Aims. Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. Methods. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Results. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain. Cite this article: Bone Joint J 2024;106-B(9):1021–1030

External fixation is widely used in orthopaedic and trauma surgery. Infections around pin or wire sites, which are usually localised, non-invasive, and are easily managed, are common. Occasionally, more serious invasive complications such as necrotising fasciitis (NF) and toxic shock syndrome (TSS) may occur. . We retrospectively reviewed all patients who underwent external fixation between 1997 and 2012 in our limb lengthening and reconstruction programme. A total of eight patients (seven female and one male) with a mean age of 20 years (5 to 45) in which pin/wire track infections became limb- or life-threatening were identified. Of these, four were due to TSS and four to NF. Their management is described. A satisfactory outcome was obtained with early diagnosis and aggressive medical and surgical treatment. . Clinicians caring for patients who have external fixation and in whom infection has developed should be aware of the possibility of these more serious complications. Early diagnosis and aggressive treatment are required in order to obtain a satisfactory outcome. Cite this article: Bone Joint J 2015;97-B:1296–1300

Aim. The time to onset of symptoms after fracture fixation is still commonly used to classify fracture-related infections (FRI). Early infections (<2 weeks) can often be treated with debridement, systemic antibiotics, irrigation, and implant preservation (DAIR). Late infections (>10 weeks) typically require implant removal as mature, antibiotic-tolerant biofilms have formed. However, the recommendations for delayed infections (2–10 weeks) are not clearly defined. Here, infection healing and bone healing in early and delayed FRI is investigated in a rabbit model with a standardized DAIR procedure. Method. Staphylococcus aureus was inoculated into 17 rabbits after plate osteosynthesis in a humerus osteotomy. The infection developed either one week (early group, n=6) or four weeks (delayed group, n=6) before a standardized DAIR procedure and microbiological analysis were performed. Systemic antibiotics were administered for six weeks (two weeks: Nafcillin+Rifampin, four weeks: Levofloxacin+Rifampin). A control group (n=5) also underwent a revision operation (debridement and irrigation) after four weeks, but received no antibiotic treatment. Rabbits were euthanized seven weeks after the revision operation. Bone healing was assessed using a modified radiographic union score for tibial fractures (mRUST). After euthanasia, a quantitative microbiological examination of the entire humerus, adjacent soft tissues, and implants was performed. Results. All animals were infected at the time of revision surgery, with the bacterial load in the early group (especially in soft tissues) being greater than in the delayed group and control group. This indicates infiltration of bacteria into areas that are more difficult to reach after four weeks of debridement. The infection was eradicated in all animals in both the early and delayed groups at euthanasia, but not in the control group (CFU median (IQR): 2.1×10. 7. (1.3×10. 7. -2.6×10. 7. ). The osteotomy healed in the early group, while bone healing was significantly impaired in both the delayed group and control group (mRUST median (IQR): early group: 16 (14–16), delayed group: 7.5 (6–10), control: 7 (5.5–9); early vs. delayed: p=0.0411, early vs. control p=0.0065). Conclusion. The maturation of the infection between the first and fourth week does not affect the success of infection eradication in this rabbit FRI model. However, bone healing appears to be impaired with increasing duration of infection

