Aims. It remains difficult to diagnose early postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). We aimed to validate the optimal cutoff values of ESR, CRP, and synovial fluid analysis for detecting early postoperative PJI in a large series of primary TKAs. Methods. We retrospectively identified 27,066 primary TKAs performed between 2000 and 2019. Within 12 weeks, 169 patients (170 TKAs) had an aspiration. The patients were divided into two groups: those evaluated ≤ six weeks, or between six and 12 weeks postoperatively. The 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI diagnosis in 22 TKAs. The mean follow-up was five years (two months to 17 years). The results were compared using medians and Mann-Whitney U tests and thresholds were analyzed using receiver operator characteristic curves. Results. Within six weeks, the median CRP (101 mg/l vs 35 mg/l; p = 0.011), synovial WBCs (58,295 cells/μl vs 2,121 cells/μl; p ≤ 0.001), percentage of synovial neutrophils (91% vs 71% (p < 0.001), and absolute synovial neutrophil count (ANC) (50,748 cells/μl vs 1,386 cells/μl (p < 0.001) were significantly higher in infected TKAs. Between six and 12 weeks, the median CRP (85 mg/l vs 5 mg/l (p < 0.001)), ESR (33 mm/hr vs 14 mm/hr (p = 0.015)), synovial WBCs (62,247 cells/μl vs 620 cells/μl (p < 0.001)), percentage of synovial neutrophils (93% vs 54% (p < 0.001)), and ANC (55,911 cells/μl vs 326 cells/μl (p < 0.001)) were also significantly higher in infected TKAs. Optimal thresholds at ≤ six weeks were: CRP ≥ 82 mg/l (sensitivity 70%, specificity 77%), synovial WBCs ≥ 8,676 cells/μl (83%, 90%), percentage of synovial neutrophils ≥ 88% (67%, 78%), and ANC ≥ 8,346 cells/μl (83%, 91%). Between six and 12 weeks, thresholds were: CRP ≥ 34 mg/l (90%, 93%), synovial WBCs ≥ 1,983 cells/μl (80%, 85%), percentage of synovial neutrophils ≥ 76% (80%, 81%), and ANC ≥ 1,684 cells/μl (80%, 87%). Conclusion. Early PJI after TKA should be suspected within six weeks if the CRP is ≥ 82 mg/l, synovial WBCs are ≥ 8,676 cells/μl, the percentage of synovial neutrophils is ≥ 88%, and/or the ANC is ≥ 8,346 cells/μl. Between six and 12 weeks, thresholds include a CRP of ≥ 34 mg/l, synovial WBC of ≥ 1,983 cells/μl, a percentage of synovial neutrophils of ≥ 76%, and/or an ANC of ≥ 1,684 cells/μl. Cite this article: Bone Joint J 2021;103-B(6 Supple A):177–184

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

Aims. The diagnosis of periprosthetic joint infection (PJI) continues to present a significant clinical challenge. New biomarkers have been proposed to support clinical decision-making; among them, synovial fluid alpha-defensin has gained interest. Current research methodology suggests reference methods are needed to establish solid evidence for use of the test. This prospective study aims to evaluate the diagnostic accuracy of high-performance liquid chromatography coupled with the mass spectrometry (LC-MS) method to detect alpha-defensin in synovial fluid. Methods. Between October 2017 and September 2019, we collected synovial fluid samples from patients scheduled to undergo revision surgery for painful total knee arthroplasty (TKA). The International Consensus Meeting criteria were used to classify 33 PJIs and 92 aseptic joints. LC-MS assay was performed to measure alpha-defensin in synovial fluid of all included patients. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) were calculated to define the test diagnostic accuracy. Results. The AUC was 0.99 (95% confidence interval (CI) 0.98 to 1.00). Receiver operating characteristic (ROC) analysis showed that the optimal cut-off value of synovial fluid alpha-defensin was 1.0 μg/l. The sensitivity of alpha-defensin was 100% (95% CI 96 to 100), the specificity was 97% (95% CI 90 to 98), the positive predictive value was 89.2% (95% CI 82 to 94), and negative predictive value was 100% (95% CI 96 to 100). ROC analysis demonstrated an AUC of 0.99 (95% CI 0.98 to 1.0). Conclusion. The present study confirms the utility of alpha-defensin in the synovial fluid in patients with painful TKA to select cases of PJI. Since LC-MS is still a time-consuming technology and is available in highly specialized laboratories, further translational research studies are needed to take this evidence into routine procedures and promote a new diagnostic approach. Cite this article: Bone Joint J 2022;104-B(9):1047–1051

