-year. Comparing ever- vs. never-smokers, the adjusted IRR was 1.84 (95% CI 1.05–3.2). Incidence rates for infection over the whole study period were 1.5, 3.1 and 2.7 cases/1000 person-years for group 1, 2 and 3, respectively. Adjusted IRR for ever- vs. never-smokers was 1.46 (95% CI 0.97–2.19). Conclusions. Smoking was associated with an about 1.5 times higher incidence rate of PJI following TJA. The difference was established already in the first year after surgery and remained thereafter. Level of Evidence. prospective registry based comparative cohort study (level II)

Aim. Debridement, antibiotics and implant retention (DAIR) has become the preferred treatment in early prosthetic joint infections (PJI) and acute haematogenous PJI, but the success rates have been varying. The aim of this study was to evaluate the outcome of a high quality DAIR procedure performed according to a consistently applied surgical protocol in early PJI's and acute haematogenous PJI's in hip and knee. Methods. We performed a prospective multicentre study in 8 hospitals in Norway. A standardized DAIR protocol was used in all patients. An empirical intravenous regimen containing cloxacillin and vancomycin was given until definitive microbiological results were known. Antibiotics were given in total for 6 weeks. The primary outcome measure was infection control. Factors that could affect the outcome were also studied. Results. Out of 99 patients included, 82 were finally analysed. 68/82 patients were successfully trreated (82,9% (CI: 74,4%-90,2%)). We found that DAIR following an infected revision arthroplasty was associated with poor outcome (59%) compares to DAIR following a primary arhroplasty (89%, p=0,007). Conclusion. The success rate of a standardized DAIR-procedure with 6 weeks of antibiotic treatment was good in PJI following primary prosthesis. The success rates following revision surgery infections are poor, and other treatment options should be considered

Although there is still no absolute diagnostic test for infection of the prosthetic joint, the synovial fluid leukocyte count and neutrophil percentage have been reported as having high sensitivity and specificity but to date the cut off values for these tests are not agreed upon. We investigated whether leukocyte count and differential of aspirated joint fluid are valuable tools in the diagnosis of suspected prosthetic joint infection. In 39 patients who underwent revision arthroplasty the cell count and differential of joint aspirates were cross-referenced with culture results and histology to confirm that these were valid tests and to determine cut off values. Cases were identified via the microbiology service of two district general hospitals: 17 patients in whom infection was identified via culture and/or histology results and 19 who were uninfected. Receiver operator characteristic curves were used to determine the correlation between the results of the two tests and to identify a suitable threshold level. For absolute leukocyte count the area under the curve was 0.997 indicating excellent agreement between the tests. A cut off value of 2000 gave a sensitivity of 100% and a specificity of 94%. Differential count had an area under the curve of 0.94. A threshold of 50% had a sensitivity of 100% and a specificity of 77%. Despite the low number of patients this study shows that the leukocyte count and differential of aspirated joint fluid are valuable tools in the diagnosis of suspected prosthetic joint infection

Aims: The diagnosis of a prosthetic joint infection is difþcult, but crucial for appropriate treatment. Scintigraphy with speciþc markers for infection (labeled white cells or immunoglobulin-G) has been reported as a more reliable diagnostic tool than clinical assessment (fever, þstula), laboratory studies [polynuclear neutrophils blood count (PNC), erythrocyte rate sedimentation (ESR), and C-reactive protein (CRP)], and preoperative aspiration. Methods: In the þrst part of this study, we retrospectively reviewed 230 patients admitted with a suspected prosthetic joint infection and compared the validity of these different diagnostic tools. 209 patients had an infection. Results: Pain, fever, ESR, and PNC are unreliable for identifying occult infection. The presence of a þstula is inconstant, but when present is very reliable to detect infection. Our study revealed sensitivity, speciþcity, positive and negative predictive value as follows: CRP: 97%, 81%, 98%, 71% respectively; aspiration: 82%, 94%, 99%, 43% respectively, and labelled scintigraphy 74%, 76%, 91%, 44% respectively. In the second part, we reviewed 23 articles which included 1,722 prosthetic joints with preoperative evaluation of infection. Conclusions: Both our study and the literature review indicate that CRP and joint aspiration are the best tools to diagnose prosthetic joint infection

Diagnosis of chronic prosthetic joint infection (PJI) is often challenging. Painful prosthesis is frequently due to an infection but to diagnose it is somethimes difficult. All recent guidelines stress the central role of joint punction in diagnosis of PJI if the infection is not demonstrated. However which test on synovial fluid must be carried out is not so clearly defined. Total white blood cell count and differential leukocite count are usually considered useful in diagnosis but cut offs reported by different studies are quite different. Moreover this test needs a relatively large amount of fluid and blood contamination of it largely affects the result. What's more the synovial fluid WBC count may be unreliable in the setting of a metal-on-metal bearing or corrosion reaction. Routine cultures should be maintained between 5 and 14 days, their sensitivity appears low in chronic infection even if witholding antimicrobial therapy before the collection of the fluid can increase the likelihood of recovery an organism. Synovial leukocyte esterase can be performed as a rapid office or intraoperative point of care test using urinalysis strips. It is cheap and easy to perform, but the presence of blood in the sample can affect the result and it needs centrifugation. Recently a new test has been proposed to detect alfa-defensine in synovial fluid. It shows a high sensitivity and an exellent specificity. We performed 25 joint punctions on 25 patients with suspected PJI (enrollment is going on). Synovial fluid collected was tested for: leukocite esterase, WBC count and differential, colture in blood colture bottle for anerobe and aerobes (BacT/ALERT Biomerieux, inc) and detection of alfa-defensine level (Synovasure – Zimmer). In patients who underwent surgery at least 5 samples of periprotesic tissue were collected for microbiologic analysis and the removed implant was sonicated according with the methodic. Furthermore samples for frozen section were sent and a histologic examination was made according to the Moriewitz – Kerr classification. The MSIS criteria was utilized to classify the case as infected or not