Aims. Fracture-Related Infection (FRI) is a severe complication caused by microbial infection of bone. It is imperative to gain more insight into the potentials and limitations of Debridement, Antibiotics and Implant Retention (DAIR) to improve future FRI treatment. The aims of this study were to: 1) determine how time to surgery affects the success rate of DAIR procedures of the lower leg performed within 12 weeks after the initial fracture fixation operation and 2) evaluate whether appropriate systemic antimicrobial therapy affects the success rate of a DAIR procedure. Methods. This multinational retrospective cohort study included patients of at least 18-years of age who developed an FRI of the lower leg within 12 weeks after the initial fracture fixation operation, between January 1st 2015 to July 1st 2020. DAIR success was defined by the absence of recurrence of infection, preservation of the affected limb and retention of implants during the initial treatment. The antimicrobial regimen was considered appropriate if the pathogen(s) was susceptible to the given treatment at the correct dose as per guideline. Logistic regression modelling was used to assess factors that could contribute to the DAIR success rate. Results. A total of 120 patients were included, of whom 70 DAIR patients and 50 non-DAIR patients. Within a median follow-up of 35.5 months, 21.4% of DAIR patients developed a recurrent FRI compared to 12.0% of non-DAIR patients. The DAIR procedure was successful in 45 patients (64.3%). According to the Willenegger and Roth classification, DAIR success was achieved in 66.7% (n=16/24) of patients with an early infection (<2 weeks), 64.4% (n=29/45) of patients with a delayed infection (2–10 weeks) and 0.0% (0/1) of patients with a late infection (>10 weeks). Univariate analysis showed that the duration of infection was not associated with DAIR success in this cohort (p=0.136; OR: 0.977; 95%CI: [0.947–1.007]). However, an appropriate antimicrobial regimen was associated with success of DAIR (p=0.029; OR: 3.231; 95%CI: [1.138–9.506]). Conclusions. Although the results should be interpreted with caution, an increased duration of infection was not associated with a decreased success rate of a DAIR procedure in patients with FRI of the lower leg. The results of this study highlight the multifactorial contribution to the success of a DAIR procedure and emphasize the importance of adequate antimicrobial treatment. Therefore, time to surgery should not be the only key-factor when considering a DAIR procedure to treat FRI

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

Aim. The aim of this investigation was to compare risk of infection in both cemented and cementless hemiarthroplasty (HA) as well as total hip arthroplasty (THA) following femoral neck fracture. Methods. Data collection was performed using the German Arthroplasty Registry (EPRD) In HA and THA following femoral neck fracture fixation method was divided into cemented and cementless protheses and paired according to age, sex, body mass index (BMI), and the Elixhauser score using Mahalanobis distance matching. Results. Overall in 13,612 cases of intracapsular femoral neck fracture, with 9,110 (66.9 %) HAs and 4502 (33.1 %) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared to cementless fixated prosthesis (p=0.013). In patients with THA no statistical difference between cemented and cementless prothesis was registered, however after one year 2.4 % of infections were detected in cementless and 2.1 % in cemented THA. In the subpopulation of HA after one year 1.9 % of infections were registered in cemented and 2.8 % in cementless HA. BMI (p=0.001) and Elixhauser-Comorbidity-Score (p<0.003) were identified as risk factors of PJI, while in THA also cemented prosthesis demonstrated within the first 30 days an increased risk (HR=2.728; p=0.010). Conclusion. The rate of infection after intracapsular femoral neck fracture was significantly reduced in patients treated by antibiotic-loaded cemented hemiarthroplasty. In particular for patients with multiple risk factors for the development of a PJI the usage of antibiotic-loaded bone cement seems to be a reasonable procedure for prevention of infection

Aim. The current antibiotic treatment of periprosthetic joint infection (PJI) is optimized by measuring concentrations in plasma. However, it remains unclear whether effective concentrations of the antibiotics are reached at the site of PJI. Nonetheless, adequate target site concentrations are important to achieve effective eradication of the micro-organism. In order to determine the efficacy of cefuroxime and flucloxacillin in synovial fluid, synovial tissue and bone tissue in relation to the minimal inhibitory concentration (MIC) of the pathogen causing the PJI, we perform a pharmacokinetic/pharmacodynamic (PK/PD) study. Therefore, we aimed to develop validated analytical methods for analysis of cefuroxime and flucloxacillin in synovial fluid, synovial tissue and bone tissue. Method. Blank samples of synovial fluid, synovial tissue and bone tissue were obtained by orthopedic surgeons during surgery. For validation the samples of each matrix were spiked with both cefuroxime and flucloxacillin. Synovial tissue and bone tissue was pulverized with a mikro-dismembrator. Samples were kept frozen at −20°C until analysis. After a sample preparation quantification of cefuroxime and flucloxacillin in each matrix was performed on the ultra-performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS). Stable-isotope-labeled meropenem-d6 served as internal standard. The linearity, limits of quantification, accuracy and precision and carry-over were determined for all methods separately. The methods were validated according to the European Medicine Agency (EMA) and Food and Drug Administration (FDA) guidelines on bioanalytical method validation. Results. These methods were successfully validated for cefuroxime and flucloxacillin quantification in all matrices according to the EMA and FDA guidelines. The limits of quantification were adequate to cover potential cefuroxime and flucloxacillin concentration in synovial fluid, synovial tissue and bone tissue as described in literature, with a range of 1–100mg/L for synovial fluid and 1–20 µg/g for synovial tissue and bone tissue (r >0.995). Accuracy and within-run precision were validated according to acceptance values (RSD <15%). Carry over was less than 20%. Matrix effects and recovery were investigated for synovial fluid. The results were within the range of 80–120%. Conclusions. The results of the validation fall within the limits of quantification according to the EMA and FDA guidelines. Therefore, these methods can be applied during a PK/PD study to discover the exposure of antibiotics in synovial fluid, synovial tissue and bone tissue at the site of infection in patients with a PJI

