Aim. Antimicrobial peptides occur naturally in our intrinsic immune system. PLG0206 is a novel, engineered, 24-amino acid peptide which has broad-spectrum antimicrobial activity, including in biofilm and against multi-drug resistant pathogens (1,2). This is the first clinical study to evaluate the safety and tolerability of PLG0206 when administered via an irrigation solution in patients with periprosthetic joint infections (PJI) following total knee arthroplasty (TKA) during debridement, antibiotics, and implant retention (DAIR). Secondary objectives were to evaluate pharmacokinetics (PK), biomarkers and initial clinical efficacy at one year post-DAIR procedure. Method. This prospective, multicenter, open-label, interventional study assessed two dose levels of PLG0206. Fourteen patients underwent revision for PJI after TKA. At the end of debridement, they received a single intra-articular irrigation of PLG0206 into the wound cavity lasting 15 minutes at concentrations of 3 mg/mL (n=7) or 10 mg/mL (n=7). Patients received post-operative care and intravenous/oral antimicrobial therapy as per their institutional guidelines. Patients were monitored for safety and signs of relapse or persistent infection for 12 months post study drug administration and PK and blood biomarkers were assessed. Results. All patients completed their final study assessment at Day 365. Over the 1-year follow-up, only one recurrence (7%) was noted at Day 169 in the low-dose cohort. Following dosing, nine patients (64.3%) had limited systemic exposure; maximum plasma concentration occurred 1-hour post-administration and declined rapidly to undetectable levels by 24 hours following treatment in all patients. The incidence of drug related treatment-emergent adverse events (TEAEs) was low. Two patients, both in the higher dose cohort, experienced a transient drug related TEAE; one of hypertransaminasaemia and one of neuralgia. Both events were moderate in severity and resolved within two weeks of onset. Conclusions. A single 15-minute irrigation of PLG0206 into the wound cavity of patients undergoing a DAIR procedure for PJI following TKA, is safe and well tolerated by patients. This new antimicrobial peptide offers a promising therapeutic option in musculoskeletal infection. The initial clinical efficacy is encouraging but now needs to be investigated in a much larger clinical trial

Aim. An instrumented blood culture system automatically flags when growth within the culture medium has been detected (‘work in progress’), and subsequently when the organism has been identified. We explore using this data to switch patients to oral therapy within 72 hours post-surgery, reducing costs and improving antimicrobial stewardship. Method. This retrospective review focused on clinically significant culture-positive bone and joint infections over a 5-month period in 2022. Two cohorts were defined as either having positive intraoperative microbiology at <72 hours or at ≥72 hours. Results. 150 patients were included. 133/150(88%) exhibited microbial growth <72hours. Of these, 98/133(74%) had all organisms identified <72-hours, and 34/133(26%) had additional organisms ≥72 hours. 19/151(12%) patients had their first positive cultures ≥72hrs from sampling. The most common isolates identified within 72 hours were S. aureus(30%), Enterobacteriaceae (26%), and Coagulase-negative Staphylococcus (CoNS)(19%). If no growth was observed by 48 hours, there was a 69.6% probability that subsequent growth wouldn't occur; this probability increases to 81.9% by 72 hours, 88.7% by 96 hours, 91.0% by 120 hours, and 95.0% by 144 hours (see figure 1). The most common isolates identified ≥72 hours were CoNS(28%), Cutibacterium acnes(16%) and S. aureus(12%). Assessing oral antibiotic regimes for isolates identified after 72 hours demonstrated that linezolid would cover isolates from 96% of patients, tetracyclines 92% of patients, clindamycin 85% of patients, and ciprofloxacin and rifampicin would cover 80% of patients. Vancomycin and meropenem, our standard empirical therapy, gave the best cover at 96% of patients. Conclusions. This study suggests there is sufficient microbiological information at 72 hours for most patients to allow transition to a targeted regimen. If there has been no detection of growth when using an instrumented blood culture system by 72 hours, it is likely that there will be no growth. For any tables or figures, please contact the authors directly

Aim. Periprosthetic Joint Infection (PJI) is a devastating complication in hip and knee joint arthroplasty. The “JS BACH” classification system was developed in 2021 to stratify the complexity of PJI, and more importantly, to act as a tool to guide referrals to specialist centers. The “JS BACH” classification has not been validated in an external cohort. This study aimed to do so using a large prospective cohort from Australia and New Zealand. Method. We applied the JS-BACH classification to the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort. This prospective study of newly diagnosed PJI collected 2-year outcome data from 653 participants enrolled in 27 hospitals. The definition of PJI treatment failure at 24 months was any of the following: death, clinical or microbiological signs of infection, destination prosthesis removed, or ongoing antibiotic use. Results. Individual cases were classified as per JS-BACH into “1 - uncomplicated” (n = 268), “2 - complex” (n = 330), and “3 - limited options” (n = 55). This cohort was similar to the original JS-BACH population in terms of baseline characteristics. However, there was a difference in complexity, with more DAIR procedures, fewer revision procedures, and a higher proportion of uncomplicated patients in the PIANO cohort. The risk of treatment failure correlated strongly with the JS-BACH category, with odds ratios (95% CI [confidence interval]) for category 2 versus 1 of 1.75 (1.24 to 2.47) and for category 3 versus 1 of 7.12 (3.42 to 16.02). Conclusions. Despite the PIANO study population being less complicated than the original derivation cohort, the JS-BACH classification showed a clear association with treatment failure in this large external cohort