Aim. Data on Prosthetic joint infection (PJI) caused by multi-drug resistant (MDR) or XDR (extensively drug resistant) Gram negative bacteria (GNB) are limited. Treatment options are also restricted. We conducted a multi-national, multi-center assessment of clinical data and factors of outcome for these infections. Method. PJI were defined upon international guidelines. Data from 2000–2015 on demographics, clinical features, microbiology, surgical treatment and antimicrobial therapy was collected retrospectively. Factors associated with treatment success were evaluated by logistic regression analysis. Results. A total of 133 PJI were evaluated. Female (n=84, 61.4%) and the elderly [mean age (+/-SD) 73 (12.7)] predominated. Diabetes mellitus was the most frequent comorbidity (n=42,32.1%) followed by rheumatoid arthritis (n=14,10.7). Most PJI were early infections (84.4 %). XDR accounted for 23 cases; half of them due to Pseudomonas aeruginosa. Prevalence of MDR or XDR GNB was not different between early and late PJIs (p=0.114). Overall, P.aeruginosa (n=25, 19.1%) was followed by Klebsiella spp (n=23,17.6%) and Enterobacter spp (n=22,16.8%). PJI was located at the hip (n=85 65.6%), knee (n=41,31.3%), shoulder (n=3,2.3%) and ankle (n=1, 0.8%). Clinical characteristics included soft tissue infection (66.4%), pain (51.1%), fever (32.1%) and sinus tract(29.8%). Surgery for PJIs consisted of DAIR (debridement, antibiotics and implant retention), (n=64, 49.6%), followed by explantation of the arthroplasty (n=32, 24.8%), two-stage revision (n=16, 12,4%), one stage revision (n=9, 7%), arthrodesis (n=2, 1.6%). Median duration of antibiotic therapy was 51 days (IQR 25–75: 40–90 days). Cure after treatment was assessed in 78 patients (58.6%). No-DAIR surgical procedures in PJIs were more likely to be successful compared to DAIR surgery (75.8% vs 50%, OR 3.13, 95% CI:1.47–6.70, p=0.003)both in early or late infections. Conclusions. PJI by MDR/XDR GNB affects female, the elderly with comorbidities and previous surgery for PJI. P.aeruginosa is frequent, mostly XRD. No-DAIR procedures have higher probability of treatment success than DAIR even in early infection. Despite surgery and long-term antimicrobial administration, treatment success was less than 60%, probably reflecting the lack of effective treatment options

No single test is 100% sensitive and specific for the diagnosis of prosthetic joint infection. Joint aspiration is currently the only preoperative investigation that can establish the identity of the infecting organism and its antibiotic susceptibilities. Frequently when attempting to aspirate a joint a ‘dry tap occurs as fluid cannot be aspirated. In this situation, normal saline may be injected into the joint and then reaspirated to provide fluid for culture. The aim of this study was to ascertain the diagnostic accuracy of culture of joint aspiratie with or without saline reaspiration in the event of a dry tap. A retrospective analysis of 580 hip and knee aspirations in patients deemed to have moderate-high risk of infection and ultimately proceeded to revision arthroplasty over 12 years at a large quaternary referral centre where pre operative aspiration is routine. Fluid was aspirated in 313 (54%) cases and dry taps in which saline injection reaspiration was performed occurred in 267 (46%) cases. Overall sensitivity and specificity of diagnostic aspiration were 84% (78–89%) and 85% (81–88%) respectively. Sensitivity and specificity of saline injection-reaspiration after dry tap were 87% (79–82%) and 79% (72–84%) compared to 81% (71–88%) and 90% (85–93%) for direct aspiration. Pre operative 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 peri-operative and cement instilled antibiotic therapy. Culture of pre operative joint aspirates provides sensitive and specific diagnostic information including antimicrobial susceptibility results. Saline injection-reaspiration is a useful additional technique in those patients in whom fluid cannot be aspirated

Prosthetic joint infection (PJI) remains a devastating complication of arthroplasty. There is significant heterogeneity in treatment approaches to these infections and information on their efficacy relies on single-centre studies. This is the first multi-centre study examining current treatment approaches to patients with PJI. A retrospective cohort study was conducted over a 3-year period (January 2006 – December 2008) involving 10 hospitals in Victoria, Australia. Cases of prosthetic joint infections of hips and knees were identified using an established statewide nosocomial infection surveillance network. Individual medical records were accessed to describe the management and record the outcomes of these patients. Interim analysis from seven hospitals revealed 121 patients with PJI. Staphylococcus aureus was isolated in half of the infections with equal representation of methicillin resistant and methicillin sensitive strains. Debridement and retention (DR) was the most common treatment modality (72%), followed by resection arthroplasty without reimplantation (10%), superficial debridement and antibiotics (9%), one-stage exchange (6%) and two-stage exchange arthroplasty (3%). The timing and number of surgical interventions was however highly variable. The majority of patients underwent arthrotomy with an average of 3 debridements of the infected joint (range 0–10, standard deviation 1.7). Two-thirds of the patients with staphylococcal infections received a rifampicin-containing regimen. The course of oral antibiotic therapy was prolonged with a median duration of 132 days (interquartile range 13–357) but ranged from no oral antibiotic therapy to 1032 days. Overall 72% of patients remained infection-free after a mean follow-up of 15 months, however there was marked variation in outcomes between hospitals with success ranging from 50%-95%. This multi-centre study demonstrates that there is a wide spectrum of treatment approaches to PJI. In addition, DR is the favoured treatment modality, which differs to our European and Northern American counterparts. This study reports real-life management and outcomes from patients at several centres, including many that do not have dedicated research interest in PJI

