Aim. Treatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular polymeric substances (EPS) degradation depolymerases, conjugated with rifampicin-loaded liposomes (Lip-RIF@Phage) by bio-orthogonal functionalization strategy to target biofilm (Figure1). Method. Methicillin-resistant Staphylococcus aureus (MRSA) biofilm was grown on porous glass beads for 24 h in vitro. After the biofilm formation, beads were exposed to 0.9% saline, then sonication. Quantitative and qualitative biofilm analyses were performed by colony counting, scanning electron microscopy and isothermal microcalorimetry. A rat model of total knee arthroplasty infected with the bioluminescent MRSA strain was developed as the PJI model to evaluate the efficacy of Lip-RIF@Phage anti-biofilm therapy in vivo, then the creatinine, alanine transaminase, and aspartate transaminase values were evaluated throughout the entire treatment process. Results. After treatment with Lip-RIF@Phage, no bacterial colonies were observed, consistent with findings from scanning electron microscopy. Similarly, isothermal microcalorimetry revealed no detectable heat following Lip-RIF@Phage treatment, aligning with these observations. In vivo experiments demonstrated a significant reduction in biofilm cell load compared to all other tested conditions, with no evidence of systemic toxicity on renal and liver functions attributed to Lip-RIF@Phage. Conclusions. The innovative depolymerase-phagobot nanosystem (Lip-RIF@Phage) exhibits remarkable efficacy in completely eliminating biofilm cells in vitro. It serves as an excellent carrier for antibiotic delivery, enhancing antibiotic penetration through biofilms and improving biofilm eradication efficacy. Furthermore, it enables personalized treatment strategies against biofilm-associated multidrug-resistant (MDR) infections by maximizing the effectiveness of any remaining sensitive antibiotics. For any tables or figures, please contact the authors directly

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. Haematogenous prosthetic joint infections account for 20-35% of total prosthetic infections. Debridement, antibiotics and implant retention (DAIR) is a well-accepted treatment for these infections and probably the most desired by surgeons, since it tries to maintain a functional and stable implant. However, the risk of DAIR failure is not negligible and some risk factors have been described, and also, different scores, such as CRIME80. Nonetheless, less is known about the impact of positive blood cultures may have on DAIR treatment. The aim of our study is to analyze whether the presence of a positive culture is a risk factor for DAIR failure. Method. A retrospective cohort study of 50 late acute haematogenous TKA infections was performed from 2015 to 2023. DAIR failure was defined as the need of a subsequent intervention either a new DAIR or a revision surgery. So, patients were divided into two groups depending on the surgical outcome: successful (SG) vs failure (FG). Demographic variables including age, gender, affected side and body mass index were collected. Patient's comorbidities were also collected including chronic obstructive pulmonary disease (COPD), diabetes, rheumatoid arthritis (RA), cirrhosis and chronic renal failure, etc. Other variables, such as ones included in CRIME80 (C-reactive protein (CRP) >150mg/dl and polyethylene exchange), were also collected. Results. 30 patients had a successful DAIR outcome (60%). Age and sex do not act as risk factors [OR 0.7 (0.2-2.6) and OR 0.4 (0.1-1.3)]. Neither do COPD [OR 3.3 (0.5-2.0), p=0.2]; RA [OR 0.8 (0.2-3.1), p=0.7]; CRP value [3.2 (0.9-11.2), p=0.06]; and polyethylene exchange [OR 0.4 (0.1-2.5), p= 0.3]. Thirty-five blood cultures (70%) were obtained before surgery (20 SG and 15 FG). Nine of the obtained blood cultures were positive (25.7%), being 7 from FG (46.7%) [OR 7.6 (1.3-4.8), p=0.02]. A logistic regression was performed where positive blood cultures were the only significant variable to predict DAIR failure (OR 12, 95% CI 1.1−18, p=0.049), after adjusting for all CRIME80 variables. Skin and soft tissue origin was described in 5 of the nine positive blood cultures (55.6%). Cardiovascular system was the second most common spread (22.2%), and then followed by urogenital and digestive tract. The most common microorganism in FG was Staphylococcus aureus (57.1%) [OR 6.4 (0.2-18.0), p=0.2]. Conclusions. Positive blood cultures may be another risk factor for DAIR failure. This can be important in diagnosis and it may be taken into account in antibiotic and surgical treatment strategies

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

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.

