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

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

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date. Cite this article: Bone Joint J 2023;105-B(11):1135–1139

Knee arthrodesis is a potential salvage procedure for limb preservation after failure of total knee arthroplasty (TKA) due to infection. In this study, we evaluated the outcome of single-stage knee arthrodesis using an intramedullary cemented coupled nail without bone-on-bone fusion after failed and infected TKA with extensor mechanism deficiency. Between 2002 and 2012, 27 patients (ten female, 17 male; mean age 68.8 years; 52 to 87) were treated with septic single-stage exchange. Mean follow-up duration was 67.1months (24 to 143, n = 27) (minimum follow-up 24 months) and for patients with a minimum follow-up of five years 104.9 (65 to 143,; n = 13). A subjective patient evaluation (Short Form (SF)-36) was obtained, in addition to the Visual Analogue Scale (VAS). The mean VAS score was 1.44 (SD 1.48). At final follow-up, four patients had recurrent infections after arthrodesis (14.8%). Of these, three patients were treated with a one-stage arthrodesis nail exchange; one of the three patients had an aseptic loosening with a third single-stage exchange, and one patient underwent knee amputation for uncontrolled sepsis at 108 months. All patients, including the amputee, indicated that they would choose arthrodesis again. Data indicate that a single-stage knee arthrodesis offers an acceptable salvage procedure after failed and infected TKA.

Cite this article: Bone Joint J 2015;97-B:649–53.

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

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

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

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

Aims. This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection. Methods. A total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years’ clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery. Results. The rate of PJI for all identified MoM THAs was 3.5% (41/1,171), with a mean follow-up of 10.9 years (2.0 to 20.4). Of the patients included in the final cohort, 8.2% (27/328) had PJI, with a mean follow-up of 12.2 years (2.3 to 20.4). Among this cohort, 31.1% (102/328) had a history of pseudotumour. The rate of PJI in these patients was 14.7% (15/102), which was greater than those without pseudotumour, 5.3% (12/226) (p = 0.008). Additionally, logistic regression analysis showed an association between history of pseudotumour and PJI (odds ratio 4.36 (95% confidence interval 1.77 to 11.3); p = 0.002). Optimal diagnostic cutoffs for PJI in patients with history of pseudotumour versus those without were 33.1 mm/hr and 24.5 mm/hr for ESR and 7.37 mg/dl and 1.88 mg/dl for CRP, respectively. Conclusion. Patients with history of pseudotumour secondary to MoM THA had a higher likelihood of infection than those without. While suspicion of infection should be high for these patients, ESR and CRP cutoffs published by the European Bone and Joint Infection Society may not be appropriate for patients with a history of pseudotumour, as ESR and CRP levels suggestive of PJI are likely to be higher than for those without a pseudotumour. Additional investigation, such as aspiration, is highly recommended for these patients unless clinical suspicion and laboratory markers are low. Cite this article: Bone Joint J 2024;106-B(6):555–564

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

Aims. The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol. Methods. The study involved a retrospective review of our prospectively collected database from which we identified all patients who underwent an intended two-stage revision for PJI of the hip. All patients had a diagnosis of PJI according to the major criteria of the Musculoskeletal Infection Society (MSIS) 2013, a minimum five-year follow-up, and were assessed using the MSIS working group outcome-reporting tool. The outcomes were grouped into ‘successful’ or ‘unsuccessful’. Results. A total of 299 two-stage revision THAs in 289 patients met the inclusion criteria, of whom 258 (86%) proceeded to second-stage surgery. Their mean age was 68.1 years (28 to 92). The median follow-up was 10.7 years (interquartile range (IQR) 6.3 to 15.0). A 91% success rate was seen in those patients who underwent reimplantation, decreasing to 86% when including those who did not proceed to reimplantation. The median duration of postoperative systemic antibiotics following the first stage was five days (IQR 5 to 9). There was no significant difference in outcome between those patients who were treated with antibiotics for ≤ 48 hours (p = 0.961) or ≤ five days (p = 0.376) compared with those who were treated with longer courses. Greater success rates were seen for Gram-positive PJIs (87%) than for Gram-negative (84%) and mixed-Gram PJIs (72%; p = 0.098). Conclusion. Aggressive surgical debridement with a high local concentration of targeted antibiotics at the time of first-stage revision surgery for PJI of the hip, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship, and reduced hospital costs. Cite this article: Bone Joint J 2023;105-B(5):511–517

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

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

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

Aims. Periprosthetic joint infection (PJI) in total hip arthroplasty in the elderly may occur but has been subject to limited investigation. This study analyzed infection characteristics, surgical outcomes, and perioperative complications of octogenarians undergoing treatment for PJI in a single university-based institution. Methods. We identified 33 patients who underwent treatment for PJIs of the hip between January 2010 and December 2019 using our institutional joint registry. Mean age was 82 years (80 to 90), with 19 females (57%) and a mean BMI of 26 kg/m. 2. (17 to 41). Mean American Society of Anesthesiologists (ASA) grade was 3 (1 to 4) and mean Charlson Comorbidity Index was 6 (4 to 10). Leading pathogens included coagulase-negative Staphylococci (45%) and Enterococcus faecalis (9%). Two-stage exchange was performed in 30 joints and permanent resection arthroplasty in three. Kaplan-Meier survivorship analyses were performed. Mean follow-up was five years (3 to 7). Results. The two-year survivorship free of any recurrent PJI was 72% (95% confidence interval (CI) 56 to 89; 18 patients at risk). There were a total of nine recurrent PJIs at a mean of one year (16 days to eight years), one for the same pathogen as at index infection. One additional surgical site infection was noted at two weeks, resulting in a 69% (95% CI 52 to 86; 17 patients at risk) survivorship free of any infection at two years. There were two additional revisions for dislocations at one month each. As such, the two-year survivorship free of any revision was 61% (95% CI 42 to 80; 12 patients at risk). In addition to the aforementioned revisions, there was one additional skin grafting for a decubitus ulcer, resulting in a survivorship free of any reoperation of 54% (95% CI 35 to 73; ten patients at risk) at two years. Mean Clavien-Dindo score of perioperative complications was two out of five, with one case of perioperative death noted at six days. Conclusion. Octogenarians undergoing surgery for PJI of the hip are at low risk of acute mortality, but are at moderate risk of other perioperative complications. One in two patients will undergo a reoperation within two years, with 70% attributable to recurrent infections. Cite this article: Bone Joint J 2023;105-B(2):135–139