Background. Two-stage revision arthroplasty is the standard treatment for chronic hip and knee periprosthetic joint infections (PJI). Accurate diagnosis of persistent infections at 2nd stage using established biomarkers and diagnostic criteria is of paramount importance. This study aimed to evaluate the diagnostic value of synovial calprotectin and alpha-defensin, and compare established diagnostic criteria from the International Consensus Meeting (ICM 2018) and the European Bone and Joint Infection Society (EBJIS 2021) to determine persistent PJI at the 2nd stage of a two-stage revision arthroplasty. Methods. We retrospectively analyzed 97 patients who underwent 100 two-stage revisions (hip: 39, knee: 61). Synovial fluid samples were assessed for calprotectin and alpha-defensin levels. ICM 2018 and EBJIS 2021 were applied to all patients undergoing 2nd stage revision. Receiver operating characteristic (ROC) curves and Youden Index were utilized to determine optimal cut-off values, and correlations between biomarkers were evaluated. The microbiological spectrum was analyzed at 2nd stage and re-revision surgery. Results. Calprotectin levels showed a sensitivity of 66.7%, specificity of 32.9%, and accuracy of 38.0% in predicting septic failure. Alpha-defensin showed sensitivity of 28.6%, specificity of 87.8%, and accuracy of 79.2%. Significant correlations included: calprotectin with PMN% (r = 0.471, p = 0.05) and alpha-defensin with WBC (r = 0.830, p < 0.01) in the successful cohort. For septic re-revisions, calprotectin and alpha-defensin were highly correlated (r = 0.969, p < 0.01). ICM correctly diagnosed persistent PJI in 26.7%, while EBJIS diagnosed 24.2%. The microbial spectrum shifted from gram-positive to gram-negative bacteria between reimplantation and re-revision surgeries. Conclusion. Synovial calprotectin and alpha-defensin demonstrated limited accuracy in ruling out persistent PJI at reimplantation. The low sensitivity of current diagnostic criteria, combined with the observed shift in microbial spectrum, underscores the challenges in diagnosing persistent PJI during 2nd stage of a two-stage revisions arthroplasty

Aim. Arthroscopic interventions have revolutionized the treatment of joint pathologies. The appropriate diagnostics and treatment are required for infections after ligament reconstructions using non-resorbable material such as tendon grafts, anchors, and sutures, prone to biofilm formation. The infection rate is around 1% for knee and shoulder, while up to 4% for Achilles tendon reconstructions. Despite high number of these procedures worldwide, there is limited evidence about the best treatment protocol. Our study aimed to provide a general protocol for the treatment of small implants for soft tissue reconstruction. Method. Between 2019 and 2023, we treated 48 infections of ligament, meniscus, and tendon reconstructions out of 7291 related procedures performed in the same time period. Early infection (<30 days) were treated with an arthroscopic debridement and implant retention (DAIR), except Achilles tendons had open DAIR, while those with delayed or chronic infection (>30 days) were treated with extensive debridement and lavage combined with one-stage exchange (OSE) or implant removal. During surgery, at least 5 microbiological s and samples for histopathology were obtained. The removed material was sonicated. After surgery, all patients were one week on iv. antibiotics, followed by oral antibiofilm antibiotics for 6 weeks including rifampicin and/or a quinolone. All patients were followed for at least 1 year. Failure was defined as the need for additional revision surgery after finished iv. antibiotic treatment. Results. Among 48 patients, 38 were early and 10 were late acute or chronic infections. The incidence of infection for our cohort was 0.7%. We observed 27 infections after ligament reconstruction of the knee, 15 of the shoulder, 5 of the ankle, and 1 infection of the elbow joint. 40 patients were treated with DAIR, 5 with OSE, and 3 with implant removal. We had 11 C. acnes, 10 S. aureus, 6 S. epidermidis, 2 P. aeruginosa, 2 S. lugdunensis, 10 mixed flora, and 3 culture-negative infections. 12 patients received antibiotics before surgery, and all culture-negative infections were related to this subgroup. We observed 2 failures, both in a combination of proximal tibial osteotomy and ligament reconstruction of the knee joint. The success rate of our protocol was 96%. Conclusions. Prompt surgical treatment followed by 6 weeks of antibiotic treatment cured 96% of infections of small implants after reconstruction procedures of knee, shoulder, and ankle joints. Our study is the first to provide a treatment protocol for infections of small implants after ligament reconstruction procedures