Aim. Accurate diagnosis is key in correctly managing prosthetic joint infection (PJI). Our aim is to compare the preoperative performance of three PJI definitions comparing it to definitive postoperative classification. Method. This is a multicenter retrospective study of patients who have undergone total hip or knee revision surgery in four different European institutions. For this specific study, cases with no preoperative synovial fluid differential leukocyte count and less than four intraoperative microbiology samples were excluded. Cases were classified using the 2021 EBJIS, the 2018 International Consensus Meeting (ICM) and the 2013 Musculoskeletal Infection Society (MSIS) PJI definitions. Preoperative classification was based on clinical features, inflammatory markers and synovial fluid leukocyte count and microbiology results. Results. Preoperative and definitive PJI classification status of the 384 patients included are presented in figure 1. EBJIS definition showed the highest agreement between preoperative and definitive classification (k=0.86, CI95% 0.81–0.90, p<0.001) compared to ICM 2018 (k=0.80, CI95% 0.75–0.84, p<0.001) or MSIS 2013 (k=0.70, CI95% 0.62–0.77, p<0.001). Compared to its respective definitive classification: EBJIS preoperative unlikely result shows 86.8% (95%CI 81.3%–91.2%) sensitivity and 87.7% (95%CI 83.3%–91.1%) negative predictive value (NPV); ICM 2018 preoperative not infected result shows 83.5% (95%CI 77.4%–88.5%) sensitivity and 86.2% (95%CI 81.9%–88.6%) NPV and; MSIS 2013 preoperative not infected result shows 63.9% (95%CI 55.0%–72.1%) sensitivity and 84.3% (95%CI 81.1%–87.1%) NPV. Around half of the preoperative EBJIS likely (45.8%) and ICM 2018 inconclusive (54.5%) turn out to be infected postoperatively. If we consider the more sensitive definition (EBJIS) as the gold standard: ICM 2018 preoperative not infected result shows 75.1% (95%CI 68.5%–81.0%) sensitivity and 78.3% (95%CI 73.9%–82.2%) NPV and; MSIS 2013 preoperative not infected result shows 42.1% (95% CI 35.2%–49.4%) sensitivity and 62.0% (59.2%–64.8) NPV. Conclusions. The EBJIS 2021 definition is not only the most sensitive definition as it was shown to be the most effective in preoperatively ruling out PJI when there is a negative result. For any tables or figures, please contact the authors directly

Aim. There have been many attempts to define the criteria by which prosthetic joint infection (PJI) is diagnosed. Our aim is to validate the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI. Method. This is a multicenter retrospective study of patients who have undergone total hip or knee revision surgery in four different European institutions between 2013–2018. Cases with less than four intraoperative microbiology samples; no preoperative/intraoperative synovial fluid differential leukocyte count or intraoperative histology were excluded. Minimum follow-up of at least two years after revision surgery if no subsequent infection and/or the need for implant removal was also required. All cases were classified using the 2021 EBJIS, the 2018 International Consensus Meeting (ICM) and the 2013 Musculoskeletal Infection Society (MSIS) PJI definitions. Results. Definitive PJI classification according to the different definitions of the 507 patients included are presented in table 1. The EBJIS definition classifies 40.4%(205/507) of the cases as confirmed infections compared to 33.9%(p=0.038) and 29.4%(p<0.001) in 2018 ICM and 2013 MSIS classifications respectively. Compared to 2018 ICM classification it also offers significantly less undetermined cases – 5.0% vs. 11.4%(p<0.001). Free from infection Kaplan-Meyer survival curve shows significantly better outcome for EBJIS unlikely compared to confirmed subgroup(p=0.031). EBJIS likely subgroup survival is not significantly different from unlikely(p=0.529) or confirmed(p=0.717) cohorts. Among the MSIS not infected cohort the newly classified EBJIS confirmed/likely cases present higher subsequent infection rate (albeit not statistically significant) when compared to EBJIS infection unlikely cases − 16.0%(13/81) vs. 10.1%(28/277). This subsequent PJI rate is similar to the MSIS infected cohort. A similar trend is not obvious within ICM 2018 not infected subgroup. Conclusions. The EBJIS 2021 definition is shown to be the most sensitive definition while also offering a smaller number of undetermined cases. Newly diagnosed infections seem to have a similar prognosis as “classically” infected cases. For any tables or figures, please contact the authors directly

