Aims. Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods. We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli. Results. After immunity training, the levels of pro-inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interleukin (IL)-17A) and chemokines (CCL5, CXCL4, CXCL5, CXCL7, CXCL12) increased significantly in platelet releasate, while the levels of anti-inflammatory cytokines (IL-4, IL-13) decreased. Other platelet-secreted factors (e.g. platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, cathepsin D, serotonin, and histamine) were statistically indistinguishable between the two groups. Transfusion of platelets from trained mice into naïve mice reduced infection risk and bacterial burden after local or systemic challenge with either S. aureus or E. coli. Conclusion. Immunity training altered platelet releasate by increasing the levels of inflammatory cytokines/chemokines and decreasing the levels of anti-inflammatory cytokines. Transfusion of platelets from immunity-trained mice conferred protection against bone and joint infection, suggesting that alteration of platelet releasate might be an important mechanism underlying trained immunity and may have clinical implications. Cite this article: Bone Joint Res 2022;11(2):73–81

Aims. Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections. Methods. Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30). Results. Overall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union. Conclusion. Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications. Cite this article: Bone Jt Open 2023;4(7):516–522

Acute bone and joint infections in children are serious, and misdiagnosis can threaten limb and life. Most young children who present acutely with pain, limping, and/or loss of function have transient synovitis, which will resolve spontaneously within a few days. A minority will have a bone or joint infection. Clinicians are faced with a diagnostic challenge: children with transient synovitis can safely be sent home, but children with bone and joint infection require urgent treatment to avoid complications. Clinicians often respond to this challenge by using a series of rudimentary decision support tools, based on clinical, haematological, and biochemical parameters, to differentiate childhood osteoarticular infection from other diagnoses. However, these tools were developed without methodological expertise in diagnostic accuracy and do not consider the importance of imaging (ultrasound scan and MRI). There is wide variation in clinical practice with regard to the indications, choice, sequence, and timing of imaging. This variation is most likely due to the lack of evidence concerning the role of imaging in acute bone and joint infection in children. We describe the first steps of a large UK multicentre study, funded by the National Institute for Health Research, which seeks to integrate definitively the role of imaging into a decision support tool, developed with the assistance of individuals with expertise in the development of clinical prediction tools. Cite this article: Bone Joint J 2023;105-B(3):227–229

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244

Aim

Corynebacterium is a rare etiologic agent of BJI. We aimed to describe this rare clinical condition and to assess treatment failure determinants.

Aims. This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment. Methods. A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not. Results. A total of 147 patients were included in the no-mNGS group and 88 in the mNGS group. The mNGS group had a higher detection rate of rare pathogens than the no-mNGS group (21.6% vs 10.2%, p = 0.016). However, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and higher infection control rates compared with the no-mNGS group (p = 0.017, p = 0.003, and p = 0.028, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.957). In culture-negative cases, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and a higher infection control rate than the no-mNGS group (p = 0.036, p = 0.033, p = 0.022, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.748). Conclusion. mNGS improves detection of rare pathogens in BJIs. mNGS testing reduces antibiotic-related complications, shortens hospital stay and antibiotic use duration, and improves treatment success rate, benefits which are particularly evident in culture-negative cases. Cite this article: Bone Joint Res 2024;13(8):401–410