Aim. Diagnosing or excluding a chronic prosthetic joint infection (PJI) prior to revision surgery can be a clinical challenge. To enhance accuracy of diagnosis, several biomarkers were introduced in recent years, but most are either expensive or not available as a rapid test. We compared the diagnostic accuracy of leucocyte esterase (€0.20 per sample), calprotectin (€20 per sample) and alpha defensin (€200 per sample). Method. We prospectively evaluated PJI patients with chronic pain with or without prosthetic loosening between 2017 and 2018. Synovial fluid was collected prior to revision surgery. Leucocyte esterase was measured using a reagent strip (2+ considered as positive), and calprotectin and alpha defensin were measured using a lateral flow immunoassay. Intraoperative cultures (5 periprosthetic tissue samples, synovial fluid and sonication fluid) incubated for 9 days, were used as gold standard. At least two positive cultures of low-grade microorganisms with the same antibiogram were required to diagnose PJI. Results. A total of 19 patients were included (knee =11, hip =8). None of the patients were treated with antibiotics prior to revision surgery. A PJI was diagnosed in 8 patients (42.1%). The diagnostic accuracy of leucocyte esterase vs. calprotectin vs. alpha defensin was as follows; sensitivity 50.0% vs. 87.5% vs. 87.5%, specificity 81.8% vs. 90.9% vs. 100%, positive predictive value 60.0% vs. 87.5% vs. 100% and negative predictive value 75.0% vs. 90.9% vs. 91.6%, respectively. Both calprotectin and alpha defensin were false negative in one PJI caused by Cutibacterium acnes. The other two C. acnes PJIs were correctly diagnosed with both tests. Conclusions. Calprotectin is as accurate as alpha defensin in excluding a chronic PJI at 10% of the costs. Future studies with a large number of patients are necessary to analyze its diagnostic accuracy in very low-grade infections, in particularly caused by C. acnes

Aim. The frequency of arthroplasty among older people is increasing. Taking care of Prosthetic Joint infection (PJI) in this specific population is a challenge. The purpose of this multicentric retrospective study was to evaluate the bacterial epidemiology of hip and knee PJI in octogenarians and nonagenarians over ten years. Method. Data were collected using two softwares* in each of the 4 Centers participating. Inclusion criteria:. -. age ≥ 80 years PJI (knee or hip). -. between January 2007 and December 2016. -. microbiological data available (strains isolated from osteo-articular samples). Bacterial identification: biochemical methods, followed by Malditof since 2009. For Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacteriaceae, resistance profiles to antibiotics frequently used in PJI were collected. Antimicrobial susceptibility testing: disk diffusion (recommendations: French Society of Microbiology yearly updated). Results. 413 patients were included: median age was 85 years and sex ratio was 0.6. 137 were knee PJI and 276 hip. 34% of the infections occurred < 1 month after implantation, and 49% > 6 months after implantation. Among all bacterial isolates (N=817), there was 55% of Gram positive cocci and 36% of Gram negative rods. 112 (27%) were polymicrobial infections. There was a majority of gram negative rods (41%) among isolates from polymicrobial infections. Concerning drug resistance, there was a stable proportion of ESBL among Enterobacteria (16%), whereas Methicillin resistance among S. aureus decreased from 43% in 2007 to 12% in 2016. Conclusions. An important proportion of PJI in older patients are polymicrobials, and a lot of them involve gram negative rods, almost as frequently as S. aureus. These infections are difficult to treat, and resistance of gram negative strains is one of the obstacles to overcome among these patients where surgery is not always possible. * Sirweb (I2A) and Glims (MIPS)