Aim

Evaluate the metabolites composition of the synovial fluid from patients with PJI or aseptic failure of total knee arthroplasties.

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. 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

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. The SOLARIO trial is a randomised controlled non-inferiority trial of antibiotic strategy for bone and joint infection. SOLARIO compares short or long post-operative systemic antibiotic duration, for patients with confirmed infections, who had local antibiotics implanted and no infected metalwork retained when undergoing surgery. This analysis compared systemic antibiotic use in the short (intervention) and long (standard of care) arms of the trial, in the 12 months after index surgery. Method. Data was collected prospectively from study randomisation, within 7 days of index surgery. All systemic antibiotics prescribed for the index infection were recorded, from health records and patient recall, at randomisation, 6 weeks, 3-6 months and 12 months after study entry. Start and end dates for each antibiotic were recorded. Results. 251 patients were randomised to short systemic antibiotics (up to 7 post-operative days) and 249 patients, to long systemic antibiotics. 5 participants in the short group and 2 participants in the long group withdrew from study follow-up. Complete data for all systemic antibiotics taken in the 12 months following surgery, were available for 237 participants in the short group and 236 participants in the long group. 80 participants across both groups were noted as having deviated from their assigned treatment strategy. Both groups received empiric antibiotics, predominantly vancomycin and meropenem, for up to 7 days after surgery. Considering each prescribed antibiotic as a separate duration (even when administered concurrently), participants assigned to standard care received a mean of 74.9 antibiotic-days. Participants assigned to short systemic antibiotics received a mean of 27.5 antibiotic-days in the 12 months after surgery. The most commonly prescribed antibiotics in both treatment groups were vancomycin and meropenem: these antibiotics accounted for 7.1 days prescribed per participant in the long group, and 6.3 days in the short group (p=0.37). Reasons for post-randomisation antibiotic prescribing in the short treatment group included later planned surgery, identification of bacteria requiring additional systemic antibiotics, and treatment of superficial wound infections. WHO AWaRe classification ‘watch’ and ‘reserve’ group antibiotics, such as ciprofloxacin, rifampicin, vancomycin and meropenem, accounted for 39.4 antibiotic-days per long group participant, and 16.5 antibiotic-days per short group participant. Conclusions. Considering the combined duration of all systemic antibiotics prescribed over 12 months, including those co-administered, participants in the short arm of the SOLARIO trial received considerably fewer days of all antibiotic classes, and particularly those antibiotics restricted in the WHO AWaRe classification (2021)

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

Aims. Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH. Methods. This cross-sectional study was carried out according to the “STrengthening the Reporting of OBservational studies in Epidemiology” statement. Data on 19 variables were collected at a single timepoint from 250 patients with ONFH who were treated at our medical centre between July and December 2023 using validated instruments or, in the case of hip pain, a numerical rating scale. Factors associated with pain severity were identified using hierarchical multifactor linear regression. Results. Regression identified the following characteristics as independently associated with higher pain score, after adjustment for potential confounders: Association Research Circulation Osseous classification stage IIIa or IIIb, bone marrow oedema, grade 3 joint effusion, as well as higher scores on pain catastrophizing, anxiety, and central sensitization. The final model explained 69.7% of observed variance in pain scores, of which clinical and radiological factors explained 37%, while psychological and neurophysiological factors explained 24% and demographic factors explained 8.7%. Conclusion. Multidimensional characteristics jointly contribute to the severity of pain associated with ONFH. These findings highlight the need to comprehensively identify potential contributors to pain, and to personalize management and treatment accordingly. Cite this article: Bone Joint Res 2024;13(11):673–681