Aim. Synovial fluid investigation is the best alternative to diagnose prosthetic joint infection (PJI) before adequate microbiological/histology sampling during revision surgery. Although accurate preoperative diagnosis is certainly recommended, puncturing every patient before revision arthroplasty raises concerns about safety and feasibility issues especially in difficult to access joint (e.g., hip), that often require OR time and fluoroscopy/ultrasound guidance. Currently there is no clear guidelines regarding optimal indications to perform preoperative joint aspiration to diagnose PJI before revision surgery. The main goal of this study is to determine the accuracy of our institutional criteria using the new European Bone and Joint Infection Society (EBJIS) PJI definition. Method. We retrospectively evaluated every single- or first-stage for presumed aseptic or known infected revision total hip/knee arthroplasty procedures between 2013–2020. Preoperative clinical and laboratory features were systematically scrutinized. Cases with insufficient information for accurate final PJI diagnosis (i.e., no perioperative synovial fluid examination or no multiple cultures including sonication of removed implant) were excluded. Preoperative joint aspiration is recommended in our institution if any of the following criteria are met: 1) elevated CRP and/or ESR; 2) early failure (<2 years) or repeat failure; 3) high clinical suspicion/risk factors are present. Performance of such criteria were compared against final postoperative EBJIS definition PJI diagnosis. Results. A total of 364 revision THAs or TKAs were performed during the study period. After excluding 258 cases with insufficient information, a total of 106 patients were ultimately included. 38 (35,8 %) were classified as confirmed infections, 10 (9.4 %) as likely infected and 58 (54.7%) as infection unlikely. Of those, 37 confirmed infection cases, 9 likely infected cases and 32 infection unlikely cases did have indication for preoperative synovial fluid collection before revision surgery. Institutional criteria showed 95.8 % Sensitivity, 44.83 % Specificity, 92.9 % Negative Predictive Value (NPV) and 59 % Positive Predictive Value (PPV). Conclusions. Sensitivity and NPV of the aforementioned institutional criteria are very high even with the use of the more sensitive EBJIS PJI definition. As such they seem to be a valid alternative in selecting patients that should be punctured before revision arthroplasty. They identify the vast majority of infected patients while saving a significant number of patients from unnecessary procedures