Aim. This retrospective study evaluated the outcome of treatment for unhealed fracture-related infections (FRI). Methods. We identified a consecutive, single-centre cohort of patients having treatment for an FRI Consensus confirmed FRI. All fractures were unhealed at the time of treatment. Patients were followed up for at least one year. Successful outcome was a healed fracture without recurrent infection. Lack of union, persistent infection and/or unplanned reoperation defined failure. Results. Demographics: 183 patients (184 FRIs) with mean age 52.1 years (range 17-96) were treated and followed up for a mean of 2.8 years (range 1-9.4). Mean duration of FRI was 1.1 years with 65 (35.5 %) presenting within 6 months of injury. 118 patients had established infected non-union. FRI was most frequent in the tibia (74), femur (48) and humerus (24). 171 patients were BACH Complex. 75.5% of FRIs were culture positive, with Staph. aureus being the most frequent organism. Polymicrobial infection and Gram negative cultures were common (25.5% and 33.6%). Treatment: 98.3% of surgeries were performed in one stage with just 3 planned 2-stage procedures (2 endoprosthetic replacements and 1 free fibular flap). No bone graft was used in any surgery and all wounds were closed at first operation. 48 cases (26%) required flap coverage (29 free flaps and 19 local flaps). Local antibiotics were used in 124 cases (67.4%) of primary surgeries. All patients had sampling, debridement, systemic antibiotics and wound closure. 40 (21.7%) had DAIR, 31 (16.8%) had new internal fixation and 105 (57.1%) had external fixation (including 79 Ilizarov fixators). Outcomes: After primary surgery, 84.6% of all patients were infection-free and 77.2% had united. After further surgery, 98.8% were infection-free and 98.1% had united. External fixation techniques achieved infection eradication in 89.1% compared to 71.7% with any internal fixation (p=0.005). Primary internal fixation achieved union in 81.7% compared to 74.3% with external fixation (p=0.27). Secondary surgery after external fixation was mainly docking site fixation. Conclusion. Unhealed FRIs present a difficult challenge for treatment. This large series demonstrated that single-stage treatment, without bone grafting, gave acceptable results with few reoperations. Primary external fixation gave more certainty of infection eradication but required more reoperations to secure union. However, this difference in reoperation was not statistically significant. We strongly advocate managing these patients with a multidisciplinary team which can treat all aspects of the condition

Aim. Successful management of native Joint septic arthritis (SA) hinges on the timely initiation of appropriate antibiotic therapy coupled with thorough joint debridement. Since 2018 we have implemented a protocol for empirical antibiotic in patients with suspected SA recommending amoxicillin/clavulanate (and cotrimoxazole in cases of beta-lactams allergy) based on local flora. Nevertheless we have recently found that institutional compliance to the protocol is only about 50% and many physicians are still choosing alternative wider spectrum regimens. The aim of this study is to assess whether current clinical and epidemiological characteristics of patients treated for this condition justify an update or whether previous recommendations are still valid. Method. All adult patients admitted to our institution with suspected SA between 2018-2022 were retrospectively reviewed. Data was collected from electronic medical records and then compared to similar data previously collected concerning the 2009-2017 period (that served as a basis for the aforementioned protocol). Results. A summary of available data from both time periods can be found in table 1. Overall, among the 35 patients with positive microbiology treated between 2018-2022, amoxicillin/clavulanate is appropriate for 30 (86%) of isolates (vs 88% in historic control). Analysing the whole cohort, we found that previous contact with healthcare services (hospital admission or prolonged ER stay) (p=0.0044) and antibiotic treatment for any infection (p= 0.0213) in the previous six months correlate with resistance to amoxicillin/clavulanate. In these patients, the proposed alternative cotrimoxazole is effective in 77% of cases. Conclusions. The institutional guideline for empirical antibiotic therapy in native joint SA remains adequate and there seems to be no justification to deviate from protocol except in cases of patients admitted to the hospital or antibiotic treatment in the previous six months. In these cases methicillin-resistance coverage is probably appropriate. Pseudomonal coverage is seldom required in SA. For any tables or figures, please contact the authors directly