Aim. Efficacious antibiotic treatment is crucial for managing and preventing orthopedic infections due to their complexity and associated risk of treatment failure. Previous reviews on antibiotic target tissue concentrations have primarily focused on static measurements, which may not accurately reflect the dynamic pharmacokinetic/pharmacodynamic (PK/PD) changes encountered in clinical settings. This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings using dynamic sampling methods. Method. In accordance with PRISMA guidelines, a literature search was conducted with a scientific librarian's assistance. PubMed and Embase databases were systematically searched using relevant MeSH terms, entries, and keywords. English-published studies between 2004 and 2023 involving systemic antibiotic administration and dynamic measurements were included. 4467 titles were identified. After title and abstract screening, 77 eligible studies remained. Results. The studies covered clinical and pre-clinical studies on both healthy and infected tissue. Dynamic measurements were obtained from various tissues including bone, intervertebral discs, joints, muscles, and subcutaneous tissue. Microdialysis was the predominant sampling method (98.70%, 76/77). Antibiotics like cefuroxime, linezolid, and vancomycin were extensively studied. Fluoroquinolones, tetracyclines, and most beta-lactams typically presented good tissue penetration in relation to relevant PK/PD-targets. In contrast, glycopeptides, macrolides, and flucloxacillin exhibited poorer penetration. Conclusions. This review provides valuable insights of antibiotic distribution in orthopedically relevant target tissues and settings, which may help improve dosing recommendations and treatment outcomes. Our findings are limited to the investigated dosing regimens and administration methods and depend on the chosen PK/PD target. Many antibiotics still require further research to address the significant knowledge gaps, such as the lack of dynamic evaluations for certain antibiotic types and further investigation across various orthopedic settings and tissues

Aim. We prospectively evaluated four different microbiological tools for diagnostics of prosthetic joint infections (PJI), and assessed their impact on the categorization of infection according to EBJIS guidelines. We compared culture, in-house real-time mPCR for S. aureus, S. lugdunensis, S. hominis, S. epidermidis, S. capitis, S. haemolyticus, C. acnes (mPCR), broad-spectrum PCR (Molzym) with 16S rRNA V3-V4 amplicon Sanger sequencing (16S PCR), and 16S rRNA V3-V4 amplicon next-generation sequencing (16S NGS) on MiSeq (Ilumina). Methods. A total of 341 samples (sonication fluid, tissue biopsy, synovial fluid) were collected from 32 patients with suspected PJI who underwent 56 revision surgeries at the Orthopaedic Centre University Hospital Ljubljana, between 2022 and 2024. Samples were processed using standard protocols for routine culture, followed by DNA isolation using the MagnaPure24 (Roche). All samples were tested with mPCR, and an additional ≥4 samples from each revision (244 in total) were subjected to further metagenomic analysis. Culture results were considered positive if the same microorganism was detected in ≥2 samples, ≥50 CFU/ml were present in the sonication fluid, or ≥1 sample was positive for a more virulent microorganism or if the patient had received antibiotic treatment. Results. Each tool demonstrated high sensitivity for correct EBJIS categorization (100% culture and 16S NGS, 96.88% mPCR and 16S PCR). The highest specificity was observed with mPCR and 16S PCR (87.5%), while culture (79.17%) and NGS (37.5%) showed lower specificity. In 27% (15/56) of revisions, all microbiological tests were negative, although infection was confirmed with histology in one case, and four cases were classified as infection-likely based on clinical signs. In 20% (11/56) of cases, all microbiological tests were positive; in three cases a combination of other EBJIS criteria (without microbiology) categorized the episodes as infection-likely and one as infection-unlikely, emphasizing the importance of microbiological tests in diagnostic criteria. In 43% (24/56) of revisions categorized as infection-unlikely using a combination of other EBJIS criteria, five had positive culture, and three had positive mPCR and 16S PCR. Fifteen (62%) had positive 16S NGS, 12 due to a low number of reads, which may indicate low-grade infection or possible contamination. Conclusion. To date, no test can be established as the ultimate gold standard. The lack of interpretation criteria can result in low specificity of some methods, as the threshold is difficult to determine. A multidisciplinary approach with combination of microbiological tools is still considered the most efficient

Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

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. Fast and accurate identification of pathogens causing periprosthetic joint infections (PJI) is essential to initiate effective antimicrobial treatment. Culture-based approaches frequently yield false negative results, despite clear signs of infection. This may be due to the use of general growth media, which do not mimic the conditions at site of infection. Possible alternative approaches include DNA-based techniques, the use of in vivo-like media and isothermal microcalorimetry (ITC). We developed a synthetic synovial fluid (SSF) medium that closely resembles the in vivo microenvironment and allows to grow and study PJI pathogens in physiologically relevant conditions. In this study we investigated whether the use of ITC in combination with the SSF medium can improve accuracy and time to detection in the context of PJI. Methods. In this study, 120 synovial fluid samples were included, aspirated from patients with clinical signs of PJI. For these samples microbiology data (obtained in the clinical microbiology lab using standard procedures) and next generation sequencing (NGS) data, were available. The samples were incubated in the SSF medium at different oxygen levels (21% O. 2. , 3% O. 2. and 0% O. 2. ) for 10 days. Every 24h, the presence of growth was checked. From positive samples, cultures were purified on Columbia blood agar and identified using MALDI-TOF. In parallel, heat produced by metabolically active microorganisms present in the samples was measured using ITC (calScreener, Symcel), (96h at 37°C, in SSF, BHI and thioglycolate). From the resulting thermograms the ‘time to activity’ could be derived. The accuracy and time to detection were compared between the different detection methods. Results. So far, seven samples were investigated. Using conventional culture-based techniques only 14.3% of the samples resulted in positive cultures, whereas NGS indicated the presence of microorganisms in 57.1% of the samples (with 3/7 samples being polymicrobial). Strikingly, 100% of the samples resulted in positive cultures after incubation in the SSF medium, with time to detection varying from 1 to 9 days. MALDI-TOF revealed all samples to be polymicrobial after cultivation in SSF, identifying organisms not detected by conventional techniques or NGS. For the samples investigated so far, signals obtained with ITC were low, probably reflecting the low microbial load in the first set of samples. Conclusion. These initial results highlight the potential of the SSF medium as an alternative culture medium to detect microorganisms in PJI context. Further studies with additional samples are ongoing; in addition, the microcalorimetry workflow is being optimized

Aim. Decubitus ulcers are found in approximately 4.7% of hospitalized patients, with a higher prevalence (up to 30%) among those with spinal cord injuries. These ulcers are often associated with hip septic arthritis and/or osteomyelitis involving the femur. Girdlestone resection arthroplasty is a surgical technique used to remove affected proximal femur and acetabular tissues, resulting in a substantial defect. The vastus lateralis flap has been employed as an effective option for managing this dead space. The aim of this study was to evaluate the long-term outcomes of this procedure in a consecutive series of patients. Method. A retrospective single-center study was conducted from October 2012 to December 2022, involving 7 patients with spinal cord injuries affected by chronic severe septic hip arthritis and/or femoral head septic necrosis as a consequence of decubitus ulcers over trochanter area. All patients underwent treatment using a multidisciplinary approach by the same surgical team (orthopedic and plastic surgeons) along with infectious disease specialists. The treatment consisted of a one-stage procedure combining Girdlestone resection arthroplasty with unilateral vastus lateralis flap reconstruction, alongside targeted antibiotic therapy. Complications and postoperative outcomes were assessed and recorded. The mean follow-up period was 8 years (range 2-12). Results. Of the 7 patients, 5 were male and 2 were female, with a mean age of 50.3 years at the time of surgery. Minor wound dehiscence occurred in 28.6% of the flap sites, and 2 patients required additional revisional procedures—one for hematoma and the other for bleeding. There were no instances of flap failure, and complete wound healing was achieved in an average of 32 days (range 20-41), with the ability to load over the hip area. No cases of infection recurrence or relapse were observed. Conclusions. An aggressive surgical approach is strongly recommended for managing chronic hip septic arthritis or proximal femur osteomyelitis in patients with spinal cord injuries. A single-stage procedure combining Girdlestone resection arthroplasty with immediate vastus lateralis muscle flap reconstruction proves to be an effective strategy for dead space management and localized antibiotic delivery through the vastus muscle, giving reliable soft tissue coverage around the proximal femur to avoid the recurrence of pressure ulcers. The implementation of a standardized multidisciplinary protocol contributes significantly to the success of reconstruction efforts