Aim. Treatment algorithms for fracture-related nonunion depend on the presence or absence of bacterial infection. However, the manifestation of septic nonunion varies. Low-grade infections, unlike manifest infections, lack clinical signs of infection and present similarly to aseptic nonunion. The clinical importance of low-grade infection in nonunion is not entirely clear. Therefore, the aim of this study was to evaluate the clinical relevance of low-grade infection in the development and management of femoral or tibial nonunion. Method. A prospective, multicenter clinical study enrolled patients with nonunion and regular healed fractures. Preoperatively, complete blood count without differential, C-reactive protein (CRP), and procalcitonin were obtained, clinical signs of infection were recorded, and a suspected septic or aseptic diagnosis was made based on history and clinical examination. During surgical nonunion revision or routine implant removal, tissue samples were collected for microbiology and histopathology, and osteosynthesis material for sonication. Nonunion patients were followed for 12 months. Definitive diagnosis of “septic” or “aseptic” nonunion was made according to diagnostic criteria for fracture-related infection, considering the results of any further revision surgery during follow-up. Results. 34 patients with regular healed fractures were included. 62 nonunion patients were diagnosed as aseptic, 22 with manifest, and 23 with low-grade infection. The positive predictive value was 88% and the negative predictive value 72% for the suspected diagnosis. The nonunion groups had significantly higher CRP levels than the regular healer group. Differentiation between septic and aseptic nonunion based on blood values was not possible. Low-grade infection demonstrated less frequently histopathologic signs of infection than manifest infection (22% vs. 50%, p=0.048), with 15% of regular healers having histopathologic signs of infection. Cutibacterium acnes was less present in manifest compared to low-grade infection (p=0.042). Healing rates for septic nonunion involving C. acnes were significantly lower for manifest infection (20%) than for low-grade infection (100%, p=0.002). Patients with low-grade infection were treated with systemic antibiotics less frequently than patients with manifest infection (p=0.026), with no significant difference in healing rate (83% vs. 64%), which was slightly lower for low-grade infection than for aseptic nonunion (90%). Conclusions. Low-grade infections play a significant role in nonunion development and are difficult to diagnose preoperatively due to the lack of clinical signs of infection and unremarkable blood counts. However, our results imply that for low-grade infections, antibiotic therapy may not always be mandatory to heal the nonunion. This study was supported by the German Social Accident Insurance (FF-FR0276)

Purpose. Fracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI. Methods. Over a five-year period, FRI patients treated at the University Hospitals of Leuven, Belgium, were retrospectively included. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early (<2 weeks after implantation), delayed (2–10 weeks) or late-onset (> 10 weeks) FRI. Results. One hundred ninety-one patients with 194 FRIs, mainly involving the tibia (23.7%) and femur (18.6%), were included. Staphylococcus aureus was the most frequently isolated pathogen, regardless of time to onset (n=61; 31.4%), followed by S. epidermidis (n=50; 25.8%) and non-epidermidis coagulase-negative staphylococci (n=35; 18.0%). Polymicrobial infections (n=49; 25.3%), mainly involving Gram-negative bacilli (n=32; 65.3%), were less common than monomicrobial infections (n=138; 71.1%). Virulent pathogens in monomicrobial FRIs were more likely to cause pus or purulent discharge (n=45;54.9%; p=0.002) and fistulas (n=21;25.6%; p=0.030). Susceptibility to piperacillin/tazobactam for GNB was 75.9%. Vancomycin covered 100% of Gram-positive cocci. Conclusion. The high frequency of polymicrobial infections, including Enterobacterales and enterococci, should be considered when choosing an empirical regimen, especially for early FRI. However, since antibiotic stewardship is the cornerstone of good antibiotic practice, overuse and misuse of broad-spectrum empiric therapy should be avoided at all costs. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy

Aim. This is the first study to directly compare the clinical outcome of debridement, antimicrobials and implant retention (DAIR) with stabilization using new internal fixation after debridement, for patients with Fracture-related Infection (FRI). Method. Consecutive patients with FRI Consensus confirmed FRI had single-stage surgery with tissue sampling, debridement, stabilization, antimicrobial therapy and skin closure. All cases had FRIs which were unhealed at surgery. When existing implants were stable, the implant was retained but loose implants or fractures with poor reduction had implant removal and refixation with new implants. All patients had the same empiric and definitive antibiotics, the same diagnostic criteria and outcome assessment at least one year after surgery. Failure was defined as infection recurrence, reoperation or lack of fracture consolidation at one year. Results. Seventy-one patients were studied (40 DAIRs and 31 new implants, including 10 exchange nails). The two groups were well matched for age, duration of infection, BACH complexity, microbiology, bone involved and need for flap coverage. Ten patients (13.7%) died before the endpoint. Mortality was similar in both groups (DAIR 14.1% vs New Metalware 12.9%; p=0.801) but DAIR of IM nails had a higher mortality at 40% (p=0.011). Sixty-one patients were followed-up for a mean of 3.32 years (1.04-9.43). Infection was eradicated in 23/34 (67.6%) DAIR patients and 24/27 (88.9%) with new metalware (p=0.049). Overall rates of infection-free union were similar in both groups (58.8% vs 77.8%; p=0.117). DAIR of plates had significantly fewer infection-free unions compared to removal and implantation of new plates (DAIR 57.1% vs NM 91.7%; p=0.033). Conclusion. Implantation of new metalware had better eradication of infection and a strong trend towards better union rates. Treating FRI with retained or new metalware had a substantial mortality (13.7%). Choosing DAIR did not reduce this mortality and these patients more often required further surgery to treat residual infection and secure union