Aim. People awaiting surgery for bone and joint infection may be recommended to stop smoking to improve anaesthetic and surgical outcomes. However, restricting curative surgical treatment to non-smokers on the basis of potentially worse surgical outcomes is not validated for functional outcomes or quality of life differences between patients who do and do not smoke. This study used secondary analysis of trial data to ask: do peri-operative non-smokers have a greater improvement in their quality of life 12 months after surgery for bone and joint infection, compared with non-smokers?. Method. Participants in the SOLARIO and OVIVA clinical trials who had complete baseline and 12 month EQ-5D-5L or EQ-5D-3L scores were included. Smoking status was ascertained at baseline study enrolment from participant self-report. Normalised quality of life scores were calculated for participants at baseline and 12 months, based on contemporaneous health state scores for England. Baseline and 12 month scores were compared to calculate a post-operative increment in quality of life. Results. Mean quality of life increment over 12 months was +0.17 for people who reported smoking peri-operatively (95% confidence interval −0.55 to +0.89), compared to +0.23 for people who did not report smoking peri-operatively (95% confidence interval −0.48 to +0.94). Linear regression analysis found no significant difference between the improvement in quality of life for smokers and non-smokers (p>0.1). Mean increments for both groups were greater than estimates of Minimal Clinically Important Difference in quality of life in musculoskeletal conditions. [1,2]. Conclusions. People who smoke peri-operatively still experience an improvement in quality of life after surgery for orthopaedic infections, commensurate with the improvement experienced by non-smokers. Surgery should not be denied to people on the basis of reported smoking status alone

Aims. It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs. Methods. The AO Trauma Infection Registry is a prospective multinational registry. In total, 229 adult patients with long-bone BJI were enrolled between 1 November 2012 and 31 August 2017 in 18 centres from ten countries. Clinical outcome data, demographic data, and details on infections and treatments were collected. Patient-reported outcomes using the 36-Item Short-Form Health Survey questionnaire (SF-36), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at one, six, and 12 months. The SF-36 mental component subscales were analyzed and correlated with infection characteristics and clinical outcome. Results. The SF-36 physical component summary mean at baseline was 30.9 (95% CI 29.7 to 32.0). At one month, it was unchanged (30.5; 95% CI 29.5 to 31.5; p = 0.447); it had improved statistically significantly at six months (35.5; 95% CI 34.2 to 36.7; p < 0.001) and at 12 months (37.9; 95% CI 36.4 to 39.3; p < 0.001). The SF-36 mental component summary mean at baseline was 42.5 (95% CI 40.8 to 44.2). At one month, it was unchanged (43.1; 95% CI 41.4 to 44.8; p = 0.458); it had improved statistically significantly at six months (47.1; 95% CI 45.4 to 48.7; p < 0.001) and at 12 months (46.7; 95% CI 45.0 to 48.5; p < 0.001). All mental subscales had improved by the end of the study, but mental health status remained compromised in comparison with the average USA population. Conclusion. BJIs considerably impact HRQoL, particularly mental health. Patients suffering from BJIs reported considerable limitations in their daily and social activities due to psychological problems. Impaired mental health may be explained by the chronic nature of BJIs, and therefore the mental wellbeing of these patients should be monitored closely. Cite this article: Bone Jt Open 2024;5(9):721–728

Aim. To investigate the impact of waiting for surgical treatment for bone and joint infection (BJI) on patient self-reported quality of life (QoL). Method. Patients presenting to clinic between January 2019 and February 2020 completed the EuroQol EQ-5D-5L questionnaire. Patients were divided into three groups: surgery performed; on the waiting list for surgery; or decision for non-operative management. All patients were followed-up for 2 years. The EQ-index score was calculated and change from presentation to 1-year and 2-year follow-up was compared across the 3 groups. Mortality at final follow-up was measured in all groups. Results. 188 patients were included. Of these, 98 had an operation performed, 50 were on the waiting list for surgery but did not receive an operation and 40 were treated non-operatively. At presentation, all three groups had similar EQ-5D-5L index scores (surgery:0.412 SD0.351; waiting list:0.510 SD0.320; non-operative management: 0.467 SD0.354; p=0.269). There was a significant improvement in QoL in patients who underwent surgery when compared to their pre-operative state (mean increase of EQ-index score +0.241 in the first year (SD0.333, p<0.001) and +0.259 (SD0.294, p<0.001) in the second year. Patients on the waiting list for surgery had a small time-dependent decrease in EQ-index score at 1 year (−0.077, SD0.282, p=0.188) and 2 years (−0.140, SD0.359, p=0.401). Patients treated non-operatively had similar changes in EQ-index scores at 1 year (−0.052, SD0.309, p=0.561) and 2 years (−0.146, SD 0.234, p=0.221). Patients who had surgery had significantly better QoL at 2-years after treatment compared to other groups (mean EQ-index scores: surgery performed 0.671 vs. waiting list 0.431, p<0.001; surgery performed vs. non-operative management 0.348, p<0.001). Mortality in the operated group was 3.1%, which was similar to patients who were on the waiting list for surgery (6.5%, p=0.394) but lower than patients who were non-operatively managed (14.7%, p=0.014). Conclusions. The Covid-19 pandemic created long waiting times for some patients. Selecting patients with BJI who can safely wait for surgery is difficult. QoL for patients with BJI deteriorates over time if surgery is delayed or not performed. When patients decline surgery, they should be counselled that their QoL is likely to be impaired over time. The relationship between waiting time and mortality merits further study

