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

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

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. 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

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

To determine risk factors of infection in total knee arthroplasty. This descriptive study was conducted in the Department of Orthopedics for a duration of three years from January 2016 to January 2019. All patients undergoing primary total knee replacement were included in the study. Exclusion criteria were all patients operated in another hospital and revision total knee replacement. All patients were followed up at 2, 4, 8, 12 and 24 weeks post-operatively. Signs of inflammation and inflammatory markers such as total leukocyte count (TLC), C-reactive protein (CRP) and ESR were measured. Risk factors like age, body mass index (BMI), ASA, co-morbid conditions were also noted. A total of 78 patients underwent primary unilateral Total Knee Replacement (TKR) during the study period. Of these, 30 (34.09%) were male and 48 (61.54%) female patients. Mean age of patients was 68.32 ± 8.54 years. Average BMI 25.89 Kg/m2 .Osteoarthritis was the pre-dominant cause of total knee replacement (94.87%). Among co-morbid factors 33.33% were diabetic, 28.20% having ischemic heart disease and 12.82% with chronic lung disease. Upon anaesthesia fitness pre-operatively, 91.02% patients had an American society of anaesthesiologist score (ASA) between 0–2 while 07 (8.97%) between 3- 5. Average duration of surgery was 85.62± 4.11 minutes. 6.41% cases got infected. In majority of the infected cases (60%), Staphylococcus aureus was the infective organism. Diabetes Mellitus (p=0.01) and Obesity (p=0.02) had a significant relation to post-operative infection. Pre-operative risk evaluation and prevention strategies along with early recognition of infection and control can greatly reduce the risk of joint infection post-TKR which will not only improve the mobility of patient but also its morbidity and mortality as well. Key Words:. C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), Staphylococcus aureus, Total Knee Arthroplasty (TKA)

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

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)

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

Introduction. Accurate diagnosis of peri-prosthetic joint infection is critical to allow adequate treatment. Currently, the criteria of the Musculo-Skeletal Infection Society (MSIS) serve as a validated reference tool. More recently, these criteria have been modified for better accuracy. The goal of this study was to compare retrospectively the diagnostic accuracy of these two different tools in cases of known peri-prosthetic hip or knee infection or in aseptic cases and to analyze one additional criterion: presence of an early loosening (prior to 2 years after implantation). Material – Methods. All cases of hip or knee prosthesis exchange operated on at our department during the year 2017 have been selected. There were 130 cases in 127 patients: 67 men and 60 women, with a mean age of 69 years − 69 total hip (THA) and 61 total knee (TKA) arthroplasties. 74 cases were septic and 53 cases were aseptic. All criteria included in both classifications were collected: presence of a fistula, results of bacteriological samples, ESR and CRP levels, analysis of the joint fluid, histological analysis. Additionally, the presence of an early loosening was recorded. The diagnosis accuracy of the classical MSIS classification and of the 2018 modification were assessed and compared with a Chi-square test at a 0.05 level of significance. Results. The conventional MSIS classification correctly discriminated between infected and non-infected cases in 128/130 cases (98%). There were two failures by infected cases: one case was considered infected with no major criteria and only three minor criteria; one case was considered infected with no major criteria and only two minor criteria. There was no failure by non-infected cases. The new MSIS classification correctly discriminated between infected and non-infected cases in 129/130 cases (99%). There was one single failure by infected cases: one case was considered infected despite a score of 4 points. There was no significant difference between the diagnostic accuracy of both classifications. The presence of an early loosening had a high specificity (85%) but a low sensitivity (22%). Discussion. The conventional MSIS classification had a high diagnostic accuracy. The new MSIS classification offered only minor, non significant increase of this accuracy. As the new classification involves several additional biological assays, these results might question the cost-effectiveness of the new classification. The presence of an early loosening might be an interesting additional criterion at no additional cost