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

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

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

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

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

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

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

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

Introduction. Recent focus has queried whether of deoxyribonucleic acid (DNA) sequencing modalities of bacterial DNA found in periarticular fluid and tissues will improve in periprosthetic joint infection (PJI) diagnosis and organism identification diagnostic accuracy for periprosthetic joint infection The purpose of this study was to compare the diagnostic accuracy of next generation sequencing (NGS) to polymerase chain reaction (PCR) multiplex, and culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al. [1] in the diagnosis of periprosthetic knee infections. Methods. In this retrospective study, aspirate or tissue samples were collected in 70 revision and 58 primary knee arthroplasties for routine diagnostic workup for PJI and sent to the laboratory for NGS and PCR multiplex. Concordance along with statistical differences between diagnostic studies were calculated using Chi-squared test for categorical data. Results. When comparing to the MSIS criteria, concordance was 78.1% for NGS, 66.4% for PCR, and 85.9% for culture (p<0.001). There was no significant difference based on prior infection (p=0.825), or sample collection method (tissue swab or synovial fluid) (p=0.986). Fifteen samples were culture positive and NGS negative, of which 10 (66.7%) met both criteria for PJI. Thirteen patients were culture negative but NGS positive, of which 2 (15.4%) met both criteria. Concordance was 100% between the MSIS criteria and criteria proposed by Parvizi et al. [1]. Conclusion. In this initial cohort NGS was more accurate than 16s subunit PCR techniques, but less accurate than culture in the diagnosis of PJI determining the presence or absence of PJI. What is not clear is how NGS will perform against culture in terms of identifying the specific bacterial strain. Currently, laboratory tests used for either criteria for PJI diagnosis should be obtained regardless of NGS along with the overall clinical picture to help guide decision making for PJI treatment. For figures, tables, or references, please contact authors directly

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

Aims. To describe the risk of periprosthetic joint infection (PJI) and reoperation in patients who have an acute, traumatic wound dehiscence following total knee arthroplasty (TKA). Methods. From January 2002 to December 2018, 16,134 primary TKAs were performed at a single institution. A total of 26 patients (0.1%) had a traumatic wound dehiscence within the first 30 days. Mean age was 68 years (44 to 87), 38% (n = 10) were female, and mean BMI was 34 kg/m. 2. (23 to 48). Median time to dehiscence was 13 days (interquartile range (IQR) 4 to 15). The dehiscence resulted from a fall in 22 patients and sudden flexion after staple removal in four. The arthrotomy was also disrupted in 58% (n = 15), including a complete extensor mechanism disruption in four knees. An irrigation and debridement with component retention (IDCR) was performed within 48 hours in 19 of 26 knees and two-thirds were discharged on antibiotic therapy. The mean follow-up was six years (2 to 15). The association of wound dehiscence and the risk of developing a PJI was analyzed. Results. Patients who sustained a traumatic wound dehiscence had a 6.5-fold increase in the risk of PJI (95% confidence interval (CI) 1.6 to 26.2; p = 0.008). With the small number of PJIs, no variables were found to be significant risk factors. However, there were no PJIs in any of the patients who were treated with IDCR and a course of antibiotics. Three knees required reoperation including one two-stage exchange for PJI, one repeat IDCR for PJI, and one revision for aseptic loosening of the tibial component. Conclusion. Despite having a traumatic wound dehiscence, the risk of PJI was low, but much higher than experienced in all other TKAs during the same period. We recommend urgent IDCR and a course of postoperative antibiotics to decrease the risk of PJI. A traumatic wound dehiscence increases risk of PJI by 6.5-fold. Cite this article: Bone Joint J 2021;103-B(6 Supple A):191–195