Aim. One of the most severe complications of primary total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). Nowadays, the use of antibiotic-loaded cement for prevention of infection is still controversial. The aim of the present study is to evaluate the use of an antibiotic-loaded cement to reduce the infection rate in primary total knee arthroplasty. Method. Prospective randomized study, with 2893 cemented total knee arthroplasties performed between 2005 and 2010 in our institution. Two different groups were formed depending on which bone cement was used, without antibiotic (the control group) or loaded with erythromycin and colistin (the study group). All patients received the same systemic prophylactic antibiotics. The patients were followed for a minimum of twelve months. The rate of infection was analyzed according to the criteria of the Centers for Disease Control and Prevention (CDC). Results. In 1452 patients the prosthetic components were fixed using bone cement without antibiotic and in 1441 patients bone cement loaded with erythromycin and colistin was used. There were no differences between both groups in terms of demographic data (age, sex and BMI), either in operating time (p>0,05). The rate of infection was similar in both groups, being 2,0% (n=29) in the control group and 1,7% in the study group (p=0,58) at 8,7 years (SD 5,1) of follow up. In terms of prosthetic revision due to any cause (infected or aseptic), there wasn't differences between groups, performing a total of 61 revision arthroplasties in control group and 68 in study group (p>0,05). Moreover, we analyzed the erythromycin resistance rate, being no differences between both groups (p=0.6). Conclusions. The use of erythromycin and colistin-loaded bone cement in total knee arthroplasty did not lead to a decrease in the rate of infection when systemic prophylactic antibiotics were used, a finding that suggests that its use would not be indicated in the general population

Background and purpose. Previous publications have reported an increased but levelling out risk of revision for infection after total hip arthroplasty (THA) in Norway. We assessed the changes in risk of major (cup and/or stem, 1- or 2-stage) and minor revisions (debridement, exchange of modular parts, antibiotics and implant retention (DAIR)) for infection after primary THAs reported to the Norwegian Arthroplasty Register (NAR) over the period 2005-2022. Patients and methods. Primary THAs reported to the NAR from 2005 to 2022 were included. Time was stratified into time periods (2005-2009, 2010-2018, 2019-2022) based on a previous publication. Cox regression analyses, adjusted for sex, age and ASA-classification, with the first revision for infection were performed. Results. 140,338 primary THAs met the inclusion criteria. 1.3% (1,785) were revised for infection during the study period. 0.5% (638) had major revisions, whereas 0.8% (1,147) had DAIRs for infection. The risk of revision for infection was 1.2 (95%CI 1.1-1.4) for 2010-2018 and 1.0 (0.8-1.1) for 2019-2022 compared to 2005-2009. Compared to 2010-2018, the risk of revision for infection was 0.8 (0.7-0.9) for 2019-2022. The risk of DAIR for infection was 1.5 (1.3-1.9) for 2010-2018 and 1.2 (1.0-1.4) for 2019-2022 compared to 2005-2009. Compared to 2010-2018, the risk of DAIR for infection was 0.8 (0.7-0.9) for 2019-2022. The risk of major revision for infection was 0.8 (0.7-1.0) for 2010-2018 and 0.8 (0.6-1.0) for 2019-2022 compared to 2005-2009. Interpretation. The overall risk of revision for infection after THA, in Norway, has decreased in the period 2019-2022. The risk for DAIR initially increased in the period 2005-2009, levelled out 2010-2018 before starting to decrease in 2019-2022. The risk of major revision for infection was reduced in the period 2005-2009 before levelling out. This shows changes in revision strategies, but may also reflect a true decrease in periprosthetic joint infection