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

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

Aims. 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

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

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

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

Aims. Uncemented implants are now commonly used at reimplantation of a two-stage revision total hip arthoplasty (THA) following periprosthetic joint infection (PJI). However, there is a paucity of data on the performance of the most commonly used uncemented femoral implants – modular fluted tapered (MFT) femoral components – in this setting. This study evaluated implant survival, radiological results, and clinical outcomes in a large cohort of reimplantation THAs using MFT components. Methods. We identified 236 reimplantation THAs from a single tertiary care academic institution from September 2000 to September 2020. Two designs of MFT femoral components were used as part of an established two-stage exchange protocol for the treatment of PJI. Mean age at reimplantation was 65 years (SD 11), mean BMI was 32 kg/m. 2. (SD 7), and 46% (n = 109) were female. Mean follow-up was seven years (SD 4). A competing risk model accounting for death was used. Results. The 15-year cumulative incidence of any revision was 24%. There were 48 revisions, with the most common reasons being dislocation (n = 25) and infection (n = 16). The 15-year cumulative incidence of any reoperation was 28%. Only 13 revisions involved the fluted tapered component (FTC), for a 15-year cumulative incidence of any FTC revision of 8%. Only two FTCs were revised for aseptic loosening, resulting in a 15-year cumulative incidence of FTC revision for aseptic loosening of 1%. Stem subsidence ≥ 5 mm occurred in 2% of unrevised cases. All stems were radiologically stable at most recent follow-up. Mean Harris Hip Score was 69 (SD 20) at most recent follow-up. Conclusion. This series demonstrated that MFT components were durable and reliable in the setting of two-stage reimplantation THA for infection. While the incidence of aseptic loosening was very low, the incidence of any revision was 24% at 15 years, primarily due to dislocation and recurrent PJI. Cite this article: Bone Joint J 2024;106-B(5 Supple B):125–132

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

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

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

Aims. The 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

Aims. This study aimed to compare the effect of antibiotic-loaded bone cement (ALBC) versus plain bone cement (PBC) on revision rates for periprosthetic joint infection (PJI) and all-cause revisions following primary elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods. MEDLINE, Embase, Web of Science, and Cochrane databases were systematically searched for studies comparing ALBC versus PBC, reporting on revision rates for PJI or all-cause revision following primary elective THA or TKA. A random-effects meta-analysis was performed. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID CRD42018107691). Results. Nine studies and one registry report were identified, enabling the inclusion of 371,977 THA and 671,246 TKA. Pooled analysis for THA demonstrated ALBC was protective against revision for PJI compared with PBC (relative risk (RR) 0.66, 95% confidence interval (CI) 0.56 to 0.77; p < 0.001), however, no differences were seen for all-cause revision rate (RR 0.62, 95% CI 0.35 to 1.09; p = 0.100). For TKA, there were no significant differences in revision rates for PJI or all causes between ALBC and PBC (RR 0.92, 95% CI 0.59 to 1.45; p = 0.730, and RR 0.73, 95% CI 0.53 to 1.02; p = 0.060, respectively). Conclusion. ALBC demonstrated a protective effect against revision for PJI compared with PBC in THA with no difference in all-cause revisions. No differences in revision rates for PJI and all-cause revision between ALBC and PBC for TKA were observed. Cite this article: Bone Joint J 2021;103-B(1):7–15

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

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

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

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

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

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

Aims. Large bone defects resulting from osteolysis, fractures, osteomyelitis, or metastases pose significant challenges in acetabular reconstruction for total hip arthroplasty. This study aimed to evaluate the survival and radiological outcomes of an acetabular reconstruction technique in patients at high risk of reconstruction failure (i.e. periprosthetic joint infection (PJI), poor bone stock, immunosuppressed patients), referred to as Hip Reconstruction In Situ with Screws and Cement (HiRISC). This involves a polyethylene liner embedded in cement-filled bone defects reinforced with screws and/or plates for enhanced fixation. Methods. A retrospective chart review of 59 consecutive acetabular reconstructions was performed by four surgeons in a single institution from 18 October 2018 to 5 January 2023. Cases were classified based on the Paprosky classification, excluding type 1 cases (n = 26) and including types 2 or 3 for analysis (n = 33). Radiological loosening was evaluated by an orthopaedic surgeon who was not the operating surgeon, by comparing the immediate postoperative radiographs with the ones at latest follow-up. Mean follow-up was 557 days (SD 441; 31 to 1,707). Results. Out of the 33 cases analyzed, six (18.2%) constructs required revision, with four revisions due to uncontrolled infection, one for dislocation, and one for aseptic loosening. Among the 27 non-revised constructs, only one showed wider radiolucencies compared to immediate postoperative radiographs, indicating potential loosening. Patients who underwent revision (n = 6) were significantly younger and had a higher BMI compared to those with non-revised constructs (p = 0.016 and p = 0.026, respectively). Sex, race, ethnicity, American Society of Anesthesiologists grade, infection status (patients with postoperative PJI diagnosis (septic) vs patients without such diagnosis (aseptic)), and mean follow-up did not significantly differ between revised and non-revised groups. Conclusion. The HiRISC technique may serve as a feasible short-term (about one to two years) alternative in patients with large acetabular defects, particularly in cases of PJI. Longer follow-up is necessary to establish the long-term survival of this technique. Cite this article: Bone Joint J 2024;106-B(5 Supple B):82–88

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

Aims. 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

Aims. Tibial cones are often utilized in revision total knee arthroplasty (TKA) with metaphyseal defects. Because there are few studies evaluating mid-term outcomes with a sufficient cohort, the purpose of this study was to evaluate tibial cone survival and complications in revision TKAs with tibial cones at minimum follow-up of five years. Methods. A retrospective review was completed from September 2006 to March 2015, evaluating 67 revision TKAs (64 patients) that received one specific porous tibial cone during revision TKA. The final cohort was composed of 62 knees (59 patients) with five years of clinical follow-up or reoperation. The mean clinical follow-up of the TKAs with minimum five-year clinical follow-up was 7.6 years (5.0 to 13.3). Survivorship analysis was performed with the endpoints of tibial cone revision for aseptic loosening, tibial cone revision for any reason, and reoperation. We also evaluated periprosthetic joint infection (PJI), risk factors for failure, and performed a radiological review. Results. The rate of cone revision for aseptic loosening was 6.5%, with an eight-year survival of 95%. Significant bone loss (Anderson Orthopaedic Research Institute grade 3) was associated with cone revision for aseptic loosening (p = 0.002). The rate of cone revision for any reason was 17.7%, with an eight-year survival of 84%. Sixteen percent of knees developed PJI following revision. A pre-revision diagnosis of reimplantation as part of a two-stage exchange protocol for infection was associated with both PJI (p < 0.001) and tibial cone revision (p = 0.001). Conclusion. Mid-term results of tibial cones showed a survivorship free of cone revision for aseptic loosening of 95%. Patients with significant bone loss were more likely to have re-revision for tibial cone failure. Infection was common, and patients receiving cones at reimplantation were more likely to develop PJI and undergo cone revision. Cite this article: Bone Joint J 2021;103-B(6 Supple A):158–164