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

Aim. Previous publications have suggested that the incidence of revisions due to infection after THA is increasing. We performed updated time-trend analyses of risk and timing of revision due to infection after primary THAs in the Nordic countries during the period 2004–2018. Methods. 569,463 primary THAs reported to the Nordic Arthroplasty Register Association from 2004 through 2018 were studied. We estimated adjusted hazard ratios (aHR) with 95% confidence interval by Cox regression with the first revision due to infection after primary THA as endpoint. The risk of revision was investigated. In addition, we explored changes in the time span from primary THA to revision due to infection. Results. 5,653 (1.0%) were revised due to infection. The risk of revision due to infection increased through the study period. Compared to the period 2004–2008, the aHRs were 1.4 (95%CI 1.3–1.5) for 2009–2013, and 1.9 (1.7–2.0) for 2014–2018. We found an increased risk in all four Nordic countries. Compared to 2004–2008, the aHR due to infection 0–30 days after THA was 2.5 (2.1–2.9) for 2009–2013 and 3.4 (3.0–3.9) for 2013–2018. The aHR of revision due to infection 31–90 days after THA was 1.5 (1.3–1.9) for 2009–2013 and 2.5 (2.1–3.0) for 2013–2018, compared to 2004–2008. Beyond 91 days after THA, the risk of revision due to infection was stable over the whole study period. Interpretation. The risk of revision due to deep infection after THA nearly doubled throughout the period 2004–2018. This increase was mainly due to an increased risk of early revisions. The cause for these changes may be multifactorial (patient selection, diagnostics, revision strategy, completeness of reporting, etc.), are not possible to disclose in the present study, and warrants further research

Aim. Debridement, Antibiotics, Irrigation, and implant Retention (DAIR) is a surgical treatment protocol suitable for some patients with fracture related infection (FRI). Clinically relevant pre-clinical models of DAIR are scarce and none have been developed in large animals. Therefore, this project aimed to develop a large animal model for FRI including a DAIR approach and compare outcomes after 2 or 5 weeks of infection. Method. Swiss Alpine sheep (n=8), (2–6 years, 50–80 kg) were included in this study. This study was approved by cantonal Ethical authorities in Chur, Switzerland. A 2 mm osteotomy was created in the tibia and fixed with a 10-hole 5.5 mm steel plate. Subsequently, 2.5 mL of saline solution containing 10. 6. CFU/mL of Staphylococcus aureus MSSA (ATCC 25923) was added over the plate. Sheep were observed for 2 (n=3) or 5 weeks (n=5) until revision surgery, during which visibly infected or necrotic tissues were removed, and the wound flushed with saline. All samples were collected for bacterial quantification. After revision surgery, the sheep were treated systemically for 2 weeks with flucloxacillin and for 4 weeks with rifampicin and cotrimoxazole. After 2 further weeks off antibiotics, the animals were euthanized. Bacteriological culture was performed at the end of the study. Bone cores were isolated from the osteotomy site and processed for Giemsa & Eosin and Brown and Brenn staining. A radiographical examination was performed every second week. Results. Bacteriological evaluation of the retrieved samples during revision surgery showed no significant difference between the 2 vs 5 weeks infection periods in term of total CFU counts. At the end of the study, radiographical examination showed callus formation over the osteotomy site in both groups, although the osteotomy was not completely healed in either group. At euthanasia, the 2 weeks infection group showed a higher soft tissue burden compared to the 5 weeks group, whereby the infection in the 5 weeks group was primarily located in the bone and bone marrow. Conclusions. The large animal model of FRI and DAIR was successfully established. Bacteriological outcomes highlight that the increasing duration of the infection does not change the outcome but the location of the infection from a predominantly soft tissue infection to a deeper bone and intramedullary (IM) channel infection. The debridement of the IM channel could potentially reduce the infection burden by eliminating those bacteria not easily reached by systemic antibiotics, though is not practical using conventional techniques

Introduction. The management of fracture-related infection has undergone radical progress following the development of international guidelines. However, there is limited consideration to the realities of healthcare in low-resource environments due to a lack of available evidence in the literature from these settings. Initial antimicrobial suppression to support fracture union is frequently used in low- and middle-income countries despite the lack of published clinical evidence to support its practice. This study aimed to evaluate the outcomes following initial antimicrobial suppression to support fracture union in the management of fracture-related infection. Materials & Methods. A retrospective review of consecutive patients treated with initial antimicrobial suppression to support fracture healing followed by definitive eradication surgery to manage fracture-related infections following intramedullary fixation was performed. Indications for this approach were; a soft tissue envelope not requiring reconstructive surgery, radiographic evidence of stable fixation with adequate alignment, and progression towards fracture union. Results. This approach was associated with successful treatment in 51/55 (93%) patients. Fracture union was achieved in 52/55 (95%) patients with antimicrobial suppression alone. Remission of infection was achieved in 54/55 (98%) patients following definitive infection eradication surgery. Following antibiotic suppression, 6/46 (13%) pathogens isolated from intra-operative samples demonstrated multi-drug resistance. Conclusions. Initial antimicrobial suppression to support fracture healing followed by definitive infection eradication surgery was associated with successful treatment in 93% of patients. The likelihood of remission of infection increases when eradication surgery is performed in a healed bone. This approach was not associated with an increased risk of developing multi-drug-resistant infections compared to contemporary bone infection cohorts in the published literature