Aim. Prosthetic joint infections (PJI) are a common reason for revisions in patients that underwent total arthroplasty of the hip (THA) or knee (TKA). Extensive antibiotic treatment follows while a clear understanding of target site concentrations is lacking. The aim is to investigate the target site concentrations, like bone and synovial tissue concentrations, which consequently may lead to an optimisation of the dosing regiments of cefuroxime of PJI patients suffering from pain and immobility. Dosing optimisation may lead to a reduced risk of (re-)infection and adverse effects like renal-insufficiency and therefore lower health-care costs. Method. Patients (n=26) with PJI of hip or knee undergoing a one- or two-stage revision treated with cefuroxime were included as part of the ASTERICS study. During implant removal two samples were collected 15-30 and 60-120 minutes after IV infusion of plasma, bone tissue and synovial tissue and one synovial fluid sample. Samples were analysed using a UltraPerformance Convergence Chromotography – quadruple mass spectrometry system (UPC. 2. -MS/MS). Bone tissue and synovial tissue were pulverized before analysis acquiring for bone tissue a homogenate of cortical and cancellous bone. Using nonlinear mixed effect modelling (NONMEM) a base model was developed to analyse the bone to plasma ratio of cefuroxime in osteomyelitis patients. Results. Mean bone concentrations (mg/L) of cefuroxime at 30-60 min after IV administration in the knee and hip are 21.29 (SD:11.86) and 19.06 (SD: 11.79) respectively and 8.23 (SD:4.90) and 9.67 (SD:9.75) respectively at 90-120 min after IV administration. The penetration of cefuroxime described by the bone:plasma ratio into knee and hip affected by osteomyelitis is 0.3 and 0.4 respectively within 1 hour and 0.1 for both joints within 2 hours. The results mentioned here were collected during knee operations without blood void conditions. Concentration data was used to develop a base pharmacokinetic model using NONMEM and was best described by a two-compartment model. Conclusions. Cefuroxime penetrates osteomyelitis affected bone tissue within the hour proving the usefulness of cefuroxime as prophylaxis of orthopaedic surgery and as treatment option for PJI. However, PK modelling and further simulations need to prove whether repeated cefuroxime dosing in this population is required to reach minimal inhibitory concentrations in target tissue

Aim. Periprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge. 1. Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods. 2. A novel, ultrathin, silica-based sol-gel technology is evaluated in this research as an anti-infective coating for orthopaedic prosthetic devices, providing local antibiotic release following surgery. Method. Reduction in clinically relevant microbial activity and biofilm reduction by antimicrobial sol-gel coatings, containing a selection of antibiotics, were assessed via disc diffusion and microdilution culture assays using the Calgary biofilm device. 3. Proliferation, morphology, collagen, and calcium production by primary bovine osteoblasts cultured upon antibiotic sol-gel surfaces were examined, and cytotoxicity evaluated using Alamar blue staining and lactate dehydrogenase assays. Concentrations of silica, calcium and phosphorus compounds within the cell layer cultured on sol-gel coatings and concentrations eluted into media, were quantified using ICP-OES. Furthermore, cellular phenotype was assessed using alkaline phosphatase activity with time in culture. Results. Low antibiotic concentrations within sol-gel had an inhibitory effect on clinically relevant biofilm growth, for example 0.8 mg ml. -1. tobramycin inhibited clinically isolated S. aureus (MRSA) growth with an 8-log reduction in viable colony forming units. There was no significant difference in metabolic activity between untreated and sol-gel exposed primary bovine osteoblasts in elution-based assays. Reduction (2-fold) in metabolic activity in direct contact assays after 48 hours exposure was likely to be due to increased osteoinduction, whereas no impact upon cell proliferation were observed (p=0.92 at 14 days culture). The morphology of primary osteoblasts was unaffected by culture on sol-gel coatings and collagen production was maintained. Calcium containing nodule production within bovine osteoblastic cells was increased 16-fold after 14 days culture upon sol-gel. Conclusions. The ultrathin sol-gel coating showed low cytotoxicity, strong biofilm reducing activity and antimicrobial activity, which was comparable to antibiotics alone, demonstrating that sol-gel delivery of antibiotics could provide local antimicrobial effects to inhibit PJI growth without the need for bone cement. Future work will develop and evaluate sol-gel performance in an ex vivo explant bone infection model which will reduce the need for animal experimentation