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

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

Aims. Septic arthritis of the hip often leads to irreversible osteoarthritis (OA) and the requirement for total hip arthroplasty (THA). The aim of this study was to report the mid-term risk of any infection, periprosthetic joint infection (PJI), aseptic revision, and reoperation in patients with a past history of septic arthritis who underwent THA, compared with a control group of patients who underwent THA for OA. Methods. We retrospectively identified 256 THAs in 244 patients following septic arthritis of the native hip, which were undertaken between 1969 and 2016 at a single institution. Each case was matched 1:1, based on age, sex, BMI, and year of surgery, to a primary THA performed for OA. The mean age and BMI were 58 years (35 to 84) and 31 kg/m. 2. (18 to 48), respectively, and 100 (39%) were female. The mean follow-up was 11 years (2 to 39). Results. The ten-year survival free of any infection was 91% and 99% in the septic arthritis and OA groups, respectively (hazard ratio (HR) = 13; p < 0.001). The survival free of PJI at ten years was 93% and 99% in the septic arthritis and OA groups, respectively (HR = 10; p = 0.002). There was a significantly higher rate of any infection at ten years when THA was undertaken within five years of the diagnosis of septic arthritis compared with those in whom THA was undertaken > five years after this diagnosis was made (14% vs 5%, respectively; HR = 3.1; p = 0.009), but there was no significant difference in ten-year survival free of aseptic revision (HR = 1.14; p = 0.485). The mean Harris Hip Scores at two and five years postoperatively were significantly lower in the septic arthritis group compared with the OA group (p = 0.001 for both). Conclusion. There was a ten-fold increased risk of PJI in patients with a history of septic arthritis who underwent THA compared with those who underwent THA for OA with a ten-year cumulative incidence of 7%. The risk of any infection had a strong downward trend as the time interval between the diagnosis of septic arthritis and THA increased, highlighted by a 3.1-fold higher risk when THAs were performed within five years of the diagnosis being made. Cite this article: Bone Joint J 2022;104-B(2):227–234

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

Aims. 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

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. One-stage revision hip arthroplasty for periprosthetic joint infection (PJI) has several advantages; however, resection of the proximal femur might be necessary to achieve higher success rates. We investigated the risk factors for resection and re-revisions, and assessed complications and subsequent re-revisions. Methods. In this single-centre, case-control study, 57 patients who underwent one-stage revision arthroplasty for PJI of the hip and required resection of the proximal femur between 2009 and 2018 were identified. The control group consisted of 57 patients undergoing one-stage revision without bony resection. Logistic regression analysis was performed to identify any correlation with resection and the risk factors for re-revisions. Rates of all-causes re-revision, reinfection, and instability were compared between groups. Results. Patients who required resection of the proximal femur were found to have a higher all-cause re-revision rate (29.8% vs 10.5%; p = 0.018), largely due to reinfection (15.8% vs 0%; p = 0.003), and dislocation (8.8% vs 10.5%; p = 0.762), and showed higher rate of in-hospital wound haematoma requiring aspiration or evacuation (p = 0.013), and wound revision (p = 0.008). The use of of dual mobility components/constrained liner in the resection group was higher than that of controls (94.7% vs 36.8%; p < 0.001). The presence and removal of additional metal hardware (odds ratio (OR) = 7.2), a sinus tract (OR 4), ten years’ time interval between primary implantation and index infection (OR 3.3), and previous hip revision (OR 1.4) increased the risk of proximal femoral resection. A sinus tract (OR 9.2) and postoperative dislocation (OR 281.4) were associated with increased risk of subsequent re-revisions. Conclusion. Proximal femoral resection during one-stage revision hip arthroplasty for PJI may be required to reduce the risk of of recurrent or further infection. Patients with additional metalware needing removal or transcortical sinus tracts and chronic osteomyelitis are particularly at higher risk of needing proximal femoral excision. However, radical resection is associated with higher surgical complications and increased re-revision rates. The use of constrained acetabular liners and dual mobility components maintained an acceptable dislocation rate. These results, including identified risk factors, may aid in preoperative planning, patient consultation and consent, and intraoperative decision-making. Cite this article: Bone Joint J 2021;103-B(11):1678–1685

Aims. Prosthetic joint infection (PJI) remains a serious complication that is associated with high morbidity and costs. The aim of this study was to prepare a systematic review to examine patient-related and perioperative risk factors that can be modified in an attempt to reduce the rate of PJI. Materials and Methods. A search of PubMed and MEDLINE was conducted for articles published between January 1990 and February 2018 with a combination of search terms to identify studies that dealt with modifiable risk factors for reducing the rate of PJI. An evidence-based review was performed on 12 specific risk factors: glycaemic control, obesity, malnutrition, smoking, vitamin D levels, preoperative Staphylococcus aureus screening, the management of anti-rheumatic medication, perioperative antibiotic prophylaxis, presurgical skin preparation, the operating room environment, irrigant options, and anticoagulation. Results. Poor glycaemic control, obesity, malnutrition, and smoking are all associated with increased rates of PJI. Vitamin D replacement has been shown in preliminary animal studies to decrease rates of PJI. Preoperative Staphylococcus aureus screening and appropriate treatment results in decreased rates of PJI. Perioperative variables, such as timely and appropriate dosage of prophylactic antibiotics, skin preparation with chlorohexidine-based solution, and irrigation with dilute betadine at the conclusion of the operation, have all been associated with reduced rates of PJI. Similarly, aggressive anticoagulation and increased operating room traffic should be avoided to help minimize risk of PJI. Conclusion. PJI remains a serious complication of arthroplasty. Surgeons should be vigilant of the modifiable risk factors that can be addressed in an attempt to reduce the risk of PJI

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting. Cite this article: Bone Joint J 2024;106-B(5):425–429

