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

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

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

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

Aim

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

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

Between 1980 and 1984 nine adult patients in the renal unit of Guy's Hospital developed bone and joint infection. The commonest site of infection was the spine. In this series two patients died, a mortality of 22%. The purpose of this paper is to illustrate the pitfalls in the diagnosis and management of bone and joint infection in patients with renal failure and renal transplants

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

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

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

Background/objective: Although several prospective trials have shown the efficacy of sequential intravenous followed by oral antimicrobial regimen in treatment of bone and joint infections, considerable uncertainty exists about ideal antibiotic regimen and optimal duration of antibiotic therapy. The aim of this study was to demonstrate that short course antibiotic therapy combined with surgical drainage and followed by oral antibiotic therapy is quite adequate and suggested a scoring system as a comfortable and reliable tool to adjust the route of drug administration. Methods: Thirty-three cases of acute hematogenous bone or joint infection were randomly treated with short term (7 days for joint infection, l0 days for bone infection) or a long-term (14 days and 21 days, respectively) intravenous antibiotics after surgical drainage. The treatment outcome was measured through a detailed scoring system that included the ability to eradicate infection, the functional status of the limb, and the radiological appearance of the bone and joint. Criteria for discontinuation of parenteral antibiotic Scoring criteriapoints. Clinical evaluation. A: improved active motion of the joint: l. B: Painless active motion of the joint: 2. C: improvement in A & B:3. Radiological findings. A: progressive osteolysis ormultifocal involvement: 0. B: absence of the above findings*: 1. Laboratory evaluation. A: drop of 50.00/mm3 in WBC count or return to normal range (5.000–10.000 /mni3): 0.5. B: drop in ESR of 30 mm/hr or return to level of 30 mm/hr or less: 0.5. Total score: 5. *Pure periosteal elevation received a score of 1. Patients with a score > or equal to 4 would be switched to oral antibiotic. Results: The average follow up was 19 months. The scoring system had the following results: Infection was eradicated in both groups. Radiological scoring for septic arthritis was full for both groups and had a non-significant difference P> 0.05 between the 2 groups for osteomyelitis. The mean functional scoring between the short-term group and long-term group were similar P> 0.05. Overall, excellent or good results were achieved in both groups. No fair or poor results were observed. The average hospital cost for a patient in long-term group was twice that of a patient in short-term group. Conclusion: It is concluded that for bone or joint infection in children who have received appropriate and early surgical treatment, intravenous antibiotics given for 7 days in joint infections and 10 days in bone infections, followed by 4 weeks of oral antibiotics, is an adequate treatment. A decision on prolonging the duration of parenteral antibiotics should be based on a combination of clear clinical, laboratory, and radiographic criteria, such us the scoring system presented in this article

Introduction. Microbiological diagnosis of bone and joint infections (BJIs) currently relies on standard cultures which are time consuming and lack sensitivity. Various molecular approaches have been described and allowed improvement of BJI diagnosis. This study evaluated for the first time the performance of a DNA microarray-based assay (Prove-it™ Sepsis assay, PISA) for the rapid (<6 hours) detection and identification of 50 different species involved in BJI directly from clinical samples. Material and methods. We retrospectively selected 130 bone and joint samples (67 synovial fluids and 63 bone biopsies) including 114 positive and 16 negative samples. The microbiological diagnosis had been previously established either by culture(C+, n=53) or by PCR16S and sequencing when culture was negative (C-/PCR+). The positive samples were selected to match the species targeted on the DNA microarray. DNA extraction was performed before proceeding to PISA amplification and hybridization on every selected sample. Results. Among the 16 negative samples, one was detected positive with S. epidermidis by PISA, result that was secondarily confirmed using specific PCR. Among the 114 positive samples, 62.3% were positive using PISA with highly concordant identification compared to culture and PCR16S/sequencing results. Forty-three samples (37.7%) remained negative, illustrating a defect of sensitivity. However, PISA accurately detected methicillin resistance not only among the 16 C+/PISA+ Staphylococcus species (n=5) but also among the 28 C-/PCR16S+ Staphylococcus species (n=12) offering crucial rapid information to adapt the treatment of staphylococcal BJIs. Seven polymicrobial samples were also identified without extensive experiments. Discussion – Conclusion. Even if the sensitivity deserves to be improved by optimizing DNA extraction and investigating on human DNA interference, these preliminary promising results highlight that this new and simple microarray method could be in the future an alternative to conventional PCR16S for the diagnosis of BJI