Aims. Despite numerous studies on periprosthetic joint infections (PJI), there are no robust data on the risk factors and timing of metachronous infections. This study was performed to answer the following questions: 1) Is there any difference of manifestation time of metachronous PJIs between different localizations of multiple artificial joints? 2) Can we identify any specific risk factor for metachronous PJIs for different localizations of multiple artificial joints?. Methods. Between January 2010 and December 2018, 661 patients with more than one prosthetic joint at the time of PJI surgical treatment were recruited. Seventy-one developed metachronous PJI after a mean time interval of 101.4 months (range 37.5 to 161.5 months). The remaining patients were chosen as control group. The diagnosis of the PJI, including the metachronous PJI, was made according to the Muscoloskeletal Infection Society (MSIS) criteria. The metachronous infections were divided in group 1: metachronous infections in the same extremity (e.g. right hip and right knee); group 2: metachronous infections of the other extremity (e.g. right knee and left hip); group 3: metachronous infections of the lower extremity and upper extremity (e.g. right knee and left shoulder). Results. We identified 32 PJI cases in group 1, 38 in group 2 and 1 in group 3. Diabetes mellitus was found higher in the metachronous infections (p<0.05). Rate of same side infection was significantly higher compared to contralateral and upper and lower infection (p<0.05). Time interval of metachrononous infection development was faster in same-side infections. Same bacteria sample rate between primary PJI and metachronous PJI in same side infections (21/32) was significantly higher than in the contralateral PJI group (13/38, p<0.05). Conclusions. The current study underlined that the risk of metachronous infections are relatively high, particularly in the cases of prostheses on the same side

Aim. In recent years, many studies on revision for infection after arthroplasty have been published. In national arthroplasty registers, revision for infection is defined as surgical debridement, with or without removal or exchange of the entire or parts of the prosthesis due to deep infection, and should be reported to the register immediately after surgery. The diagnosis of infection is made at the surgeon's discretion, based on pre- and perioperative assessment and evaluation, and is not to be corrected to the register based on peroperative bacterial cultures. Due to this lack of validation, the rate of revision for infection will only be an approximation of the true rate of periprosthetic joint infection (PJI). Our aim was to validate the reporting of infection after total hip arthroplasty, and to assess if revisions for infection actually represented true PJI. Methods. We investigated the reported revisions for infection and aseptic loosening after total hip arthroplasty from 12 hospitals, representing one region of the country, reported during the period 2010–2020. The electronic patient charts were investigated for information on surgical treatment, use of antibiotics, biochemistry and microbiology findings. PJI was defined as growth of at least two phenotypically identical microbes in perioperative tissue samples. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. Results. 145 revisions for infection and 137 revisions for aseptic loosening were reported. Of the reported infections, there were 141/145 true positives and 4/145 false positives. Of the reported aseptic loosenings, there were 126/137 true negatives and 11/137 false negatives. This gives a positive predictive value of 0.97, negative predictive value of 0.92, sensitivity of 0.93, specificity of 0.97 and accuracy of 0.95. Interpretation. We found the reporting revision for infection after total hip arthroplasty to the national register accurate. There was high correlation between reported revision for infection and PJI. Studies on revision for infection from arthroplasty registers may therefore be considered as reliable as studies of true PJI