Aim. Daptomycin plus fosfomycin combination therapy is a valuable strategy for treating staphylococcal osteoarticular infections. Considernig that each gram of fosfomycin contains 330 mg of sodium, electrolytic imbalance due to sodium overload could pose safety issues, especially in the cardiopatic patients and/or in the frail elderly. The aim of this study was to compare the efficacy of using reduced vs. standard daily dose fosfomycin in combination with daptomycin in a cohort of patients with osteoarticular infections. Method. This analysis included adult patients with osteoarticular infections admitted to the Infectious Diseases Unit of our University hospital in the period Nov 2022 – Feb 2024 and who were treated with daptomycin (8-10 mg/kg/daily) plus 24h-continuous infusion (CI) fosfomycin at the standard-dose of 16 g daily (standard-dose group) or at the reduced-dose of 8-12 g daily (reduced-dose group). All the patients underwent therapeutic drug monitoring (TDM) of fosfomycin for granting a pharmacodynamic target attainment of 24h-area under the concentration-time curve over minimum inhibitory concentration (AUC24h/MIC) >95 against Staphylococcus aureus with an MIC value up to 32 mg/L and of 70%t>MIC. Estimated glomerular filtration rate (eGFR) was assessed at each TDM session. Patient clinical outcome was assessed. Results. The standard- and the reduced-dose groups included 43 (29 males, 67.4%) and 21 (11 males, 52.4%) patients, respectively. No differences in median age (54 vs. 63 years, p=36), weight (80 vs. 76 kg, p=0.13) and type of diagnosis [prosthetic joint infections (16 vs. 29, p=0.38), osteomyelitis (2 vs. 9, p=0.72), septic arthritis (3 vs. 3, p=0.39) and spondilodiscitis (0 vs. 2, p=1.0)] were observed between the two groups. Median eGFR was similar in the standard vs. the reduced-dose group (109 vs. 98 mL/min/1.73m2, p=0.004). In the reduced-dose group, CI fosfomycin was administerd at 8 and 12 g/daily in 12 and 9 patients, respectively. There was no difference between the standard- and reduced-dose groups in attainment of the pharmacodynamic targets of AUC24h/MIC>95 (41/43 vs. 20/21, p=1.0), of 70%t>MIC (43/43 vs. 21/21 p=1.0) and of clinical cure (39/43 vs. 19/21, p=1.0). Conclusions. Combination therapy of 8-10 mg/kg/daily daptomycin plus 8-12 g/daily CI fosfomycin may be as effective as that of 8-10 mg/kg/daily daptomycin plus 16 g/daily CI fosfomycin. The fosfomycin reduced-dose strategy allows to decrease the daily sodium load by 25-50% compared to the standard dose, thus reducing the risk of cardiac adverse events. TDM may be a valuable strategy for individualizing fosfomycin dose in patients with osteoarticular infections

Aim. Periprosthetic joint infection (PJI) and periprosthetic fracture (PF) are one of the most devastating complications in arthroplasty. Each complication by itself is challenging to solve. Yet, simultaneously, both complications are inconceivably complex to deal with, while the treatment regimen of PJI and PF are contradictory. Chronic PJI most often requires implant removal, while PF requires stability, regularly achieved by stable osteosynthesis. This study aims to (1) analyse the success rate of PJI with following concomitant PF during the treatment course in total hip arthroplasties (THA) and (2) to determine the risk factors for reinfection and subsequent revision surgery after treatment of PJI and PF. Method. This restrospective study analyzed 41 patients with concomitant PJI and PF during the PJI treatment period from 2013 to 2022 involving THA. Patients were divided in two cohorts termed success and failure and were statistically compared. The median follow-up time was 66 months (>12 months). All patients were considered individually and treated according to their individual needs in fracture and infection treatment. Re-arthroplasty survival was analyzed using the Kaplan-Meier method. Relevant risk factors were analyzed using the Mann-Whitney test or Chi-square, depending on the variable's scale. Results. The overall success rate of our cohort was 70,7%. Twelve patients required re-operation due to reinfection, resulting in a cumulative 12-month-reinfection rate of 19,5%. The estimated cumulative reinfection free survival rate was 68,3%. Significance in risk factors for failure were found in pathogen virulence grade, Difficult to treat pathogen and number of debridement during interval. On average the Harris Hip score was 66 in the group of reinfection compared to 77 in the group of success. Conclusions. Reoperation and re-infection rate remains high in patients with simultaneous PJI and PF in THA. Due to the heterogeneity of the fractures, soft tissue conditions and pathogens found, treatment must be individualised to salvage the limb. However, small cohorts impact the statistical strength negatively due to instances of two rare complications