Aim. Prosthetic Joint Infection (PJI) remains one of the leading cause for revision arthroplasty. 1,2. Early recognition and appropriate initial treatment of early PJI with debridement, antibiotics and implant retention (DAIR) can eradicate infection on first attempt and prevent implant failure. We evaluated the outcome after one year of patients who were treated for an early PJI after primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) with DAIR. Furthermore, we determined preoperative infection markers, microbiology, and treatment factors related to treatment failure after DAIR procedure. Method. A retrospective cohort study was assembled with 91 patients undergoing DAIR after primary TKA or THP with a high suspicion of an early PJI. For all patients intraoperative cultures were obtained. Records were reviewed for demographic details, preoperative laboratory results, microbiological data, given treatment and postoperative follow-up. The primary outcome measure was infection-free implant survival at one year. Repeated DAIR was not considered as treatment failure. Results. Following DAIR in early PJI the rate of infection-free implant survival was 83% (95% confidence intervals (CI) 79 to 91) at one year follow-up, including patients with multiple DAIR procedures. Univariate analysis indicate a higher failure rate in early PJI caused by Enterococcus faecalis (p=0.04). Multivariate analysis showed that a high C-reactive protein level (CRP >100) (odds ratio 7.5, 95% CI [1.4–39.7]) and multiple debridement procedures (≥2) (p=0.004, odds ratio 8.5, 95%CI [2.1–34.3]) were independently associated with treatment failure. Conclusions. Significantly elevated preoperative serum inflammatory markers may indicate difficult-to-treat, fulminant infections. The winning team in the eradication of an early PJI on first attempt and prevent implant failure is adequate debridement and appropriate empiric antibiotics. To improve treatment success and prevent the need for multiple debridement procedures it is important to use the adequate debridement technique and to have knowledge about local bacterial resistance patterns. Inadequate use of debridement and/or antibiotics can contribute to treatment failure in early PJIs and consequently in saving the affected joint arthroplasty

Introduction. Periprosthetic infection (PJI) after primary total knee arthroplasty (TKA) remains a challenging issue affecting 1–2% of cases. Locally delivered prophylactic antibiotics, including tobramycin or gentamicin mixed in polymethylmethacrylate (PMMA) bone cement and vancomycin powder, are increasingly used despite a lack of high quality evidence for either practice. In this study, we report the antibiotic susceptibility of organisms recovered in culture from patients with acute prosthetic joint infection after primary TKA to gentamicin, tobramycin and vancomycin. Methods. Using a retrospective database of all primary TKA performed at a single institution between January, 1 2014 and July 1, 2018, we identified 18 cases of acute PJI after primary TKA, as defined by the Musculoskeletal Infection Society 2011 guidelines as less than 3 months from symptoms or index surgery to presentation. The use of antibiotic bone cement during the index procedure and time to surgical management of the infection were recorded. Fluid cultures and tissue cultures were obtained intraoperatively at the time of revision. The organisms from positive cultures underwent MIC testing to gentamicin, tobramycin and vancomycin using a gradient diffusion method (ETEST). MIC breakpoints for susceptibility were based on Clinical and Laboratory Standards Institute definitions. Results. 18 cases of PJI after TKA were identified, including 4 polymicrobial infections (22.2%) (Table 1). Average time to revision for infection was 38 days (range: 6–84 days). 34.8% of bacterial isolates were resistant to gentamicin, 39.1% were resistant to tobramycin and 17.4% were resistant to vancomycin. Of the 8 bacterial isolates resistant to gentamicin, 7 (87.5%) were susceptible tobramycin. Of the 9 bacterial isolates resistant to tobramycin, (88.9%) were susceptible to vancomycin. One bacterial isolate, a Fusobacterium nucleatum from a polymicrobial infection was resistant to gentamicin, tobramycin and vancomycin. Conclusion. Over one third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides pre-mixed in commercially available bone cements. All but one of the bacteria resistant to gentamicin and tobramycin were susceptible to vancomycin. The addition of vancomycin to bone cement or as powder in the surgical field has the potential to expand antibiotic coverage to include most organisms responsible for acute PJI after TKA. For figures, tables, or references, please contact authors directly

Aim. Prosthetic joint infections (PJI) due to Enterobacter cloacae are rare and often severe. The aim of this study is to describe cases with E. cloacae PJI. Method. We conducted a retrospective and a monocentric study in an orthopedic unit where complex bone and joint infections are managed. From 2012 to 2016, we included patients with PJI which perioperative samples were positive with E. cloacae. We collected background, clinical, biological and microbiological data of the current infection, surgical and medical treatment, and the outcome of these patients. Results. A total of twenty patients were included which 8 were male. Location was hip in 14 cases, knee in 5 cases and ankle in one case. The median time between arthroplasty and revision for infection was 3 years. Fourteen patients had at least two surgeries for previous PJI. The median time between the last surgery and the revision for E. cloacae infection was 31 days. Eleven patients were infected by extended-spectrum beta-lactamases (ESBL) strains. Most frequently, the antibiotics used were carbapenem in 9 cases, cefepim in 7 cases, a quinolone in 7 cases and fosfomycin in 4 cases. Infection was cured in 10 cases (50%) with a median time of follow-up of 24 months. Five patients had a recurrent infection, three due to Staphylococcus epidermidis, one to Staphylococcus epidermidis and Propionibacterium acnes and one to Escherichia coli. Four patients had a relapse of E. cloacae infection. One patient died from non-infectious cause (stroke). Conclusions. PJI infections due to E.cloacae usually occur early after the last prosthetic surgery, typically in patients with complex surgical history. A poor outcome, observed in nearly half of the patients could be explained in part by an association of factors: multiple risks factors, complex infectious history, a high rate of multiple resistance to antibiotics, unfavorable skin conditions