Aim. To demonstrate the use of indium-111 white-cell labelled SPECT CT (In111-WC-SPECT-CT) in bone infection. Method. This novel imaging modality is useful in bone infection. We present three cases of complex osteomyelitis to illustrate this. All were imaged with conventional modalities, but conclusive diagnosis could not be achieved. In111-WC-SPECT-CT was used to provide the definitive imaging that allowed successful treatment. Results. Case 1- A 29 y/o Male with spina bifida presented with chronic calcaneal osteomyelitis. Previous treatment included debridement, but recurrent infection ensued. MRI showed widespread changes consistent with infection throughout the calcaneus and a below knee amputation was planned. In111-WC-SPECT-CT (Figure 1) showed a distinct localised nidus of infection. A targeted sequestrectomy was performed and the patient has been infection free for four years. He was spared the amputation. Case-2- A 73 y/o male presented with a radiation induced colo-cutaneous fistula and pelvic chronic osteomyelitis. Surgical treatment included multiple debridements and sequestrectomy. He re-presented pain with pain in his pelvis six months later. MRI was performed and oedema seen in the bone. This was presumed to be infection and further surgery was planned. An In111-WC-SPECT-CT was then performed and confirmed no residual bone infection. The patient was spared surgery. Case-3- A 38 y/o female was involved in an RTA 6 months prior to presentation. She underwent fixation of her tibia with skin grafting for an open fracture. There was clinical suspicion of deep infection. The metalwork made MRI difficult to interpret. An In111-WCC-SPECT-CT confirmed infection around the metal screw and this evidence instigated a prolonged course of antibiotics to suppress the infection. The screw will be removed after the fracture heals. Conclusions. In-111-WC-SPECT-CT is an emerging imaging modality. We present three cases of complex bone and joint infection; where this imaging has altered the course of treatment

Bone and joint infections are not only common but their management can be technically complex. They carry significant healthcare costs and are a daunting experience for patients [1]. Frequently, multiple operations are required in order to treat the infection. Each surgical intervention usually results in greater bone loss, worsening skin and soft tissue scarring and increasingly diverse and resistant micro- organisms [2]. Specialist bone infection units involving highly integrated orthopaedic and plastic surgery, as well as infection physicians, may improve patient outcomes [3–4]. However, it is difficult to determine the hierarchy of factors contributing to outcome of treatment. This problem is confounded by a lack of structured, prospective data collection in many units around the world. In 2014, we designed a modular database which allows collection of patients’ details, components of the disease, the treatment, microbiology, histology, clinical outcome and patient-reported outcome measures (PROMS). The registry was implemented in November 2014 and has already demonstrated its function as a Hospital-wide service evaluation tool. Over 200 patients have been referred to the unit and their baseline demographic information registered. Their progress through the bone infection unit patient pathway is prospectively monitored with use of the registry and data collection ongoing. We aim to present the preliminary clinical outcomes of these 200 patients including surgical procedures performed, key microbiology results, antibiotic treatment regimens and patient reported outcomes. Our goal is to demonstrate that a bone infection registry is an integral part of infection management clinical practice. It can be used for designing service provision, assist in allocating healthcare resources and expand the evidence base for specialist bone infection units in managing complex orthopaedic infections

Aim

Antibiotic-eluting calcium compounds can be used to deliver antibiotics in the management of prosthetic joint infection (PJI). Described omplications include wound drainage, heterotopic ossification(HO) as well as hypercalcaemia which is potentially life threatening.

The aim of this study is to assess the incidence of hypercalcaemia and other complications between two calcium based antibiotic delivery systems.

Aim

Accurate diagnosis is key in correctly managing prosthetic joint infection (PJI). Our aim is to compare the preoperative performance of three PJI definitions comparing it to definitive postoperative classification.