Aim. Periprosthetic joint infection (PJI) is one of the most serious and frequent complications in prosthetic surgery. Despite significant improvements in the criteria for diagnosis of PJI, the diagnostic workflow remains complex and, sometimes, inconclusive. Host immune factors hold great potential as diagnostic biomarkers in bone and joint infections. We have recently reported that the synovial concentration of the humoral pattern recognition molecule long pentraxin 3 (PTX3) is a sensitive and specific marker of PJI in total hip and knee arthroplasty patients (THA and TKA) undergoing revision surgery [1]. However, the contribution to risk and diagnosis of PJI of the genetic variation in PTX3 and inflammatory genes that are known to affect its expression (IL-1b, IL-6, IL-10, and IL-17A) has not been addressed. Therefore, we assessed these relationships in a cohort of THA and TKA patients who underwent prosthesis revision by focusing on a panel of single nucleotide polymorphisms (SNPs) in the PTX3, IL-1β, IL-6, IL-10 and IL-17A genes. Method. A case-control retrospective study was conducted on an historic cohort of patients that received THA or TKA revision and were diagnosed with PJI (cases) or aseptic complications (controls) [1]. Samples of saliva were collected from 93 subjects and used for extraction of genomic DNA to perform genotyping of the PTX3, IL-1β, IL-6, IL-10 and IL-17A polymorphisms. Moreover, whenever available, samples of synovial fluid and plasma [1] were used to measure the concentration of the IL-1β, IL-10, and IL-6 proteins by immunoassay. Uni-and multivariate analyses were performed to evaluate the relationships between genetic, biochemical, and clinical variables. Results. The rs3024491 (IL-10) and rs2853550 (IL-1b) SNPs were found to be strongly associated with the risk of PJI. The synovial levels of PTX3, IL-1β, IL-10, and IL-6 were higher in cases than in controls, and a clear correlation emerged between the synovial concentration of PTX3 and IL-1b in cases only. Also, we identified a causal relationship between rs2853550, synovial concentration of IL-1b and that of PTX3 (that is induced by IL-1b). Conclusions. Our findings suggest that SNPs in the IL-10 and IL-1b genes could be used for early identification of THA and TKA patients with high risk of PJI. It is therefore conceivable that integrating genetic data into current diagnostic criteria would improve diagnosis of PJI

Aim. There is limited data on the frequency and impact of untoward events such as glove perforation, contamination of the surgical field (drape perforation, laceration, detachment), the unsterile object in the surgical field (hair, sweat droplet…), defecation, elevated air temperature…that may happen in the operating theatre. These events should influence the surgical site infection rate but it is not clear to what extent. We wanted to calculate the frequency and measure the impact of these events on the infection and general revision rate. Method. In our institution, scrub nurses prospectively and diligently record untoward events in the theatres. We have an institutional implant registry with close to 100% data completion since 2001, and surgeons register complications before discharge. We analysed the respective databases and compared the revision and infection rate in the group with untoward events with the outcome of all arthroplasty patients within the same period. Two-tailed Z statistical test was used for analysis. Results. Between 1.1.2012 and 31.12.2018 we operated 13574 prosthetic joints: 6232 primary THR (total hip replacement) and 5466 primary KR (total and partial knee replacement) and 1245 and 631 revisions respectively. During this period, we recorded 372 events (2.74%) including 20 (0.15 %) defecations, 40 (0.29 %) unsterile object in the surgical field, 73 (0.54%) field sterility violations, 45 (0.33 %) glove perforations, 45 (0.33 %) occasions with elevated air temperature, 106 (0.78%) with guests in the OR, 11 (0.08%) with wound near the surgical field, and 32 (0.24%) with other events. We followed the patients till 1.1.2022, in this time we recorded 27 (7.26%) reoperations in the cohort with untoward events. There were 9 (2.42%) infections and 18 (4.84%) aseptic revisions in the group with unwanted events. The infection rate for all TJR (total joint replacement) from the period 2012-2018, followed till 1.1.2022 was 2.23%, the revision rate for any reason was 4.37%. For all THR (primary and revision) the infection rate was 0.84%, the overall revision rate was 3.18% and for the KR (primary and revision) 1.71% and 5,82% respectively. The difference is significant at p>0.05 for infection rate. Conclusions. The potentially serious sterility disruptive events in the operative rooms did result in an increased infection rate but not an increase in revision rate. There is no data about the rate and the impact of these events besides for perforated surgical gloves with higher reported incidences than in our study influencing infection rate if perioperative antibiotic prophylaxis was not used. Ours is the first study reporting the impact of these unwanted events in the operating theatre. Key words. orthopaedic surgery, unwanted events, revision rate