Aim. To assess whether recurrence of PJI and osteomyelitis impacts patient-reported quality of life (QoL). Method. We studied patients receiving surgical treatment for confirmed PJI or osteomyelitis in one of 26 centres in the UK. Patients completed the EQ-5D-3L questionnaire, directly after surgery, at day 14, day 42, day 120 and day 365 after surgery and were assessed for evidence of recurrence. Results. Of 621 patients with PJI, 99 had recurrent infection (15.9%). Patients with recurrence reported significantly lower QoL at one year after surgery compared to those without recurrence (EQ-5D-3L index score with recurrence: 0.368, SD0.344 vs. no recurrence: 0.592, SD0.315, p<0.001). Patients were grouped based on the timing of their recurrence: <42 days (n=27); 42–120 (n=28); or >120 days (n=44) post-surgery. At the time-point immediately preceding the diagnosis of recurrence, QoL was significantly lower than in corresponding patients without recurrence (recurrence <42 days, p<0.05; 42–120 days, p<0.001; >120 days, p<0.05). In 358 cases of osteomyelitis, 39 patients had recurrent infection (10.9%). Recurrence of osteomyelitis produced significantly lower QoL at one year after surgery compared to patients without recurrent infection (EQ-5D-3L for recurrence: 0.385, SD0.345 vs. no recurrence: 0.634, SD0.349, p<0.001). Patients with recurrence after 120 days (n=21) reported significantly lower QoL than those with no recurrence at the time-point immediately preceding the diagnosis of recurrence (p<0.01). In contrast to patients with PJI, patients with osteomyelitis who had recurrence diagnosed before 120 days (n=18) reported similar outcome scores to patients who did not have recurrence. Conclusion. Failure to eradicate infection greatly affects patient QoL. This study supports the monitoring of EQ-5D-3L among patients treated for bone and joint infections; patients with poorer QoL at follow up should prompt a low threshold for investigation to assess whether recurrence or continued infection is the underlying cause

Aims. The French registry for complex bone and joint infections (C-BJIs) was created in 2012 in order to facilitate a homogeneous management of patients presented for multidisciplinary advice in referral centres for C-BJI, to monitor their activity and to produce epidemiological data. We aimed here to present the genesis and characteristics of this national registry and provide the analysis of its data quality. Methods. A centralized online secured database gathering the electronic case report forms (eCRFs) was filled for every patient presented in multidisciplinary meetings (MM) among the 24 French referral centres. Metrics of this registry were described between 2012 and 2016. Data quality was assessed by comparing essential items from the registry with a controlled dataset extracted from medical charts of a random sample of patients from each centre. Internal completeness and consistency were calculated. Results. Between 2012 and 2016, 30,607 presentations in MM were recorded corresponding to 17,748 individual patients (mean age 62.1 years (SD 18.4); 10,961 (61.8%) males). BJI was considered as complex for 63% of cases (n = 19,355), and 13,376 (44%) had prosthetic joint infections (PJIs). The controlled dataset, available for 19 centres, included 283 patients. Global consistency and completeness were estimated at 88.2% and 88.9%, respectively, considering missing items in the eCRFs as negative results. Conclusion. This national registry is one of the largest prospective databases on BJI and its acceptable data quality parameters allow further use for epidemiological purposes. Cite this article: Bone Joint Res 2020;9(9):635–644