Aims. The aim of this study was to determine the long-term mortality rate, and to identify factors associated with this, following primary and revision knee arthroplasty (KA). Methods. Data from the Scottish Arthroplasty Project (1998 to 2019) were retrospectively analyzed. Patient mortality data were linked from the National Records of Scotland. Analyses were performed separately for the primary and revised KA cohorts. The standardized mortality ratio (SMR) with 95% confidence intervals (CIs) was calculated for the population at risk. Multivariable Cox proportional hazards were used to identify predictors and estimate relative mortality risks. Results. At a median 7.4 years (interquartile range (IQR) 4.0 to 11.6) follow-up, 27.8% of primary (n = 27,474/98,778) and 31.3% of revision (n = 2,611/8,343) KA patients had died. Both primary and revision cohorts had lower mortality rates than the general population (SMR 0.74 (95% CI 0.73 to 0.74); p < 0.001; SMR 0.83 (95% CI 0.80 to 0.86); p < 0.001, respectively), which persisted for 12 and eighteight years after surgery, respectively. Factors associated with increased risk of mortality after primary KA included male sex (hazard ratio (HR) 1.40 (95% CI 1.36 to 1.45)), increasing socioeconomic deprivation (HR 1.43 (95% CI 1.36 to 1.50)), inflammatory polyarthropathy (HR 1.79 (95% CI 1.68 to 1.90)), greater number of comorbidities (HR 1.59 (95% CI 1.51 to 1.68)), and periprosthetic joint infection (PJI) requiring revision (HR 1.92 (95% CI 1.57 to 2.36)) when adjusting for age. Similarly, male sex (HR 1.36 (95% CI 1.24 to 1.49)), increasing socioeconomic deprivation (HR 1.31 (95% CI 1.12 to 1.52)), inflammatory polyarthropathy (HR 1.24 (95% CI 1.12 to 1.37)), greater number of comorbidities (HR 1.64 (95% CI 1.33 to 2.01)), and revision for PJI (HR 1.35 (95% 1.18 to 1.55)) were independently associated with an increased risk of mortality following revision KA when adjusting for age. Conclusion. The SMR of patients undergoing primary and revision KA was lower than that of the general population and remained so for several years post-surgery. However, approximately one in four patients undergoing primary and one in three patients undergoing revision KA died within tenten years of surgery. Several patient and surgical factors, including PJI, were associated with the risk of mortality within ten years of primary and revision surgery. Cite this article: Bone Joint J 2022;104-B(1):45–52

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. 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

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

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

Aims. The purpose of this study was to evaluate unexpected positive cultures in total hip arthroplasty (THA) revisions for presumed aseptic loosening, to assess the prevalence of low-grade infection using two definition criteria, and to analyze its impact on implant survival after revision. Methods. A total of 274 THA revisions performed for presumed aseptic loosening from 2012 to 2016 were reviewed. In addition to obtaining intraoperative tissue cultures from all patients, synovial and sonication fluid samples of the removed implant were obtained in 215 cases (79%) and 101 cases (37%), respectively. Histopathological analysis was performed in 250 cases (91%). Patients were classified as having low-grade infections according to institutional criteria and Musculoskeletal Infection Society (MSIS) International Consensus Meeting (ICM) 2013 criteria. Low-grade infections according to institutional criteria were treated with targeted antibiotics for six weeks postoperatively. Implant failure was defined as the need for re-revision resulting from periprosthetic joint infection (PJI) and aseptic reasons. The mean follow-up was 68 months (26 to 95). Results. Unexpected positive intraoperative samples were found in 77 revisions (28%). Low-grade infection was diagnosed in 36 cases (13%) using institutional criteria and in nine cases (3%) using MSIS ICM 2013 criteria. In all, 41 patients (15%) had single specimen growth of a low-virulent pathogen and were deemed contaminated. Coagulase-negative Staphylococcus and anaerobes were the most commonly isolated bacteria. Implant failure for PJI was higher in revisions with presumed contaminants (5/41, 12%) compared to those with low-grade infections (2/36, 6%) and those with negative samples (5/197, 3%) (p = 0.021). The rate of all-cause re-revision was similar in patients diagnosed with low-grade infections (5/36, 14%) and those with presumed contaminants (6/41, 15%) and negative samples (21/197, 11%) (p = 0.699). Conclusion. Our findings suggest that the presumption of culture contamination in aseptic revision hip arthroplasty may increase the detection of PJI. In this cohort, the presence of low-grade infection did not increase the risk of re-revision. Further studies are needed to assess the relevance of single specimen growth and the benefits of specific postoperative antibiotic regimens. Cite this article: Bone Joint J 2021;103-B(6):1070–1077

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

Aims. Contemporary outcomes of primary total hip arthroplasties (THAs) with highly cross-linked polyethylene (HXLPE) liners in patients with inflammatory arthritis have not been well studied. This study examined the implant survivorship, complications, radiological results, and clinical outcomes of THA in patients with inflammatory arthritis. Methods. We identified 418 hips (350 patients) with a primary diagnosis of inflammatory arthritis who underwent primary THA with HXLPE liners from January 2000 to December 2017. Of these hips, 68% had rheumatoid arthritis (n = 286), 13% ankylosing spondylitis (n = 53), 7% juvenile rheumatoid arthritis (n = 29), 6% psoriatic arthritis (n = 24), 5% systemic lupus erythematosus (n = 23), and 1% scleroderma (n = 3). Mean age was 58 years (SD 14.8), 66.3% were female (n = 277), and mean BMI was 29 kg/m. 2. (SD 7). Uncemented femoral components were used in 77% of cases (n = 320). Uncemented acetabular components were used in all patients. Competing risk analysis was used accounting for death. Mean follow-up was 4.5 years (2 to 18). Results. The ten-year cumulative incidence of any revision was 3%, and was highest in psoriatic arthritis patients (16%). The most common indications for the 15 revisions were dislocations (n = 8) and periprosthetic joint infections (PJI; n = 4, all on disease-modifying antirheumatic drugs (DMARDs)). The ten-year cumulative incidence of reoperation was 6.1%, with the most common indications being wound infections (six cases, four on DMARDs) and postoperative periprosthetic femur fractures (two cases, both uncemented femoral components). The ten-year cumulative incidence of complications not requiring reoperation was 13.1%, with the most common being intraoperative periprosthetic femur fracture (15 cases, 14 uncemented femoral components; p = 0.13). Radiological evidence of early femoral component subsidence was observed in six cases (all uncemented). Only one femoral component ultimately developed aseptic loosening. Harris Hip Scores substantially improved (p < 0.001). Conclusion. Contemporary primary THAs with HXLPE in patients with inflammatory arthritis had excellent survivorship and good functional outcomes regardless of fixation method. Dislocation, PJI, and periprosthetic fracture were the most common complications in this cohort with inflammatory arthritis. Cite this article: Bone Joint J 2023;105-B(7):768–774