Aim. Accurate diagnosis is key in correctly managing prosthetic joint infection(PJI). Shoulder PJI definition and diagnosis is challenging. Current PJI definitions, based overwhelmingly in hip/knee research, may not accurately diagnose shoulder PJI. Our aim is to compare the preoperative performance of two PJI definitions comparing it to definitive postoperative classification. Method. This is a retrospective study of patients who have undergone total shoulder revision surgery for infection between 2005 and 2022. Cases were classified using two different PJI definitions: a)the European Bone and Joint Infection Society (EBJIS) and; 2)the 2018 International Consensus Meeting(ICM) PJI specific shoulder definition. Preoperative classification was based on clinical features, inflammatory markers and synovial fluid leukocyte count and definitive classification also considered microbiology and histology results. Results. Preoperative and definitive PJI classification status of the 21 patients included were evaluated and is summarized in table 1. The shoulder specific 2018 ICM definition showed the highest agreement between preoperative and definitive classification (76.2%, k=0.153, p=0.006) compared to EBJIS (52.4%, k=0.205, p=0.006). In all cases, the classification was changed because of positive intraoperative microbiology (at least two identical isolates). Microbiology findings showed coagulase negative staphylococci, Staphyloccocus aureus and Cutibacterium acnes to be the most frequent. Four patients had polymicrobial infections. Conclusions. Both the EBJIS 2021 and 2018 ICM definitions have low accuracy in predicting shoulder PJI preoperatively. Clearly further studies with larger cohorts are in dire need focusing specifically on shoulder revision arthroplasty to improve on existing definitions. Caution is advised while extrapolating of criteria/thresholds recommended for hip/knee joints. For any tables or figures, please contact the authors directly

Aim. Predicting success of a Debridement, Antibiotics and Implant Retention (DAIR) procedure for Periprosthetic Joint Infection (PJI) remains a challenge. A failed DAIR might adversely affect the outcome of any future revision surgery for PJI. Hence, the ability to identify and optimise factors predictive of DAIR success would help target the procedure to the appropriate patient cohort and avoid unnecessary surgery for patients where a DAIR is unlikely to eradicate infection. Method. A retrospective review of our prospective Bone Infection Group database was performed to identify all patients who underwent a DAIR of their hip or knee arthroplasty. Diagnosis of PJI was confirmed using the Musculoskeletal Infection Society (MSIS) 2013 and the European Bone and Joint Infection Society (EBJIS) 2021 classification systems. DAIR surgery was grouped into “successful” or “unsuccessful” outcomes as per the MSIS working group outcome-reporting tool. Results. Sixty-Four consecutive patients with an acute PJI underwent a DAIR procedure between 2009 and 2020. Treatment was successful in 44 (69%). The chance of a successful DAIR was significantly greater if performed within one week of symptom onset compared to greater than one week duration (adjusted odds ratio (OR 0.11; p=0.027; 95% CI [0.02- 0.78]). The chances of a successful DAIR was not influenced by whether the surgeon was an arthroplasty or non-arthroplasty surgeon (OR 0.28; p=0.13; 95% CI [0.05- 1.48]). Isolated Streptococcus infection had a success rate of 100%; followed by Coagulasenegative Staphylococci 71% and Methicillin-susceptible Staphylococcus Aureus 65%. Polymicrobial infection had the worst outcome with a success rate of 47%. Conclusions. In our experience DAIR surgery performed within one week of symptom onset, significantly increased chances of successful infection eradication. Collaborative work is required to ensure arthroplasty patients access prompt appropriate surgical decision-making, remove barriers to early assessment and minimise delays to surgery

Aim. Determine therapeutic and prognostic value of three different prosthetic joint infections (PJI) staging systems – JS-Bach, McPherson and PJI-TNM. Method. Retrospective analysis of patients who received surgery for PJI between 2011 and 2022 at one single institution, including DAIR, 1-stage revision and 2-stage revision. We applied three staging systems - JS-Bach, McPherson, PJI-TNM – and categorize the results into A (less severe), B (intermediate) and C (most severe). Demographic data and comorbidities, anatomic location, type of treatment, recurrency of infection, final outcome and antibiogram were analyzed. Results. 186 patients were included, 112 (60%) were woman. Median age was 70 years old. 51% were submitted to DAIR, 10% to 1-stage revision and 39% to 2-stage revision. Recurrence of infection was found on 27% of patients after initial treatment. 10% died with complication related to PJI. Final status at last follow-up showed 96% of cases were ultimately free of infection at last follow-up. JS-BACH was associated with recurrence. All three staging systems were associated with final outcome. Conclusions. Despite all existing knowledge around risk factors for treatment failure of PJI, there is still a lack of a generally accepted classification system to accurately predict patient outcome. JS-BACH, McPherson and PJI-TNM are three different proposed classifications developed to predict clinical outcomes. To the best of our knowledge there are no studies directly comparing their performance. We retrospectively evaluated our cohort and found that all three correlated with final patient outcome but JS-BACH was the only who significantly correlated with infection recurrence after initial treatment