To propose a national specification for hospitals which offer treatment of complex bone and joint infections to adults. Patients with bone and joint infections are treated in a wide variety of hospitals in the UK. A few have developed services with infection physicians, microbiology laboratory support and dedicated orthopaedic and plastic surgeons working together to deliver a multidisciplinary care pathway. However, many patients are treated in non-specialist units leading to multiple, often unsuccessful procedures with long hospital stays, high costs and additional pain and disability. Inappropriate antibiotic therapy without adequate surgery risks antibiotic resistance. A draft specification was written defining the types of patients who should be referred to a specialist unit for treatment. A description of the components which must be available to treat these cases (staffing, expertise, diagnostic support, outcome assessment and governance structure) was proposed. This draft was circulated to infection units in the UK for consideration and agreed with the Health Department in England. Complex bone and joint infections would be best served nationally by 3–6 networks, each with a single specialist centre. This is similar to national arrangements for bone sarcoma treatment. Patients to be referred will include those with:. Chronic osteomyelitis (long bone, pelvis, spine). Chronic destructive septic arthritis. Complex prosthetic joint infections (multiple co-morbidities, difficult/multi-resistant organisms, multiply operated or failed revision surgery). Infected fractures and non-unions. Specialist units should have:. Orthopaedic surgeons who specialise in infection (joint revision, Ilizarov techniques, etc). Infection physicians who can treat medically unwell patients with complex co-mordidities and multi-resistant infections. Plastic surgeons with experience in difficult microsurgical reconstruction techniques. Scheduled (at least weekly) meetings of all of the above, with a radiologist to discuss new referrals and complex cases. A home IV therapy service. Dedicated in-patient beds staffed by infection trained staff. Multi-disciplinary (one-stop) out-patient clinics. Quality measures assessed, including PROMS, clinical success rates, and functional outcome. Education and research programmes. This service specification is a tool for developing regional units. It facilitates the creation of designated centres in a national network (hub and spoke model). This service specification has been agreed and published by NHS England

Aim. bone and joint infection (BJI) in aging population, continues to be associated with significant morbi-mortality. In western Europeans countries, the Gram positive BJI are preponderant. Vancomycin was the “gold standard” and the full treatment requires prolonged antibiotic therapy. Dalbavancin is a semi-synthetic lipoglycopeptideanalog of teicoplanin class of antibiotics with bactericidal activity and a long half-life. The use of dalbavancin in BJI could be an option. Methods. during November 2017 and April 2019, Dalbavancin was used in monotherapy as salvage option in BJI: 1500 mg, 1. st. (D1) and 8. th. day (D8), repeated if needed. The clinical and biological follow up was for 6 months if osteomyelitis or BJI without prosthesis and 1 year if prosthesis (PJI). Results. the demographics of 16 patients are: 75.0% men (n=12), mean age 77.8 years [64–90], 37.5% (n=6) diabetes, 68.8% (n=11) renal failure, 37.5% (n=6) atrial fibrillation, 18.8% (n=3) cardiac bioprosthesis, 31.2% (n=5) lower limb arteriopathy, and one patient with active neoplasia. The BJI characteristic's: 50% (n=8) secondary to health care;5 vertebral osteomyelitis; 12 lower limb BJI : 8 joint infection of witch 6 PJI (4 knee, 2 hip) and 4 foot osteomyelitis; 2 shoulder PJI; 3 patients had 2 or more localisations of BJI. In 68.8% (11/16) BJI, bacteraemia occurred with 68.8% (n=11) of possible or certain infective endocarditis (Duke criteria) and 37.5% (n=6) of deep abscess. The DAIR was of 83.4% (5/6). Monobacterian biopsy in 75.0% (n=12). Out of 32 micro-organisms, 25 were Dalbavancin susceptible:56.0% (14/25) Staphylococcus aureus (10 methicillin susceptible), 3 Streptococcus, 5 Enterococcus faecalis, 2 Corynebacterium, 1 coagulase negative staphylococcus. Mean of 1. st. antibiotherapy: 18.3 days [0–49], with 2 patients who had dalbavancine as only antibiotic. Number of dalbavancine doses: 75% (n=12) patients had 2 injection (D1, D8), 18.8% (n=3), 4 injections D1, D8, D28 and D35 and 1 patient had one dose. Principal reason of changing by dalbavancine: 50% (8/16) poor tolerance of antibiotics, 12.5% (2/16) poor compliance of patient, 18.8% (3/16) poor efficacy of 1. st. antibiotherapy, 18.8 %(3/16) only for the patient's comfort. Clinically success: 75% (12/16) with 5 patients in follow up today. Three patients died and one is cured with teicoplanin and rifampicin. Three patients presented side effects: one diarrhea, one headache and one transient asthenia. No renal damage was found and no allergy. Conclusion. This report highlights the potential role of dalbavancin in treating unstable and weak patients who require long-term antimicrobial therapy with fewer antibiotic choices