Aim. Obese patients are not only more likely to receive total joint arthroplasty, but are also more prone to postoperative complications. The most severe complication is a prosthetic joint infection (PJI), occurring two to four times more often in severely obese patients (BMI ≥ 35kg/m. 2. ) compared to non-obese patients. This higher risk for PJI may be attributed to higher glucose levels in case of diabetes mellitus, diminished wound healing or inadequate antibiotic prophylaxis. To ultimately improve the prevention measures for this specific patient category, we aimed to describe the clinical and microbiological characteristics of early acute PJI in severely obese patients. Method. We retrospectively evaluated patients with early acute PJI of the hip and knee treated with DAIR between 2006 and 2016 in three Dutch hospitals. According to protocol, cefazolin was administered as antibiotic prophylaxis during arthroplasty and adjusted to bodyweight. PJI was diagnosed using the criteria described by the Musculoskeletal Infection Society. Early acute PJI was defined as less than 21 days of symptoms and a DAIR performed within 90 days after index surgery. Several clinical and microbiological variables were collected and analyzed. Severe obesity was defined as a BMI ≥ 35kg/m. 2. . Results. A total of 356 patients were analyzed, including 73 severely obese patients (20.5%). Compared to patients with a BMI < 35kg/m. 2. , severely obese patients were relatively young (69 years vs 74 years, p=0.001), female (75.3% vs 56.9%, p=0.005), with PJI of the knee (35.6% vs 20.8%, p=0.025) and arthroplasty indicated for osteoarthritis (87.7% vs 63.3%, p=0.001). They had higher incidences of diabetes mellitus (34.2% vs 18.7%, p=0.005) and hypertension (74.0% vs 59.0%, p=0.021). Severely obese patients had more often polymicrobial infections (67.4% vs 45.7%, p=0.009) and higher rates of infection with Enterococcus species (37.0% vs 15.8%, p=0.002) and Gram-negative rods, such as Proteus species (17.4% vs 2.3%, p<0.001). This finding was most prominent in hips, comprising Gram-negative PJIs in 32.6% of severely obese patients compared to 18.1% in non-severely obese patients (p=0.030). There were no differences in the number of infections due to Staphylococcus aureus or Staphylococcus epidermidis. Conclusions. Our results demonstrate that severely obese patients with early acute PJI have higher rates of polymicrobial infections with involvement of Gram-negative rods and enterococci, especially in the hip region. Our data stress the importance of improving preventive strategies in this specific patient category, which may entail extension of antibiotic prophylaxis to a broader Gram-negative and Gram-positive coverage

In a new rabbit model of carbapenem-resistant Klebsiella pneumoniae knee-prosthesis infection, we studied the efficacy of colistin cement alone or in combination with systemic intramuscular (i.m.) injections of colistin. Seven days after infection, surgical debridement and removal of the infected prostheses were performed, and rabbits were randomly assigned to one of four different treatment groups of twelve rabbits: prosthesis replacement by drug-free cement spacer (control) prosthesis replacement by colistin-loaded cement spacer (3 MUI of colistin/40 g of cement) (colistin local), prosthesis replacement by drug-free cement spacer and i.m. colistin (12 mg/kg of body weight, three time a day for 7 days), or colistin local + i.m. We observed a statistically significant difference (p = 0.049) between the colistin local + systemic group and the control group in the criteria of number of rabbits with sterile bone under the total number of rabbits. Combination of systemic and local colistin could be an interesting therapeutic option to cure carbapenem-resistant Klebsiella pneumoniae peri prosthetic joint infection

The benefits of cell salvage autotransfusion are well reported. There is a common non-evidenced belief amongst revision arthroplasty surgeons that auto-transfusion is potentially contraindicated in infected revisions.

The aim is to study the immediate and delayed outcomes of using cell saver on patients undergoing PJI surgery.

Prospective cohort service evaluation registered with the local audit department. 20 PJI cases in 18 patients where cell saver was used over a period of 4 years. Intraoperative fluid and tissue samples were taken for culture. Blood culture from salvaged blood pre and post leucodepletion filter were sent for microbiological analysis. Data on type of surgery, blood loss, further allogenic transfusion and SIRS response was collected. Success of infection clearance was assessed using 2019 MSIS ORT. Five patients receiving autologous blood in non-infection cases were used as controls.

Mean age for the PJI group was 67.7 years, 67% female. 11 patients (67%) had 1st stage surgery and 5 (25%) underwent 2nd stage whereas 4 patients had single stage surgery. The mean calculated blood loss was 1398 mls (range 400–3000mls). 6 Patients required further allogenic transfusion. 16 patients received blood via a leuco-depletion filter. The same organism grown from tissues was identified in post-filter blood in 8/17 patients (47%).

2/20 have grown a different organism in post-filtered blood, _P.Acne._

2 patients developed SIRS upon auto-transfusion, however one was thought to be secondary to cementing. The control group had 443 mls mean amount of blood loss and 1 patient developed a SIRS response.

14/20 (70%) patients had successful clearance of infection (tier 1) 2 patients died prior to undergoing 2nd stage.

Using cell saver did not impact main outcome of infection clearance in PJI surgery. We would advocate its routine usage whilst avoiding direct collection of heavily contaminated blood.