Aim

Leading etiology of Bone and Join infections (BJI), Staphylococcus aureus (SA) is responsible for difficult-to-treat infections mainly because of three persistence factors: (i) biofilm formation, (ii) persistence within bone cells and (iii) switch to the small colony variant (SCV) phenotype. The impact of rifampin on these mechanisms gave it a prominent place in orthopedic device-associated BJI. However, resistance emergence, intolerance and drug interactions cause significant concerns. In this context, other rifamycins – namely rifapentine and rifabutin – have poorly been evaluated, particularly toward their ability to eradicate biofilm-embedded and intracellular reservoirs of SA.

Background. With promising antibiofilm properties, rifampicin is considered as a cornerstone in the complementary treatment of bone and joint infections. But, achieving an adequate concentration of rifampicin long-term in bone tissue is a challenge. Long-term systemic administration also comes with concomitant side effects. Thus, local delivery of rifampicin in a carrier to ensure the high local concentration of antibiotic in surgical site after intervention due to infection could be a valuable alternative. However, an ideal platform for local delivery of rifampicin is still lacking. A calcium sulphate/hydroxyapatite (CaS/HA) (Cerament, Bonesupport AB, Sweden) biomaterial was used as a local delivery platform. Here we aimed 1) to evaluate the injectability of CaS/HA hand-mixed with rifampicin at various concentrations up to maximum one daily dose used systemically in clinical practice 2) to test a clinically used and commercially available mixing device containing the biphasic ceramic with rifampicin. Materials & Methods. Three different concentrations (100 mg, 300 mg and 600 mg) of rifampicin powder (Rifampicin Ebb, Sanofi S.P.A, Italy) diluted in 5 mL of mixing solution (C-TRU, Bonesupport AB, Sweden) were used. Rifampicin solution was mixed to the CaS/HA powder and the injectability of the CaS/HA plus rifampicin composite was evaluated by extruding 250 µL of paste manually through a graduated 1 mL syringe connected to an 18G needle (Ø=1.2 mm, L=4 cm). Mixing was done with a spatula for 30 s at 22°C ±1°C. Total weight of the paste before and after extrusion were measured. To normalize the amount of composite that remained in the needle and syringe tip after injection, the mean of the paste extruded from the syringe at 3 min was calculated for the tested concentrations (normalized value). Injectability (%) was calculated by dividing the weight of the paste extruded from the syringe with normalized value. Each test was repeated for three times at various time points (3, 5, 7 and 9 min). Additionally, 300 mg rifampicin was chosen to mix with the CaS/HA in a commercially available mixing system, which is used clinically. Results. All three combinations of CaS/HA plus rifampicin (100 mg, 300 mg & 600 mg) could be completely extruded from 1 mL syringes at 3 min. At 5 min, 100 mg & 300 mg could still be injected, whereas 600 mg was uninjectable or solidified. At 7 min, rifampicin 100 mg & 300 mg showed 34% and 11% of injectability respectively. At 9 min, no injectability was observed. The material was completely set within 15 minutes with all concentrations. With commercial mixing system, at the recommended injection time of 4 min, 78% of the CaS/HA plus rifampicin (300 mg) composite could be injected. Conclusions. The injectability was reduced with the increasing concentration of rifampicin. CaS/HA plus rifampicin (100 mg and/or 300 mg) could be used by hand mixing and transferred to a syringe or by using an available mixing system containing the ceramic. For higher concentrations of rifampicin, the rheological properties of the ceramics have to be modified for injectability

Aims. Calcium sulphate (CaSO. 4. ) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO. 4. as an adjunct to the routine therapy of bone and joint infections. Patients and Methods. A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. Results. The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. . Conclusion. This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO. 4. as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537–44