Aim. Swedish guidelines on antibiotic prophylaxis in arthroplasty surgery recommend cloxacillin in fixed doses that pay little attention to the patient's renal function and weight. Nevertheless, there are no studies on whether the resulting free prophylactic cloxacillin in vivo concentrations are optimal. We aimed to evaluate whether the current recommended prophylactic dosage of cloxacillin is adequate. Method. We performed a prospective two-centre study, measuring the free (active) cloxacillin concentrations in plasma throughout surgery, in patients subject to primary hip and knee prosthetic joint replacements, aiming at 100 patients per centre. To account for plasma-bone exposure differences, concentrations were considered adequate if twice the epidemiological cut-off value for cloxacillin concerning wild type Staphylococcus aureus whereas two-three times were labelled threshold values. The two enrolling hospitals are acute care hospitals in central Sweden, also performing 600 - 1200 primary hip and knee joint arthroplasties annually. All patients scheduled for elective primary hip or knee replacements from January 2022 to April 2024 were eligible for participation. Exclusion criteria were allergy towards penicillins, cognitive disorders leading to inability to sign informed consent, and an absence of interpreter in case of a patient not speaking Swedish or English. Results. We present results from the first 49 patients included. Four patients had free cloxacillin concentrations below cut-off (8.2%). These four cases had prolonged surgeries of 77-100 minutes. An additional 5/49 (10.2%) had threshold values. Conversely 5/49 (10.2%) cases had concentrations exceeding 15 times the needed. No cases with threshold or low cloxacillin concentrations were attributable to a lack of concerning timing and dosing of cloxacillin. All concentrations were above or equal to our cut-off at the start of surgery. Eighteen percent of patients were of normal of weight (BMI 18.5- 25). Of the rest 4% were morbidly obese (BMI >40), 41% obese (BMI 30-40) and 37% overweight (BMI 25-30). Twenty seven percent (43/159) had diabetes and 45% suffered cardiac disease. Conclusions. Some patients in our cohort had insufficient active cloxacillin levels at the end of prosthetic joint surgery. Previous studies indicate that insufficient prophylactic antibiotic concentrations might lead to an enhanced risk of prosthetic joint infections. Other patients were massively overdosed, leading to unnecessary ecological effects and potentially adverse reactions. As inadequate cloxacillin concentrations were not associated with a lack of compliance to current guidelines a change in practise might be needed. Our final results may help to determine how dosing should be adjusted

Aim. Megaprosthesis have become a standard option in limb preserving surgery after bone resection in musculoskeletal tumors. Recently they have also been used in complex revision arthroplasty in cases with massive bone loss. The aim of this study was to analyze the incidence of periprosthetic joint infection (PJI) both in primary oncology cases and aseptic revision cases and analyze which are the significant risk factors for PJI with a special interest on the use of prophylactic antibiotic loaded calcium sulfate beads. Method. All patients undergoing surgery with the use of megaprosthesis in our institution between January/2012 and December/2022 were retrospectively reviewed. Data was collected from electronic medical records. We identified 108 procedures involving megaprosthesis in 90 patients with an average follow-up of 37 months. Indications were 79 primary musculoskeletal tumors and 29 aseptic complex revision arthroplasty. Results. Table 1 shows relevant clinical information. No significant risk factor was found either in uni or multivariate analysis. PJI rate was 15% (12/79) for primary musculoskeletal surgery and 31% (9/29) for complex revision surgery. The use of antibiotic loaded calcium sulfate beads did not show an advantage – 22% (9/41) with vs. 18% (12/67) without. Conclusions. In this relatively small series it was not possible to show a significal association between PJI and certain known risk factors such as gender, ASA score, site of surgery (knee) and revision surgery. The use of antibiotic loaded calcium sulfate beads as prophylaxis was not beneficial in reducing PJI rates in our cohort. We acknowledge the limitations of our study: a small sample group, in a single institution with heterogeneity in terms of diagnosis and surgical site. We recognize the need for a multicentric study with a larger cohort to validate these findings. For any tables or figures, please contact the authors directly

Introduction. In recent years, many studies demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopaedic related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking. Material and Methods. We conducted a retrospective observational multicenter study in patients diagnosed with an early postoperative PJI (i.e less than 3 months after the index arthroplasty) treated with debridement, antibiotics and implant retention (DAIR). Patients from Europe and the USA were included. These two cohorts served as a quasi-randomised trial since an early oral antibiotic switch is routine practice in Europe versus a long duration of intravenous (IV) antibiotic treatment in the USA. Failure was defined as the clinical need for: i) a second DAIR, ii) implant removal, iii) suppressive antibiotic treatment or iv) infection related death. Results. A total of 668 patients were included. 277 received IV antibiotics for <14 days, 232 were given IV antibiotics between 14 - 27 days and 159 received IV antibiotics for >27 days. The overall 1-year failure rate within the 3 groups was 41.5%, 44.4% and 42.1%, respectively (P 0.80), and mainly comprised the need for a second DAIR. The results did not change when analyzing patients with or without obesity, the causative microorganism or the type of oral antibiotics. Conclusion. In early postoperative PJIs, a longer duration of IV antibiotic treatment is not associated with a lower failure rate of a DAIR procedure