Introduction: Infections associated with prosthetic joints cause significant morbidity and account for substantial costs for health care systems. The management of prosthetic joint infections is less standardized, because of the variable clinical presentations and the lack of data from randomized, controlled trials. We evaluated the results of surgical one stage versus two stage exchange of patients diagnosed positive for prosthetic infection following total hip replacement in correlation with a classification described by Mc Pherson. Material and Methods: 94 patients were diagnosed positive for prosthetic joint infection following total hip replacement in the years 1995 to 2004: gender distribution was 45 male and 49 female patients. 37 patients were treated with a one stage exchange, 57 patients underwent a two step procedure. Patients were further divided into two groups following the mentioned classification described by Mc Pherson as infection type I+II and III. Further characterisation was performed following systemic host grade (A versus B+C) and local extremity grade 1 versus 2+3. Results: Eradication of prosthetic infection was achieved in 94, 5% (n=52) within the group of two stage exchange and 56, 8% (n=21) of patients treated with a one stage procedure. Outcome of patients following a one stage or a two step exchange was overall significantly different with p< .001. Further deviations between the described two procedures were noted in the subgroups following the classification described by Mc Pherson. A benefit of patients who underwent a two step procedure was seen according the severity of the classification following Mc Pherson. Conclusion: Eradication rate of prosthetic joint infections differs statistically significant overall and in the subgroups following Mc Pherson in dependence of the surgical procedure. For this reason the individual surgical procedure should be geared to an algorithm, following the classification described by Mc Pherson

The Danish Hip Arthroplasty Register (DHR) is a national database on total hip arthroplasties (THAs) with a high completeness and validity of registration for primary procedures. The aim was to validate the registration in DHR for revisions due to Prosthetic Joint Infection (PJI). We identified a cohort of patients in the DHR who underwent primary THA from January 1, 2005 to December 31, 2012 and we followed these patients until first-time revision, death, emigration or December 31, 2012. The PJI diagnosis registered was tested against a gold standard encompassing information from microbiology, prescription, and clinical biochemistry registries in combination with clinical findings retrieved from medical records. We estimated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% confidence interval (CI) for PJI in DHR alone and in DHR combined with microbiology registries. Out of 37,828 primary THAs, 1,382 were registered with any revision, 232 of which were due to PJI. For PJI revisions in DHR, the sensitivity was 67.0% (CI: 61.0 – 72.6), specificity 95.2% (CI: 93.8 – 96.4), PPV 77.2% (CI: 71.2 – 82.4), and NPV 92.3% (CI 90.7 – 93.8). Combining DHR with microbiology registries led to a notable increased in the sensitivity for PJI revision to 90.3% (CI: 86.1 – 93.5) and likewise for specificity 99.6% (CI: 99.1 – 99.9), PPV 98.4% (CI: 95.9 – 99.6) and NPV 98.5% (CI: 97.6 – 99.1). Only two thirds of PJI revisions were captured in DHR and the PPV was moderate. However, combining DHR with microbiology registries improved the accuracy remarkably. The study was supported by Region of Southern Denmark and Lillebaelt Hospitals

Aim. Over the past three years, roughly 100,000 hip and knee replacements have been performed by the Brazilian Public Healthcare System. Prosthetic joint infection (PJI) is expected to range between 1% to 10% after primary and revisions joint arthroplasties, respectively. So far, there have been no published national PJI data which would be helpful at developing local preventive strategies and guide surgeons and clinicians. We aimed at describing the epidemiological, clinical and microbiological PJI results of a national and collaboration study among infectious diseases specialists and orthopaedic surgeons, including academic, public and private institutions. Method. We prospectively enrolled patients with PJI in a national cohort study among 12 hospitals from 6 different States to describe host, pathogens, diagnosis, surgery strategies adopted (according to the standard hospital-based guideline) and outcome after 1- and 2-years follow-up. PJI was defined using the IDSA criteria (Osmon D, et al. Clin Infect Dis. 2013). Patients were enrolled from July 2013 to December 2015. Results. Overall, 234 patients undergoing hip, knee and shoulder (n=3) arthroplasty were eligible; 35 were excluded: did not fulfil the inclusion criteria (n=14), withdrawal informed consent (n=11) and early lost to follow-up (n=10). A total of 199 were available for analysis. Twenty-two (11%) patients died during the follow-up, most of which (95%) occurred within 1 year of PJI diagnosis. In the one-year (12 patients lost to follow-up) and two-year (18 patients lost to follow-up) post-diagnosis analysis, overall treatment failure occurred in 13.3% (n=22/166), and 17% (n=25/147). Knee and hip rate failure in the 1- and 2-year follow up were 12.2% (n=9/74), 15.4% (n=14/91), and 16.2% (n=11/68), 18.2% (n=14/77), respectively. Debridement with implant retention (DAIR), one-stage exchange, two-stage exchange, and arthrodesis was performed in 44.7%, 25.4%, 22.3%, 7.6% respectively. Failure rates for DAIR, one-stage exchange, two-stage exchange, and arthrodesis after 1- and 2-year follow-up were 24.2% (n=16/66), 4.3% (n=2/46), 9.8% (4/41), 0% (n=0/15), and 28.6% (n=16/56), 4.8% (n=2/42), 15.8% (n=6/38), 0% (n=0/15), respectively. Microbial diagnosis yielded positive culture in 71.7%. Staphylococcus aureus (34%), coagulase-negative staphylococci (28%), Pseudomonas aeruginosa (17%) were more prevalent. Polymicrobial PJI were diagnosed in 32.8%. Conclusions. This is so far the largest Brazilian cohort of patients with PJI showing an overall 2-years failure-free survival rate of 83%, in which DAIR is the most frequent and less successful strategy, single-stage exchange seems to be a growing surgical option. Polymicrobial and non-fermenting Gram-negative bacilli and Enterobacteriacae is frequent