Paediatric bone and joint infections remain common in low- and middle-income countries (LMICs). We aimed to determine the complication rate and incidence of disseminated infection in paediatric bone and joint infections in an LMIC setting. Secondly, we aimed to elucidate factors associated with complications and disseminated disease. We retrospectively reviewed our database for children that presented with bone and joint infections between September 2015 and March 2019. Data were extracted to identify factors that were associated with development of complications and disseminated infection. We analysed 49 children. The median age at presentation was 6 years (range 1 month to 12 years). Locally advanced disease was present in 13 children (27%). The remaining 36 children were evenly divided (18/49 each, 37%) between isolated AHOM and SA, respectively. Disseminated disease was present in 16 children (33%) and was associated with locally advanced disease, an increase in number of surgeries and an increased length of stay. Twenty-six complications were documented in 22 (45%) children. Chronic osteomyelitis developed in 15/49 (31%) cases, growth arrest in 5/49 (10%), and pathological fracture, DVT and septic shock in 2/49 (4%) each. Complicated disease was associated with locally advanced disease, a higher number of surgeries, disseminated disease and an increased length of stay. Sixty five percent of cases cultured Staphylococcus aureus, while 25% (12/49) were culture negative. The median time from admission to surgery was one day, and the median time from onset of symptoms to surgery was seven days. We found a high complication rate. One third of patients had locally advanced disease, and this was associated with the development of complications and disseminated disease. Further studies are needed to be able to predict which children will have poor outcomes

Aim. To evaluate whether sonication of implant material and subsequent culturing add clinical relevance to culturing of tissue biopsies for improved antibiotic treatment in treatment of bone and joint infection. Method. A retrospective examination of patients’ charts and microbiological analyses in patients who had explanted material (plates, screws, k-wires and prostheses) send for sonication between December 2020 and April 2022. Results. 77/143 (54 %) patients had complete agreement between the cultures from tissue biopsies and sonication fluid. 66/143 (46 %) patients had partial or no agreement between the cultures from tissue biopsies and sonication fluid. Of the 66 patients, 31 (47 %) had a culture positive sonication fluid and tissue biopsies that were positive with one or more bacterial isolates. 26/66 (39 %) patients had a culture positive sonication fluid and tissue biopsies that were negative. 9/66 (14 %) patients had negative sonication fluid and positive tissue biopsies. Of the 26 patients with culture positive sonication fluid and culture negative tissue biopsies, virulent bacteria were found in 5 (19 %) patients, making the diagnosis and treatment of infection straight forward. The remaining 21 (81 %) patients had C. acnes, S. epidermidis and CoNS in the sonication fluid, which made the diagnosis less evident but none the less gave the clinician a relevant treatment option. Conclusion. In this study a high concordance was found between cultures from tissue biopsies and sonication fluid. Additionally, in a small group of patients with culture negative tissue biopsy, the culture of sonication fluid was essential to the identification infections agent. This indicates that culture of sonication fluid is an important diagnostic tool in bone and joint infection, especially in the absence of positive tissue cultures

Aims. This study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI). Methods. In this single-centre, retrospective analysis of prospectively collected data, patients with an indicated revision surgery after a total hip or knee arthroplasty were included between 2015 and 2020. A standardized diagnostic workup was performed, identifying the components of the EBJIS, ICM, and IDSA criteria in each patient. Results. Of 206 included patients, 101 (49%) were diagnosed with PJI with the EBJIS definition. IDSA and ICM diagnosed 99 (48%) and 86 (42%) as infected, respectively. A total of 84 cases (41%) had an infection based on all three criteria. In 15 cases (n = 15/206; 7%), PJI was present when applying only the IDSA and EBJIS criteria. No infection was detected by one definition alone. Inconclusive diagnoses occurred more frequently with the ICM criteria (n = 30/206; 15%) compared to EBJIS (likely infections: n = 16/206; 8%) (p = 0.029). A better preoperative performance of the EBJIS definition was seen compared with the ICM and IDSA definitions (p < 0.001). Conclusion. The novel EBJIS definition identified all PJIs diagnosed by any other criteria. Use of the EBJIS definition significantly reduced the number of uncertain diagnoses, allowing easier clinical decision-making. Cite this article: Bone Joint Res 2022;11(9):608–618