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

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. Knowledge on total knee arthroplasties (TKAs) in patients with a history of poliomyelitis is limited. This study compared implant survivorship and clinical outcomes among affected and unaffected limbs in patients with sequelae of poliomyelitis undergoing TKAs. Methods. A retrospective review of our total joint registry identified 94 patients with post-polio syndrome undergoing 116 primary TKAs between January 2000 and December 2019. The mean age was 70 years (33 to 86) with 56% males (n = 65) and a mean BMI of 31 kg/m. 2. (18 to 49). Rotating hinge TKAs were used in 14 of 63 affected limbs (22%), but not in any of the 53 unaffected limbs. Kaplan-Meier survivorship analyses were completed. The mean follow-up was eight years (2 to 19). Results. The ten-year survivorship free from revision was 91% (95% confidence interval (CI) 81 to 100) in affected and 84% (95% CI 68 to 100) in unaffected limbs. There were six revisions in affected limbs: three for periprosthetic femoral fractures and one each for periprosthetic joint infection (PJI), patellar clunk syndrome, and instability. Unaffected limbs were revised in four cases: two for instability and one each for PJI and tibial component loosening. The ten-year survivorship free from any reoperation was 86% (95% CI 75 to 97) and 80% (95% CI 64 to 99) in affected and unaffected limbs, respectively. There were three additional reoperations among affected and two in unaffected limbs. There were 12 nonoperative complications, including four periprosthetic fractures. Arthrofibrosis occurred in five affected (8%) and two unaffected limbs (4%). Postoperative range of motion decreased with 31% achieving less than 90° knee flexion by five years. Conclusion. TKAs in post-polio patients are complex cases associated with instability, and one in four require constraint on the affected side. Periprosthetic fracture was the main mode of failure. Arthrofibrosis rates were high and twice as frequent in affected limbs. Cite this article: Bone Joint J 2023;105-B(6):635–640

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

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

Aims. Periprosthetic joint infection (PJI) is a serious complication of total hip arthroplasty (THA). Different bearing surface materials have different surface properties and it has been suggested that the choice of bearing surface may influence the risk of PJI after THA. The objective of this meta-analysis was to compare the rate of PJI between metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and ceramic-on-ceramic (CoC) bearings. Patients and Methods. Electronic databases (Medline, Embase, Cochrane library, Web of Science, and Cumulative Index of Nursing and Allied Health Literature) were searched for comparative randomized and observational studies that reported the incidence of PJI for different bearing surfaces. Two investigators independently reviewed studies for eligibility, evaluated risk of bias, and performed data extraction. Meta-analysis was performed using the Mantel–Haenzel method and random-effects model in accordance with methods of the Cochrane group. Results. Our search strategy revealed 2272 studies, of which 17 met the inclusion criteria and were analyzed. These comprised 11 randomized controlled trials and six observational studies. The overall quality of included studies was high but the observational studies were at high risk of bias due to inadequate adjustment for confounding factors. The overall cumulative incidence of PJI across all studies was 0.78% (1514/193 378). For each bearing combination, the overall incidence was as follows: MoP 0.85% (1353/158 430); CoP 0.38% (67/17 489); and CoC 0.53% (94/17 459). The meta-analysis showed no significant difference between the three bearing combinations in terms of risk of PJI. Conclusion. On the basis of the clinical studies available, there is no evidence that bearing choice influences the risk of PJI. Future research, including basic science studies and large, adequately controlled registry studies, may be helpful in determining whether implant materials play a role in determining the risk of PJI following arthroplasty surgery. Cite this article: Bone Joint J 2018;100-B:134–42

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

Aims. Unicompartmental knee arthroplasty (UKA) has a higher risk of revision than total knee arthroplasty (TKA), particularly for younger patients. The outcome of knee arthroplasty is typically defined as implant survival or revision incidence after a defined number of years. This can be difficult for patients to conceptualize. We aimed to calculate the ‘lifetime risk’ of revision for UKA as a more meaningful estimate of risk projection over a patient’s remaining lifetime, and to compare this to TKA. Methods. Incidence of revision and mortality for all primary UKAs performed from 1999 to 2019 (n = 13,481) was obtained from the New Zealand Joint Registry (NZJR). Lifetime risk of revision was calculated for patients and stratified by age, sex, and American Society of Anesthesiologists (ASA) grade. Results. The lifetime risk of revision was highest in the youngest age group (46 to 50 years; 40.4%) and decreased sequentially to the oldest (86 to 90 years; 3.7%). Across all age groups, lifetime risk of revision was higher for females (ranging from 4.3% to 43.4% vs males 2.9% to 37.4%) and patients with a higher ASA grade (ASA 3 to 4, ranging from 8.8% to 41.2% vs ASA 1 1.8% to 29.8%). The lifetime risk of revision for UKA was double that of TKA across all age groups (ranging from 3.7% to 40.4% for UKA, and 1.6% to 22.4% for TKA). The higher risk of revision in younger patients was associated with aseptic loosening in both sexes and pain in females. Periprosthetic joint infection (PJI) accounted for 4% of all UKA revisions, in contrast with 27% for TKA; the risk of PJI was higher for males than females for both procedures. Conclusion. Lifetime risk of revision may be a more meaningful measure of arthroplasty outcomes than implant survival at defined time periods. This study highlights the higher lifetime risk of UKA revision for younger patients, females, and those with a higher ASA grade, which can aid with patient counselling prior to UKA. Cite this article: Bone Joint J 2022;104-B(6):672–679

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. The aim of this study was to investigate whether the use of antibiotic-loaded bone cement influenced the risk of revision surgery after primary total hip arthroplasty (THA) for osteoarthritis. Methods. The study involved data collected by the National Joint Registry (NJR) for England and Wales, Northern Ireland and the Isle of Man between 1 September 2005 and 31 August 2017. Cox proportional hazards were used to investigate the association between use of antibiotic-loaded bone cement and the risk of revision due to prosthetic joint infection (PJI), with adjustments made for the year of the initial procedure, age at the time of surgery, sex, American Society of Anesthesiologists (ASA) grade, head size, and body mass index (BMI). We looked also at the association between use of antibiotic-loaded bone cement and the risk of revision due to aseptic loosening or osteolysis. Results. The cohort included 418,857 THAs of whom 397,896 had received antibiotic-loaded bone cement and 20,961 plain cement. After adjusting for putative confounding factors, the risk of revision for PJI was lower in those in whom antibiotic-loaded bone cement was used (hazard ration (HR) 0.79; 95% confidence interval (CI) 0.64 to 0.98). There was also a protective effect on the risk of revision due to aseptic loosening or osteolysis, in the period of > 4.1 years after primary THA, HR 0.57, 95% CI 0.45, 0.72. Conclusion. Within the limits of registry analysis, this study showed an association between the use of antibiotic-loaded bone cement and lower rates of revision due to PJI. The findings support the continued use of antibiotic-loaded bone cement in cemented THA. Cite this article: Bone Joint J 2020;102-B(8):997–1002