Aim. When a prosthetic joint infection (PJI) is suspected, guidelines recommend performing periprosthetic samples, at least one for histopathological examination and 3 to 6 for microbiological culture. The diagnosis of infection is based on the presence of neutrophil granulocytes whose number and morphology can be variable, resulting in definition of “acute” inflammation. The acute inflammation of periprosthetic tissue is supportive of infection. Since 2007, in our hospital, for all patients with suspected PJI who underwent surgery, from each sample taken by the surgeon, one part has been sent to the pathologist and the other one to the microbiologist. Our aim was to compare histopathological to microbiological results from samples taken intraoperatively at the same site. Method. We conducted a retrospective study including all surgeries for which at least one couple “histopathology-culture” was found. Exclusion criterion was a history of antimicrobial treatment 2 weeks prior the surgery. Results. From July 2007 to April 2015, 309 surgeries for suspected PJI were performed in 181 patients. Median age of the study population was 70 years, 60% of patients were male, 45% had a history of joint infection. The location of arthroplasty was knee in 50% of cases and hip in 46%, ankle and shoulder in 4%. Surgery was performed within one month after the last prosthetic surgery in 15% of cases. According to the criteria from the Musculoskeletal Infection Society, 60% of cases should have been considered as having an infection. The median number of samples per surgery was 4 (IQR 3–5) for histopathological examination and 5 (IQR 4–6) for culture. Finally, 1247 couples “histopathology-culture” were available. Among them, histopathological examination showed acute inflammation in 292 cases (23%) and subacute inflammation in 327 cases (26%). Microorganisms considered to be pathogenic were found in 582 samples (47%). The presence of neutrophil granulocytes was well correlated with the presence of those microorganisms (OR=4.1; IC 95% 3.1–5.5). As expected, the highest correlation between acute inflammation and positive culture was observed for early infection (< 1 month) (OR = 9; 3.6–23.4) and Staphylococcus aureus infection (OR = 4.8; 3.3–7.0). There was no correlation between acute or low-grade inflammation and anaerobic or Candida infection. Conclusions. Our results confirmed histopathological examination is better correlated with culture in acute infection and/or infection due to highly virulent bacteria but must be interpreted with caution in case of chronic infection or infections due to microorganisms with low virulence

Surgical treatment of Hip PJI by resection of the infected implants and tissue and placement of a “spacer” which elutes antibiotic via antibiotic loaded cement is an accepted treatment option. There is some controversy over whether this “spacer” should be articulating or static. Proponents of the articulating option argue that there is improved function and maintenance of the soft tissue envelop. Critics have suggested that additional biomaterials may compromise eradication of infection. This study compares our results of the 2 treatment options.

A review of our institutional PJI database between 2016 and 2021 identified 87 patients who were treated with resection arthroplasty for unilateral total hip PJI. The cohort was analyzed for demographics and type for surgery, as well as medical comorbidities, survivorship, and treatment success.

44 patients were female, the mean age of all patients was 62. 44 patients were treated with Articulating apacers, and 43 patients treated with static spacers. There was no significant difference between ASA or Elixhauser score, and no significant difference between mortality or treatment failure.

This study did not show any difference between the patients who receive static spacers, from those who received articulating spacers, and deomstrated similar treatment success rates. From this data there does not appear to be any difference in success rates between those patients that were treated with static spacers and those that were treated with articulating spacers.

Post operative prosthetic joint infection (PJI) is the most common cause of failure of total joint arthroplasty, requiring revision surgery, but a gold standard for the diagnosis and the treatment of PIJ is still lacking [1]. SuPAR, the soluble urokinase plasminogen activation receptor, has been recently described as a powerful diagnostic and prognostic tool, able not only to detect sepsis but also to discriminate different grade of sepsis severity [2,3]. This study aimed to examine the diagnostic value of SuPAR in post operative PJI, in order to explore the possible application of this new biomarker in the early diagnosis of PJI. The level of SuPAR have been measured in PJI patients and controls (patients undergoing prosthesis revision without infection), and correlated with pro and anti inflammatory markers (CRP C-reactive protein, IL-6, IL-1 TNFα, IL-10, IL-12, IL-8, IL1ra and the chemokine CCL2). Statistical analysis of Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) was performed. As described in Figure 1, serum SuPAR displayed a strongly significative increase in PJI patients compared to not infected controls, and a significative positive correlation with C-reactive protein, IL-6, IL-1 and TNFα and the chemokine CCL2. SuPAR displayed a very good AUC, significantly higher than CRP and IL-6 AUC. This study clearly show that the measure of Serum level of SuPAR provide a extremely important benefit because it is a precise indicator of bacterial infection, and the addition of SuPAR serum level measurement to classical inflammatory markers can strongly improve the diagnosis of prosthesis joint infection. The authors acknowledge ViroGates, Denmark for providing suPARNOSTIC Standard Kit. The authors would also acknowledge the Italian Ministero dell’ Istruzione, Università e Ricerca (MIUR) and Italian Ministero della Salute for providing funds for this research project