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. Current standard of care in the management of bone and joint infection commonly includes a 4–6 week course of intravenous (IV) antibiotics but there is little evidence to suggest that oral antibiotic therapy results in worse outcomes. The primary objective was to determine whether oral antibiotics are non-inferior to IV antibiotics in this setting. Method. This was a parallel group, randomised (1:1), open label, non-inferiority trial across twenty-six NHS hospitals in the United Kingdom. Eligible patients were adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least six weeks of antibiotics and who had received ≤7 days of IV therapy from the date of definitive surgery (or the start of planned curative treatment in patients managed non-operatively). Participants were randomised to receive either oral or IV antibiotics for the first 6 weeks of therapy. Follow-on oral therapy was permitted in either arm. The primary outcome was the proportion of participants experiencing definitive treatment failure within one year of randomisation. The non-inferiority margin was set at 7.5%. Results. Of 1054 participants randomised (527 to each arm) endpoint data were available for 1015 (96.30%). Definitive treatment failure was identified in 141/1015 (13.89%) participants, 74/506 (14.62%) of those randomised to IV therapy and 67/509 (13.16%) of those randomised to oral therapy. In the intention to treat analysis, the imputed risk difference (PO-IV) for definitive treatment failure was −1.38% (90% CI: −4.94, 2.19), thus meeting the non-inferiority criterion (i.e. the upper limit of 95%CI being <7.5%). A complete cases analysis, a per-protocol analysis and sensitivity analyses for missing data confirmed this result. With the exception of intravenous catheter complications, there was no significant difference between the two arms in the incidence of serious adverse events (SAEs). Health economic analysis suggests that the non-surgical treatment costs over one year for patients randomised to oral therapy were approximately £2,700 less than those of IV therapy. Conclusions. Oral antibiotic therapy is non-inferior to IV therapy when used during the first six weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within one year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Funding. The OVIVA study was funded by the National Institute for Health Research Health Technology Assessment programme (Project number 11/36/29)

Aim. Tedizolid is an oxazolidinone antibiotic that: (i) is recommended at the dose of 200 once daily in patients with skin and soft tissue infection; (ii) seems to have a better long-term hematological and neurological safety profile in comparison with linezolid; (iii) remains active on multidrug-resistant (MDR) Gram-positive pathogens. Consequently, it might represent an option as suppressive antimicrobial treatment (SAT) in patients with complex implant-associated bone and joint infection (BJI) due to MDR Gram-positive pathogens. Method. We performed a cohort study (2017–2020) to evaluate the long-term safety of tedizolid (200mg qd) as SAT in patients with implant-associated BJI. In all cases, the use of tedizolid was validated as the last oral treatment option during multidisciplinar meetings in a reference center for the management of BJI. Serious adverse events, any reason for discontinuation, and standard biological data, were prospectively collected. Results. Seventeen patients (13 males; median age 73 years) received tedizolid as SAT for late complex prosthetic-joint infections (n=16) or osteosynthesis (n=1). Pathogens were MDR coagulase negative staphylococci (16 patients), Corynebacterium striatrum (2 patients), Enterococcus faecium (1 patient) and/or S. aureus (1 patient). Tedizolid was always started after a primary treatment (median duration of intravenous 47 days; followed by linezolid in 12 patients including 9 who experienced linezolid-induced serious adverse event) that followed a surgery, mainly debridement and implant retention (13 patients). Median duration of tedizolid was 6 months (min, 1 month; max, 31 months). The only reason for discontinuation was a failure of the conservative strategy that occurred in four patients (17%) during the follow-up. No patients developed a serious adverse event, or a discontinuation of tedizolid due to an adverse event. Anemia was observed in two patients, who had already other known cause of anemia (chronic leukemia and oesophageal varices); stable thrombopenia was observed in a cirrhotic patient (80 G/L, stable during the treatment course of 12 months); and a transient mild neutropenia (1.4 G/L) was observed in another patient (Figure). No neurological adverse event was observed. Conclusions. Tedizolid seems to be a safe option as SAT in patients with complex implantassociated BJI due MDR Gram-positive pathogens. For any tables or figures, please contact the authors directly