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

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

Aims. 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

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. 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

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. In patients with a “dry” aspiration during the investigation of prosthetic joint infection (PJI), saline lavage is commonly used to obtain a sample for analysis. The aim of this study was to investigate prospectively the impact of saline lavage on synovial fluid analysis in revision arthroplasty. Methods. Patients undergoing revision hip (THA) or knee arthroplasty (TKA) for any septic or aseptic indication were enrolled. Intraoperatively, prior to arthrotomy, the maximum amount of fluid possible was aspirated to simulate a dry tap (pre-lavage) followed by the injection with 20 ml of normal saline and re-aspiration (post-lavage). Pre- and post-lavage synovial white blood cell (WBC) count, percent polymorphonuclear cells (%PMN), and cultures were compared. Results. A total of 78 patients had data available for analysis; 17 underwent revision THA and 61 underwent revision TKA. A total of 16 patients met modified Musculoskeletal Infection Society (MSIS) criteria for PJI. Pre- and post-lavage %PMNs were similar in septic patients (87% vs 85%) and aseptic patients (35% vs 39%). Pre- and post-lavage synovial fluid WBC count were far more disparate in septic (53,553 vs 8,275 WBCs) and aseptic (1,103 vs 268 WBCs) cohorts. At a cutoff of 80% PMN, the post-lavage aspirate had a sensitivity of 75% and specificity of 95%. At a cutoff of 3,000 WBCs, the post-lavage aspirate had a sensitivity of 63% and specificity of 98%. As the post-lavage synovial WBC count increased, the difference between pre- and post-lavage %PMN decreased (mean difference of 5% PMN in WBC < 3,000 vs mean difference 2% PMN in WBC > 3,000, p = 0.013). Of ten positive pre-lavage fluid cultures, only six remained positive post-lavage. Conclusion. While saline lavage aspiration significantly lowered the synovial WBC count, the %PMN remained similar, particularly at WBC counts of > 3,000. These findings suggest that in patients with a dry-tap, the %PMN of a saline lavage aspiration has reasonable sensitivity (75%) for the detection of PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):138–144

Aims. Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods. A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results. A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion. Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708

Aims. The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods. Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results. All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion. This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16

Aims. The purpose of this study was to validate the diagnosis of periprosthetic joint infection (PJI) in the Danish Hip Arthroplasty Register (DHR). Patients and Methods. We identified a cohort of patients from the DHR who had undergone primary total hip arthroplasty (THA) since 1 January 2005 and followed them until first-time revision, death, emigration or until 31 December 2012. Revision for PJI, as registered in the DHR, was validated against a benchmark which included information from microbiology databases, prescription registers, clinical biochemistry registers and clinical records. We estimated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for PJI in the DHR alone and in the DHR when combined with microbiology databases. Results. In total, 1382 of the 37 826 primary THAs in the DHR were registered as having been revised for any cause once 26 patients with errors in registration had been excluded: 232 of these were for PJI. For this group, the sensitivity was 67%, specificity 95%, PPV 77%, and NPV 92%. Combining the data from the DHR with those from microbiology databases increased the sensitivity to 90% and also improved specificity (100%), PPV (98%) and NPV (98%). Conclusion. Only two thirds of revisions for PJI were captured in the DHR and only 77% of the PJI reported to the DHR could be confirmed to be infected. . Take home message: combining the data from the DHR with those from microbiology databases substantially improved the validity of the diagnosis of PJI and should enable future register-based studies. Cite this article: Bone Joint J 2016;98-B:320–5

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

Aims. The aim of this study was to assess the effects of transferring patients to a specialized arthroplasty centre between the first and second stages (interstage) of prosthetic joint infection (PJI) of the knee. Patients and Methods. A search of our institutional database was performed to identify patients having undergone two-stage revision total knee arthroplasty (TKA) for PJI. Two cohorts were created: continuous care (CC) and transferred care (TC). Baseline characteristics and outcomes were collected and compared between cohorts. Results. A total of 137 patients were identified: 105 in the CC cohort (56 men, 49 women; mean age 67.9) and 32 in the TC cohort (17 men, 15 women; mean age 67.8 years). PJI organism virulence was greater in the CC cohort (36.2% vs 15.6%; p = 0.030). TC patients had a higher rate of persisting or recurrent infection (53.6% vs 13.4%; p < 0.001), soft-tissue complications (31.3 vs 14.3%; p = 0.030), and reduced requirement for porous metal augments (78.1% vs 94.3%; p = 0.006). Repeat first stage debridement after transfer led to greater need for plastic surgical procedures (58.3% vs 0.0%; p < 0.001). Conclusion. Patient transfer during the interstage of treatment for infected TKA leads to poorer outcomes compared with patients receiving all their treatment at a specialized arthroplasty centre. Cite this article: Bone Joint J 2019;101-B:1087–1092

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

Aims. Modular dual mobility (MDM) acetabular components are often used with the aim of reducing the risk of dislocation in revision total hip arthroplasty (THA). There is, however, little information in the literature about its use in this context. The aim of this study, therefore, was to evaluate the outcomes in a cohort of patients in whom MDM components were used at revision THA, with a mean follow-up of more than five years. Methods. Using the database of a single academic centre, 126 revision THAs in 117 patients using a single design of an MDM acetabular component were retrospectively reviewed. A total of 94 revision THAs in 88 patients with a mean follow-up of 5.5 years were included in the study. Survivorship was analyzed with the endpoints of dislocation, reoperation for dislocation, acetabular revision for aseptic loosening, and acetabular revision for any reason. The secondary endpoints were surgical complications and the radiological outcome. Results. The overall rate of dislocation was 11%, with a six-year survival of 91%. Reoperation for dislocation was performed in seven patients (7%), with a six-year survival of 94%. The dislocations were early (at a mean of 33 days) in six patients, and late (at a mean of 4.3 years) in four patients. There were three intraprosthetic dissociations. An outer head diameter of ≥ 48 mm was associated with a lower risk of dislocation (p = 0.013). Lumbrosacral fusion was associated with increased dislocation (p = 0.004). Four revision THAs (4%) were further revised for aseptic acetabular loosening, and severe bone loss (Paprosky III) at the time of the initial revision was significantly associated with further revision for aseptic acetabular loosening (p = 0.008). Fourteen acetabular components (15%) were re-revised for infection, and a pre-revision diagnosis of reimplantation after periprosthetic joint infection (PJI) was associated with subsequent PJI (p < 0.001). Two THAs had visible metallic changes on the backside of the cobalt chromium liner. Conclusion. When using this MDM component in revision THA, at a mean follow-up of 5.5 years, there was a higher rate of dislocation (11%) than previously reported. The size of the outer bearing was related to the risk of dislocation. There was a low rate of aseptic acetabular loosening. Longer follow-up of this MDM component and evaluation of other designs are warranted. Cite this article: Bone Joint J 2021;103-B(7 Supple B):66–72