Introduction. Pre-operative aspiration and culture is the gold standard for the diagnosis of peri-prosthetic infection. This study aimed to ascertain the diagnostic accuracy of culture of joint aspiration with or without saline re-aspiration in the event of a dry-tap. Patients/Materials & Methods. Retrospective analysis of 343 hip aspirations in patients deemed to have moderate-high risk of infection and ultimately proceeded to revision arthroplasty over 12 years at a large quaternary referral centre where pre-operative aspiration is routine. Results. Fluid was aspirated in 141(41%) cases and dry taps in which saline injection-re-aspiration was performed occurred in 202 (59%) cases. Overall sensitivity and specificity of diagnostic aspirate were 82% (74–88%) and 79% (74–84%) respectively. Sensitivity and specificity of saline injection-re-aspiration after dry tap were 79% (64–87%) and 86% (78–92%) compared to 84% (74–91%) and 74% (66–81%) for direct aspiration. Discussion. Pre-operative 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-re-aspiration 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 peri-operative and cement instilled antibiotic therapy. Conclusions. Culture of pre-operative joint aspirates provides sensitive and specific diagnostic information, including antimicrobial susceptibility results. Saline injection-re-aspiration is a useful additional technique in those patients in whom fluid cannot be aspirated

Periprosthetic joint infection (PJI) occurs in 0.2-2% of primary hip and knee arthroplasty and is a leading cause of revision surgery, impaired function, and increased morbidity and mortality. Topical, intrawound vancomycin administration allows for high local drug concentrations at the surgical site and has demonstrated good results in prevention of surgical site infection after spinal surgery. It is a promising treatment to prevent infection following hip and knee arthroplasty. Prior studies have been limited by small sample sizes and the low incidence of PJI. This systematic review and meta-analysis was performed to determine the effectiveness of topical vancomycin for the primary prevention of PJI in hip and knee arthroplasty.

A search of Embase, MEDLINE, and PubMed databases as of June 2020 was performed according to PRISMA guidelines. Studies comparing topical vancomycin to standard perioperative intravenous antibiotics in primary THA and TKA with a minimum of three months follow-up were identified. The results from applicable studies were meta-analysed to determine the impact of topical vancomycin on PJI rates as well as wound-related and overall complications. Results were expressed as odds ratios (ORs) and 95% confidence intervals

Nine comparative observational studies were eligible for inclusion. 3371 patients treated with 0.5-2g of topical vancomycin were compared to 2884 patients treated with standard care. Only one of nine studies found a significantly lower rate of PJI after primary THA or TKA (OR 0.09-1.97, p=0.04 for one study, p>0.05 for eight of nine studies), though meta-analysis showed a significant benefit, with vancomycin lowering PJI rates from 1.6% in controls to 0.7% in the experimental group (OR 0.47, p=0.02, Figure 1). Individually, only one of five studies showed a significant benefit to topical vancomycin in THA, while none of seven studies investigating PJI after TKA showed a benefit to topical vancomycin. In meta-analysis of our subgroups, there was a significant reduction in PJI with vancomycin in THA (OR 0.34, p=0.04), but there was no significant difference in PJI after TKA (OR 0.60, p = 0.13). In six studies which reported complication rates other than PJI, there were no significant differences in overall complication rates with vancomycin administration for any study individually (OR 0.48-0.94, p>0.05 for all studies), but meta-analysis found a significant difference in complications, with a 6.7% overall complication rate in controls compared to 4.8% after topical vancomycin, largely driven by a lower PJI incidence (OR 0.76, p=0.04).

Topical vancomycin is protective against PJI after hip and knee arthroplasty. No increase in wound-related or overall complication rates was found with topical vancomycin. This meta-analysis is the largest to date and includes multiple recent comparative studies while excluding other confounding interventions (such as povidone-iodine irrigation). However, included studies were predominantly retrospective and no randomized-controlled trials have been published. The limited evidence summarized here indicates topical vancomycin may be a promising modality to decrease PJI, but there is insufficient evidence to conclusively show a decrease in PJI or to demonstrate safety. A prospective, randomized-controlled trial is ongoing to better answer this question.

For any figures or tables, please contact the authors directly.

Tc 99m labelled leukocytes scintigraphy (LLS) could be useful for the diagnosis of bone and joint infections. The aim of our study was to evaluate its performances specifically in the diagnosis of prosthetic joint infection (PJI). We conducted a multicenter -7 year- retrospective study including 164 patients with suspected PJI who underwent surgical treatment. In each case, 5 intraoperative samples were taken. Diagnosis of infection was confirmed if two or more samples yielded the same microbial agent. LLS was considered as « positive » if an accumulation of leukocytes was observed in early stage and increased in late stage (24 hours). Among these patients, 123 had also a bone scintigraphy. A total of 168 PJ were analyzed: 150 by in vitro polymorphonuclear labelled leukocytes scintigraphy (PLLS) and 18 by anti-granulocytes antibodies labelled leukocytes scintigraphy (LeukoScan®). Location of PJ were: hip (n = 63), knee (n = 71), miscellaneous (n = 4). According to microbiological criteria 62 hip prosthesis and 48 knee prosthesis were considered as infected. Sensitivity (Se), Specificity (Sp), Positive Predictive Value (PPV) and Negative Predictive Value of PLLS were: 72%, 60%, 80% and 47%. Se of LLS was higher for knee PJI (87%) than for hip PJI (57%) [p = 0.002]. Although Sp was higher for hip PJI (75%) than for knee PJI (52%) [p = 0.002]. The lowest Se was found for coagulase negative staphylococci (70%) and the highest for streptococci (87.5%). However the difference of Se between bacteria was not significant. Regarding bone scintigraphy, Se, Sp, PPV and NPV were: 94%, 11%, 65% and 50%. In our study, performances of LLS were rather low and varied according to the location of infection. Differences of LLS Se between bacteria was not significant. Bone scintigraphy has a high Se but lacks Sp