Aim. Bone and joint infections (BJI) need frequently prolonged antibiotic treatment at high dosage for a total of 6 or 12 weeks depending the type of infection. Impact of such prolonged antibiotic exposure on the gut microbiota has never been assessed. Method. We performed a national multicentric prospective study of patients with BJI to monitor the gut microbiota dynamic all along antimicrobial treatment. Clinical data and stool collection were performed at the baseline visit (B) within 24h before starting antibiotics, at the end of the treatment (EOT) and 2 weeks after antibiotic withdrawal during a follow-up visit (FU). Microbiota composition was determined by shotgun metagenomic sequencing. Biological markers of gut permeability and inflammation were monitored at each time point. Results. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI and 21 prosthetic joint infections (PJI). At EOT there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI but not in patients with osteosynthesis-related BJI (p<0.05, Wilcoxon test). At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. Principal Component Analysis (PCoA) of the Bray Curtis distance, showed a significant change of the gut microbiota at the end of treatment compared to baseline (p<0.01, PERMANOVA) that only partially recover at FU. The taxonomic analysis showed that microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks to patients treated for 12 weeks. No particular antibiotic (especially fluoroquinolones) was associated with a lower Shannon index or distinct dynamic of recovery at the end of treatment. PCoA analysis of the Bray Curtis distance shows that patients with elevated plasma level of CRP (≥5mg/L) at EOT had a distinct gut microbial composition compared to others. Conclusions. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery 2 weeks after antibiotic withdrawal, independently on the duration of the therapy and on the type of the antibiotic used. Elevated CRP at EOT might reflect persistent alteration of the gut microbiota. Assessment of long-term impact after the end of treatment is on-going

Background. Antibiotic-loaded cement has been used over decades as a local antibiotic delivery for the treatment of bone and joint infections. However, there were some disadvantages such as unpredictable elution, insufficient local concentration and reduced mechanical strength. We developed hydrophilized bone cement and investigated whether it can improve consistent antibiotic release for extended periods to be effective in eradicating joint infection without any changes of mechanical strength. Methods. The experiments consists of preparation of the hydrophilized, vancomycin-loaded bone cement, In vitro test including drug release behavior, mechanical properties by compression test, cytotoxicity, antibacterial effect and animal study. In animal study, Antibiotic cement rod was implanted in the femur of rat osteomyelitis model. Sign of infections were assessed by gross observation, Micro CT and blood analysis at indicated period. Results. The hydrophilized Vancomycin-loaded bone cements showed that continuous release of Vancomycin even over 6 weeks in the drug release test, sufficient mechanical strengths in the compression test and also better anti-bacterial effect compared to other commercially available bone cement. The animal study demonstrated that it has superior inhibition of bacterial proliferation according to imaging and blood analysis compared to control group. Conclusion:. As a results from both in vitro test and animal study, hydrophilized antibiotic bone cement may provide favorable environment to control bone and joint infection by continuous antibiotic release for extended period

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