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

Aims. To analyse the effectiveness of debridement and implant retention (DAIR) in patients with hip periprosthetic joint infection (PJI) and the relationship to patient characteristics. The outcome was evaluated in hips with confirmed PJI and a follow-up of not less than two years. Patients and Methods. Patients in whom DAIR was performed were identified from our hip arthroplasty register (between 2004 and 2013). Adherence to criteria for DAIR was assessed according to a previously published algorithm. Results. DAIR was performed as part of a curative procedure in 46 hips in 42 patients. The mean age was 73.2 years (44.6 to 87.7), including 20 women and 22 men. In 34 hips in 32 patients (73.9%), PJI was confirmed. In 12 hips, the criteria for PJI were not fulfilled and antibiotics stopped. In 41 (89.1%) of all hips and in 32 (94.1%) of the confirmed PJIs, all criteria for DAIR were fulfilled. In patients with exogenous PJI, DAIR was performed not more than three days after referral. In haematogenous infections, the duration of symptoms did not exceed 21 days. In 28 hips, a single debridement and in six hips two surgical debridements were required. In 28 (87.5%) of 32 patients, the total treatment duration was three months. Failure was noted in three hips (9%). Long-term follow-up results (mean 4.0 years, 1.4 to 10) were available in 30 of 34 (88.2%) confirmed PJIs. The overall successful outcome rate was 91% in 34 hips, and 90% in 30 hips with long-term follow-up results. . Conclusion. Prompt surgical treatment with DAIR, following strict diagnostic and therapeutic criteria, in patients with suspected periprosthetic joint infection, can lead to high rates of success in eradicating the infection. Cite this article: Bone Joint J 2017;99-B:330–6

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

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

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

Periprosthetic joint infection (PJI) is one of the most dreaded complications after arthroplasty surgery; thus numerous approaches have been undertaken to equip metal surfaces with antibacterial properties. Due to its antimicrobial effects, silver is a promising coating for metallic surfaces, and several types of silver-coated arthroplasty implants are in clinical use today. However, silver can also exert toxic effects on eukaryotic cells both in the immediate vicinity of the coated implants and systemically. In most clinically-used implants, silver coatings are applied on bulk components that are not in direct contact with bone, such as in partial or total long bone arthroplasties used in tumour or complex revision surgery. These implants differ considerably in the coating method, total silver content, and silver release rates. Safety issues, such as the occurrence of argyria, have been a cause for concern, and the efficacy of silver coatings in terms of preventing PJI is also controversial. The application of silver coatings is uncommon on parts of implants intended for cementless fixation in host bone, but this option might be highly desirable since the modification of implant surfaces in order to improve osteoconductivity can also increase bacterial adhesion. Therefore, an optimal silver content that inhibits bacterial colonization while maintaining osteoconductivity is crucial if silver were to be applied as a coating on parts intended for bone contact. This review summarizes the different methods used to apply silver coatings to arthroplasty components, with a focus on the amount and duration of silver release from the different coatings; the available experience with silver-coated implants that are in clinical use today; and future strategies to balance the effects of silver on bacteria and eukaryotic cells, and to develop silver-coated titanium components suitable for bone ingrowth. Cite this article: Bone Joint J 2021;103-B(3):423–429

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

Aims. We aimed to report the mid- to long-term rates of septic and aseptic failure after two-stage revision surgery for periprosthetic joint infection (PJI) following total hip arthroplasty (THA). Methods. We retrospectively reviewed 96 cases which met the Musculoskeletal Infection Society criteria for PJI. The mean follow-up was 90 months (SD 32). Septic failure was assessed using a Delphi-based consensus definition. Any further surgery undertaken for aseptic mechanical causes was considered as aseptic failure. The cumulative incidence with competing risk analysis was used to predict the risk of septic failure. A regression model was used to evaluate factors associated with septic failure. The cumulative incidence of aseptic failure was also analyzed. Results. There were 23 septic failures at final follow-up, with a cumulative incidence of 14% (95% confidence interval (CI) 8% to 22%) at one year, 18% (95% CI 11% to 27%) at two years, 22% (95% CI 14% to 31%) at five years, and 23% (95% CI 15% to 33%) at ten years. Having at least one positive culture (hazard ratio (HR) 2.38 (interquartile range (IQR) 1.19 to 4.74); p = 0.013), or a positive intraoperative frozen section (HR 2.55 (IQR 1.06 to 6.15); p = 0.037) was significantly associated with septic failure after reimplantation. With dislocation being the most common cause of aseptic revision (5.2%), the cumulative incidence of aseptic failure was 1% (95% CI 0% to 5%) at one year, 6% (95% CI 1% to 8%) at five years, and 8% (95%CI 3% to 17%) at ten years. Conclusion. If there is no recurrent infection in the five years following reimplantation, the chances of further infection thereafter are remote. While the results of a frozen section may be a reliable guide to the timing of reimplantation, intraoperative culture has, currently, only prognostic value. Surgeons should be aware that instability remains a potential indication for further revision surgery. Cite this article: Bone Joint J 2021;103-B(1):79–86