Aim. As the number of performed total hip arthroplasties (THA) and total knee arthroplasties (TKA) has increased over the years, revision surgeries are expected to increase as well. Revision surgeries are associated with a longer operating room time, prolonged length of stay (LOS), and more frequent complications. Postoperative hematomas are a major reason for wound healing disturbances and periprosthetic joint infections (PJI). We aimed to systematically assess the use and safety of a microporous polysaccharide hemosphere (MPH) in revision THA and TKA. We focused on the risk reduction of further revision surgeries in case of wound healing disorders and hematoma, transfusion of packed red blood cells (PRBC), loss of hemoglobin (hb) and mean LOS following the use of MPH. Method. Our prospective study includes 89 patients who underwent revision surgery after THA and TKA with application of MPH and were compared to 102 patients who did not receive MPH and underwent revision surgery after THA and TKA. Five grams of MPH. 1. were applied periarticular before fascia closure and to the subcutaneous soft tissue. The follow-up was conducted in daily clinical visits during the inpatient stay and three months postoperatively in our outpatient clinic. Repeated revision surgery was performed in case of prolonged secretion (>10 days) or clinical suspicion of infection. After matching the cohorts the outcomes were statistically analyzed using paired methods. Results. A significantly lower odds ratio for repeat revisions was found for the MPH cohort (OR=0.312; 95%-CI 0.090, 0.893; p=0.027). Differences between pre- and postoperative hb levels, LOS and transfusions of PRBC did not reach significance. No intra- or postoperative complications to MPH occurred. Moreover, no infection relapse occurred after applying MPH. Conclusions. Routine use of MPH in revision arthroplasty management after TKA and THA appears to be safe and an effective way to support hemostasis, with no observed adverse events related to MPH use. There were noticeably less hematomas and revision surgeries in the MPH group. 1. Arista BD, Franklin Lakes, NJ, USA

Aim. This study aimed to externally validate promising preoperative PJI prediction models in a recent, multinational European cohort. Method. Three preoperative PJI prediction models (by Tan et al., Del Toro et al., and Bülow et al.) which previously demonstrated high levels of accuracy were selected for validation. A multicenter retrospective observational analysis was performed of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) between January 2020 and December 2021 and treated at centers in the Netherlands, Portugal, and Spain. Patient characteristics were compared between our cohort and those used to develop the prediction models. Model performance was assessed through discrimination and calibration. Results. A total of 2684 patients were included of whom 60 developed a PJI (2.2%). Our patient cohort differed from the models’ original cohorts in terms of demographic variables, procedural variables, and the prevalence of comorbidities. The c-statistics for the Tan, Del Toro, and Bülow models were 0.72, 0.69, and 0.72 respectively. Calibration was reasonable, but precise percentage estimates for PJI risk were most accurate for predicted risks up to 3-4%; the Tan model overestimated risks above 4%, while the Del Toro model underestimated risks above 3%. Conclusions. In this multinational cohort study, the Tan, Del Toro, and Bülow PJI prediction models were found to be externally valid for classifying high risk patients for developing a PJI. These models hold promise for clinical application to enhance preoperative patient counseling and targeted prevention strategies. Keywords. Periprosthetic Joint Infection (PJI), High Risk Groups, Prediction Models, Validation, Infection Prevention

Aim. Debridement, antibiotics and implant retention (DAIR) is recommended for acute postoperative and late acute prosthetic joint infection (PJI). There are two recommend scores to predict its outcome, KLIC and CRIME 80 scores respectively. They have not been widely adopted for decision making. We aim to evaluate them in predicting DAIR failure in our cohort. Method. All patients submitted to DAIR after total hip or knee PJI, between 2010 and 2021, with a minimum one-year follow-up, were retrospectively evaluated. We excluded tumoral total joint replacements. KLIC score was applied to acute PJIs and CRIME 80 to late acute (LA) PJI. LA PJI was defined as the development of acute symptoms occurring ≥ 3 months after implantation. Repeat DAIR was performed as needed. Failure was defined as the need for implant removal, amputation, infection related death and suppressive antibiotic therapy. Results. We included 102 patients. The overall failure rate was 35.5% (36/102). There was no significant difference for the rate of failure in patients that had one DAIR and those who repeated DAIR - 32.5% (26/80) vs. 45.5% (10/22) (p=0.26). There were no significant correlations between KLIC or CRIME 80 scores and failure rates (p=0.54 and p=0.93 respectively, figure 1). Focusing specifically on the cohort who underwent repeat DAIR (n=22), KLIC and CRIME-80 score were also not associated with failure (p= 0.44 and p=0.50 respectively, figure 1). No host, pathogen or antibiotic treatment related factors were found to predict failure. Conclusions. In our cohort KLIC- and CRIME-80 scores failed to be predictive of DAIR failure, even in the cohort that needed repeat DAIR. We were unable to find any independent failure risk factors. For any tables or figures, please contact the authors directly