Aim. Diagnosing periprosthetic joint infections (PJI) can be very challenging, especially infections caused by low virulence microorganisms. No single test with a 100% accuracy is available yet. Hence, different infection definitions were introduced to improve the diagnostic confidence and quality of research articles. Due to constant developments in this field, infection definitions are adopted continuously. The aim of our study was to find the most sensitive currently available infection definition among three currently used criteria (International Consensus Meeting – criteria 2018 (ICM), Infectious Diseases Society of America - criteria 2013 (IDSA), and European Bone and Joint Infection Society – criteria 2021 (EBJIS)) for the diagnosis of PJI. Method. Between 2015 and 2020, patients with an indicated revision surgery due to septic or aseptic failure after a total hip or knee replacement were included in this retrospective analysis of prospectively collected data. A standardized diagnostic workup was done in all patients. The components of the IDSA-, ICM-, and EBJIS- criteria for the diagnosis of PJI were identified in each patient. Results. Overall, 206 patients (hip: n=104 (50%); knee: n=102 (50%)) with a median age of 74 years (IQR 65 – 80y) were included. 101 patients (49%) were diagnosed with PJI when using the EBJIS- criteria. Based on the IDSA- and ICM- criteria, 99 patients (48%, IDSA) and 86 patients (42%, ICM) were classified as septic. Based on all three criteria, 84 cases (41%) had an infection. 15 septic cases (n=15/206; 7%) were only identified by the IDSA- and EBJIS- criteria. In 2 patients (n=2/206, 1%), an infection was present based on only the ICM and EBJIS criteria. No case was classified as infected by one infection definition alone. A statistically significant higher number of inconclusive cases was observed when the ICM criteria (n=30/206; 15%) were used in comparison to the EBJIS criteria (likely infections: n=16/206; 8%) (Fisher's exact test, p=0.041). The EBJIS definition showed a better preoperative performance in comparison to the other two definitions (p<0.0001). Conclusions. The most sensitive infection definition seems to be the novel EBJIS– criteria covering all infections diagnosed by the IDSA- and ICM-criteria without detecting any further infection. In addition, less inconclusive (infection likely) cases were detected by the EBJIS-criteria in comparison with the ICM-criteria reducing the so called ‘grey zone’ significantly which is of utmost importance in clinical routine

Background. Increasing evidence suggests a link between the bearing surface used in total hip arthroplasty (THA) and the occurrence of infection. It is postulated that polyethylene has immunomodulatory effects and may influence bacterial function and survival, thereby impacting the development of periprosthetic joint infection (PJI). This study aimed to investigate the association between polyethylene type and revision surgery for PJI in THA using data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). We hypothesized that the use of XLPE would demonstrate a statistically significant reduction in revision rates due to PJI compared to N-XLPE. Methods. Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) spanning September 1, 1999, to December 31, 2021, were used to compare the infection revision rates between THA using N-XLPE and XLPE. We calculated the Cumulative Percentage Revision rate (CPR) and Hazard Ratio (HR) while controlling for factors like age, sex, body mass index (BMI), American Society of Anesthesiologists’ (ASA) grade, and head size. Results. From the total 361,083 primary THAs, 26,827 used N-XLPE and 334,256 used XLPE. Excluding data from the first 6 months post-surgery, 220 revisions occurred in the N-XLPE group and 1,055 in the XLPE group for PJI. The HR for infection revision was significantly higher in N-XLPE compared to XLPE, at 1.64 (95% CI, 1.41–1.90, p<0.001). Conclusions. This analysis provides evidence of an association between N-XLPE and revision for infection in THA. We suspect that polyethylene wear particles contribute to the susceptibility of THA to PJI, resulting in a significantly higher risk of revision for infection in N-XLPE hips compared to those with XLPE. Level of Evidence. Therapeutic Level III

The incidence of PJI in knee replacements is 2.8% and slightly lower with hip replacement surgery. PJI make up 15% (or even more) of knee revisions. To combat PJI, antibiotic laden bone cement has been used for many decades, but antibiotic stewardship dictates more prudent management of antimicrobials. Projected increase in infection rate, due to increased surgery and latent infection to be almost 5-fold up to 2035. Biofilm is a complex structure of bacteria and polysaccharide matrix and, is recognised as a major component in PJI and other orthopaedic infections. Biofilm is responsible for high incidence of resistance to antimicrobials and ineffective host immune response. Method. Stabilized hypochlorous acid has been reported to have a rapid kill rate on all pathogens, including MDR pathogens associated with chronic and acute wound infections. It destroys biofilm on contact, is not cytotoxic, reduces inflammation and stimulates wound healing. 0,038% of Hypochlorous acid was used as prophylaxis against infection and to treat PJI. We report on our experience with hypochlorous acid as a wound irrigation as prophylaxis against infection (more than 600 cases) and for PJI. We also report on a University study where a head to head analysis was done on the anti-biofilm efficacy between hypochlorous acid 0,038% (Trifectiv Surgical Wound Irrigation) and Product X (an industry-standard product for the prevention and treatment of biofilm infection. Hypochlorous acid offers a valuable addition to the armamentarium of wound antiseptics, with added anti-inflammatory value. An in vitro study demonstrated superior efficacy against biofilm when compared to Product X