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

The treatment of peri-prosthetic joint infection (PJI) of the ankle is not standardised. It is not clear whether an algorithm developed for hip and knee PJI can be used in the management of PJI of the ankle. We evaluated the outcome, at two or more years post-operatively, in 34 patients with PJI of the ankle, identified from a cohort of 511 patients who had undergone total ankle replacement. Their median age was 62.1 years (53.3 to 68.2), and 20 patients were women. Infection was exogenous in 28 (82.4%) and haematogenous in six (17.6%); 19 (55.9%) were acute infections and 15 (44.1%) chronic. Staphylococci were the cause of 24 infections (70.6%). Surgery with retention of one or both components was undertaken in 21 patients (61.8%), both components were replaced in ten (29.4%), and arthrodesis was undertaken in three (8.8%). An infection-free outcome with satisfactory function of the ankle was obtained in 23 patients (67.6%). The best rate of cure followed the exchange of both components (9/10, 90%). In the 21 patients in whom one or both components were retained, four had a relapse of the same infecting organism and three had an infection with another organism. Hence the rate of cure was 66.7% (14 of 21). In these 21 patients, we compared the treatment given to an algorithm developed for the treatment of PJI of the knee and hip. In 17 (80.9%) patients, treatment was not according to the algorithm. Most (11 of 17) had only one criterion against retention of one or both components. In all, ten of 11 patients with severe soft-tissue compromise as a single criterion had a relapse-free survival. We propose that the treatment concept for PJI of the ankle requires adaptation of the grading of quality of the soft tissues. Cite this article: Bone Joint J 2014;96-B:772–7

Periprosthetic joint infection (PJI) complicates between 0.5% and 1.2% primary total hip arthroplasties (THAs) and may have devastating consequences. The traditional assessment of patients suffering from PJI has involved the serological study of inflammatory markers and microbiological analysis of samples obtained from the joint space. Treatment has involved debridement and revision arthroplasty performed in either one or two stages. . We present an update on the burden of PJI, strategies for its diagnosis and treatment, the challenge of resistant organisms and the need for definitive evidence to guide the treatment of PJI after THA. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):27–30

Aims. The aim of this review was to evaluate the available literature and to calculate the pooled sensitivity and specificity for the different alpha-defensin test systems that may be used to diagnose prosthetic joint infection (PJI). Materials and Methods. Studies using alpha-defensin or Synovasure (Zimmer Biomet, Warsaw, Indiana) to diagnose PJI were identified from systematic searches of electronic databases. The quality of the studies was evaluated using the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) tool. Meta-analysis was completed using a bivariate model. Results. A total of 11 eligible studies were included. The median QUADAS score was 13 (interquartile range 13 to 13) out of 14. Significant conflicts of interest were identified in five studies. The pooled sensitivity for the laboratory alpha-defensin test was 0.95 (95% confidence interval (CI) 0.91 to 0.98) and the pooled specificity was 0.97 (95% CI 0.95 to 0.98) for four studies with a threshold level of 5.2 mgl. -1. The pooled sensitivity for the lateral flow cassette test was 0.85 (95% CI 0.74 to 0.92) and the pooled specificity was 0.90 (95% CI 0.91 to 0.98). There was a statistically significant difference in sensitivity (p = 0.019), but not specificity (p = 0.47). Conclusion. Laboratory-based alpha-defensin testing remains a promising tool for diagnosing PJI. The lateral flow cassette has a significantly lower performance and pooled results are comparable to the leucocyte esterase test. Further studies are required before the widespread adoption of the lateral flow cassette alpha-defensin test. Cite this article: Bone Joint J 2018;100-B:703–11

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

Aims. The aim of this study was to identify risk factors for prosthetic joint infection (PJI) following total knee arthroplasty (TKA). . Patients and Methods. The New Zealand Joint Registry database was analysed, using revision surgery for PJI at six and 12 months after surgery as primary outcome measures. Statistical associations between revision for infection, with common and definable surgical and patient factors were tested. Results. A total of 64 566 primary TKAs have been recorded on the registry between 1999 and 2012 with minimum follow-up of 12 months. Multivariate analysis showed statistically significant associations with revision for PJI between male gender (odds ratio (OR) 1.85, 95% confidence interval (CI) 1.24 to 2.74), previous surgery (osteotomy (OR 2.45 95% CI 1.2 to 5.03), ligament reconstruction (OR 1.85, 95% CI 0.68 to 5.00)), the use of laminar flow (OR 1.6, 95% CI 1.04 to 2.47) and the use of antibiotic-laden cement (OR 1.93, 95% CI 1.19 to 3.13). There was a trend towards significance (p = 0.052) with the use of surgical helmet systems at six months (OR 1.53, 95% CI 1.00 to 2.34). Conclusion. These findings show that patient factors remain the most important in terms of predicting early PJI following TKA. Furthermore, we found no evidence that modern surgical helmet systems reduce the risk of PJI and laminar flow systems may actually increase risk in TKA. The use of this registry data assists the estimation of the risk of PJI for individual patients, which is important for both informed consent and the interpretation of infection rates at different institutions. . Take home message: Infection rates in TKA are related to both individual patient and surgical factors, and some modern methods of reducing infection may actually increase infection risk. . Cite this article: Bone Joint J 2016;98-B:334–40

Aims. Periprosthetic joint infection (PJI) remains a challenging complication following total hip arthroplasty (THA). It is associated with high levels of morbidity, mortality and expense. Guidelines and protocols exist for the management of culture-positive patients. Managing culture-negative patients with a PJI poses a greater challenge to surgeons and the wider multidisciplinary team as clear guidance is lacking. Patients and Methods. We aimed to compare the outcomes of treatment for 50 consecutive culture-negative and 50 consecutive culture-positive patients who underwent two-stage revision THA for chronic infection with a minimum follow-up of five years. Results. There was no significant difference in the outcomes between the two groups of patients, with a similar rate of re-infection of 6%, five years post-operatively. Culture-negative PJIs were associated with older age, smoking, referral from elsewhere and pre-operative antibiotic treatment. The samples in the culture-negative patients were negative before the first stage (aspiration), during the first-stage (implant removal) and second-stage procedures (re-implantation). Conclusion. Adherence to strict protocols for selecting and treating culture-negative patients with a PJI using the same two-stage revision approach that we employ for complex culture-positive PJIs is important in order to achieve control of the infection in this difficult group of patients. Cite this article: Bone Joint J 2018;(1 Supple A)100-B:3–8

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

Aims. The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee. Methods. A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics. Results. Nine of 72 patients (12.5%) who received antibiotics failed due to further infection compared with 20 of 70 patients (28.6%) who did not receive antibiotics (p = 0.012). Five patients (6.9%) in the treatment group experienced adverse effects related to the administered antibiotics severe enough to warrant discontinuation. Conclusion. This multicentre randomized controlled trial showed that a three-month course of microorganism-directed, oral antibiotics significantly reduced the rate of failure due to further infection following a two-stage revision of total hip or knee arthroplasty for chronic PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):3–9