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

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

Aims. Infection complicating primary total knee arthroplasty (TKA) is a common reason for revision surgery, hospital readmission, patient morbidity, and mortality. Increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) is a particular concern. The use of vancomycin as prophylactic agent alone or in combination with cephalosporin has not demonstrated lower periprosthetic joint infection (PJI) rates, partly due to timing and dosing of intravenous (IV) vancomycin administration, which have proven important factors in effectiveness. This is a retrospective review of a consecutive series of primary TKAs examining incidence of PJI, adverse reactions, and complications using IV versus intraosseous (IO) vancomycin at 30-day, 90-day, and one-year follow-up. Methods. A retrospective review of 1,060 patients who underwent TKA between May 2016 to July 2020 was performed. There were 572 patients in the IV group and 488 in the IO group, with minimal 30 days of follow-up. Patients were followed up at regularly scheduled intervals (two, six, and 12 weeks). No differences between groups for age, sex, BMI, or baseline comorbidities existed. The IV group received an IV dose of 15 mg/kg vancomycin given over an hour preceding skin incision. The IO group received a 500 mg dose of vancomycin mixed in 150 ml of normal saline, injected into proximal tibia after tourniquet inflation, before skin incision. All patients received an additional dose of first generation cephalosporin. Evaluation included preoperative and postoperative serum creatinine values, tourniquet time, and adverse reactions attributable to vancomycin. Results. Incidence of PJI with minimum 90-day follow-up was 1.4% (eight knees) in the IV group and 0.22% (one knee) in IO group (p = 0.047). This preliminary report demonstrated an reduction in the incidence of infection in TKA using IO vancomycin combined with a first-generation cephalosporin. While the study suffers from limitations of a retrospective, multi-surgeon investigation, early findings are encouraging. Conclusion. IO delivery of vancomycin after tourniquet inflation is a safe and effective alternative to IV administration, eliminating the logistical challenges of timely dosing. Cite this article: Bone Joint J 2021;103-B(6 Supple A):13–17

Introduction. Extraction of implants due to periprosthetic infection (PJI) following complex revision total knee arthroplasty (rTKA) with extensive hardware can be a daunting undertaking for surgeon and patient alike. We question whether irrigation and debridement (I&D) has a role in this difficult situation with respect to infection control, reoperation, and function. Methods. rTKAs for PJI from 2005–2016 were reviewed. Extensive hardware was defined as: metaphyseal cone/sleeve fixation, distal femoral replacement, periprosthetic fracture hardware, or stems >75mm. Cases were categorized by treatment (I&D or 2-stage exchange). Results. 87 patients were identified with extensive hardware and PJI − 63 I&Ds and 42 2-stages. Follow-up was 3.7 years. Success defined as no re-operation for infection was similar − 38/63 (60.3%) I&D vs 28/42 (66.7%) 2-stage (p=0.54). 26/42 (61.9%) 2-stages required static spacers for post-extraction bone loss or wound problems. Only 14/42 (33%) 2-stages were successfully replanted without re-infection. 11/42 (26.1%) 2-stages had retained spacers while 7/42 (16.7%) 2-stages were eventually fused. In contrast, 38/63 (60.3%) I&Ds maintained original implants without further surgery. 8/63 (12.7%) required repeat I&D; 9/63 (14.3%) underwent eventual 2-stage. Chronic antibiotic suppression was utilized in 53/63 (84.1%) I&Ds and 17/42 (40.5%) 2-stages (p<0.001). Amputation rates were similar − 9/63 (14.3%) I&D vs 7/42 (16.7%) 2-stage (p=0.79). Ambulatory rates were similar − 46/63 (73.0%) I&D vs 24/42 (57.1%) 2-stage (p=0.09). More patients who underwent I&D had a functional TKA at final follow-up (53/63 (84.1%) I&D vs 20/42 (47.6%) 2-stage; p<0.001). Mortality was high − 22/59 (37.3%) I&D vs 13/37 (35.1%) 2-stage (p=1.00). Conclusion. In the setting of PJI following rTKA with extensive hardware, morbidity and mortality is high. I&D with chronic suppression appears as effective as 2-stage procedures in preventing reoperation for infection and maintaining ambulatory status while avoiding the morbidity of 2-stage exchange

Introduction. Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty. Patients undergoing revision for PJI may experience considerable psychological distress and symptoms of depression, both of which are linked to poor post-operative outcomes. We therefore aim to identify the prevalence of depressive symptoms in patients prior to treatment for PJI. Methods. All patients between September 2008 – October 2018 undergoing single or 2-stage revision for PJI with minimum 1-year follow-up were retrospectively reviewed at a single institution. The 2-stage (n=37) and single stage (n=39) patients that met inclusion criteria were matched based off age (+/−5), gender and BMI (+/−5) to patients undergoing aseptic revisions. Based on prior literature, patients were considered to have depressive symptoms if their VR-12 mental component score (MCS) was below 42. Using Student's t-tests, outcomes evaluated included pre-operative and 1-year post-operative VR-12 MCS and physical component scores (PCS). Results. Compared to matched controls, there was a significant difference in pre-operative depressive symptoms in patients undergoing 2-stage revision (40.5% vs 10.8%, p = 0.003) but not 1 year post-operatively (21.6% vs 10.8%, p = 0.2). Among single stage patients, there was no difference pre-operatively (20.5% vs 12.8%, p = 0.36) or 1 year post-operatively (15.3% vs 15.3%, p=1.0). PCS were significantly lower in 2-stage patients pre-operatively (31.6 vs 36.0, p=0.05) but not post-operatively (40.0 vs 39.7, p=0.89). In single stage patients there was no difference in PCS both pre-operatively (34.8 vs 34.0, p=0.78) or post-operatively (38.6 vs 39.4, p=0.79). Conclusion. In addition to lower pre-operative function, patients undergoing 2-stage revision for PJI have a four times higher prevalence of pre-operative depressive symptoms compared to patients undergoing aseptic revision. Orthopedic surgeon awareness and screening of 2-stage patients pre-operatively with referral for potential treatment of depression if needed may help improve early outcomes post-operatively

Introduction. Next generation sequencing (NGS) has been shown to facilitate detection of microbes in a clinical sample, particularly in the setting of culture-negative periprosthetic joint infection (PJI). However, it is unknown whether every microbial DNA signal detected by NGS is clinically relevant. This multi-institutional study was conceived to 1) identify species detected by NGS that may predict PJI, then 2) build a predictive model for PJI in a developmental cohort; and 3) validate the predictive utility of the model in a separate multi-institutional cohort. Methods. This multicenter investigation involving 15 academic institutions prospectively collected samples from 194 revision total knee arthroplasties (TKA) and 184 revision hip arthroplasties (THA) between 2017–2019. Patients undergoing reimplantation or spacer exchange procedures were excluded. Synovial fluid, deep tissue and swabs were obtained at the time of surgery and shipped to MicrogenDx (Lubbock, TX) for NGS analysis. Deep tissue specimens were also sent to the institutional labs for culture. All patients were classified per the 2018 Consensus definition of PJI. Microbial DNA analysis of community similarities (ANCOM) was used to identify 17 candidate bacterial species out of 294 (W-value >50) for differentiating infected vs. noninfected cases. Logistic Regression with LASSO model selection and random forest algorithms were then used to build a model for predicting PJI. For this analysis, ICM classification was the response variable (gold standard) and the species identified through ANCOM were the predictor variables. Recruited cases were randomly split in half, with one half designated as the training set, and the other half as the validation set. Using the training set, a model for PJI diagnosis was generated. The optimal resulting model was then tested for prediction ability with the validation set. The entire model-building procedure and validation was iterated 1000 times. From the model set, distributions of overall assignment rate, specificity, sensitivity, positive predictive value (PPV) and negative predicative value (NPV) were assessed. Results. The overall predictive accuracy achieved in the model was 75.9% (Figure 1). There was a high accuracy in true-negative and false-negative classification of patients using this predictive model (Figure 2), which has previously been a criticism of NGS interpretation and reporting. Specificity was 97.1%, PPV was 75.0%, and NPV was 76.2%. On comparison of the distribution of abundances between ICM-positive and ICM-negative patients, Staphylococcus aureus was the strongest contributor (F=0.99) to the predictive power of the model (Figure 3). In contrast, Cutibacterium acnes was less predictive (F=0.309) and noted to be abundant across both infected and noninfected revision TJA samples. Discussion. This study is the first to utilize predictive modeling algorithms on a large prospective multicenter database in order to transform analytic NGS data into a clinically relevant diagnostic signal. Our collaborative findings suggest the microbial DNA signal identified on NGS may be an independent useful adjunct for the diagnosis of PJI, as well as help identify causative organisms. Further work applying artificial intelligence tools will improve accuracy, predictive power and clinical utility of high-throughput sequencing technology. For figures, tables, or references, please contact authors directly