Aim. Local antibiotic treatment for bone and joint infections offers direct delivery of high concentrations of antibiotics with reduced systemic exposure and favourable safety profile. However, the possibility of prolonged release of antibiotics at sub-therapeutic levels creates concern about the possible development of antimicrobial resistance. We investigated patients with recurrent bone and joint infection for evidence of antimicrobial resistance emerging from the use of local antibiotics. Method. 125 patients with recurrent infection (prosthetic joint infection, fracture related infection and osteomyelitis) in the UK between 2007 and 2021 were identified. Electronic patient records (including operative notes, pathology results and prescriptions) were reviewed to extract site of infection, date of surgery, the use of local antibiotics, culture results, empiric and definitive antibiotic therapy. All antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary guidelines (BSAC and EUCAST). Results. Local antibiotics were used in 74/125 (59.2%) of patients. Agents used were Gentamicin 53/125 (42.4%), Tobramycin 18/125 (14.4%), and vancomycin in 19/125 (15.2%). Combined gentamicin and vancomycin usage was seen in 16/125 patients (12.8%). Gentamicin non-sensitivity was common in this cohort with frequent aminoglycoside use. At index procedure, a Gentamicin non-sensitive organism was cultured in 51/125 patients (40.8%). At re-operation this proportion was lower: 40/125 (32%). There was no statistically significant difference in the rate of Gentamicin resistance at reoperation comparing patients who previously received local aminoglycosides with those who had not (21/71, 29.8% vs 19/54, 35.2% p=0.6, chi-squared test). In 48/125 (38.4%) of patients, the same species was isolated during the index and recurrence surgery. We identified 7 cases with new aminoglycoside resistance arising at the second procedure. In 2/7 – S. aureus and E. faecalis - aminoglycoside resistance was the only change in antimicrobial sensitivity. In 5/7, there were at least 2 additional changes in observed antimicrobial sensitivity. 3/74 (4%) of cases who initially received local aminoglycoside cultured organisms with aminoglycoside resistance at recurrence. 4/51 (7.8%) of those who did not receive local or systemic aminoglycoside at index surgery cultured resistant organisms (chi square 0.82; p=0.365). Conclusions. As a group, patients whose treatment for orthopaedic infection included local antibiotics did not exhibit higher rates of specific antimicrobial resistance compared with those not treated with local antibiotics. However we did identify cases where Gram positive bacteria developed aminoglycoside resistance regardless of their initial antimicrobial therapy. This should be considered in antimicrobial choice during surgery for recurrence

Aims. Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI. Methods. The study included 48 THAs in 48 patients with a clinical suspicion of PJI, but who did not meet European Bone and Joint Infection Society (EBJIS) PJI criteria preoperatively, out of 105 patients undergoing revision THA at our institution for possible PJI between November 2020 and December 2022. Intraoperatively, synovial fluid calprotectin was measured with LFI. Cases with calprotectin levels ≥ 50 mg/l were considered infected and treated with two-stage revision THA; in negative cases, one-stage revision was performed. At least five tissue cultures were obtained; the implants removed were sent for sonication. Results. Calprotectin was positive (≥ 50 mg/l) in 27 cases; out of these, 25 had positive tissue cultures and/or sonication. Calprotectin was negative in 21 cases. There was one false negative case, which had positive tissue cultures. Calprotectin showed an area under the curve of 0.917, sensitivity of 96.2%, specificity of 90.9%, positive predictive value of 92.6%, negative predictive value of 95.2%, positive likelihood ratio of 10.6, and negative likelihood ratio of 0.04. Overall, 45/48 patients were correctly diagnosed and treated by our algorithm, which included intraoperative calprotectin measurement. This yielded a 93.8% concordance with postoperatively assessed EBJIS criteria. Conclusion. Calprotectin can be a valuable tool in facilitating the intraoperative decision-making process for cases in which chronic PJI is suspected and diagnosis cannot be established preoperatively. Cite this article: Bone Joint J 2024;106-B(5 Supple B):118–124

Aims. The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI). Methods. In this retrospective diagnostic study, patients undergoing revision surgery after total hip or knee arthroplasty (n = 119) between January 2015 and July 2018 were included. Multiple specimens of the periprosthetic membrane and pseudocapsule were obtained for histopathological analysis at revision arthroplasty. Based on the Infectious Diseases Society of America (IDSA) 2013 criteria, the International Consensus Meeting (ICM) 2018 criteria, and the European Bone and Joint Infection Society (EBJIS) 2021 criteria, PJI was defined. Using a mixed effects logistic regression model, the sensitivity and specificity of the histological diagnosis were calculated. The optimal number of periprosthetic tissue specimens for histopathological analysis was determined by applying the Youden index. Results. Based on the EBJIS criteria (excluding histology), 46 (39%) patients were classified as infected. Four to six specimens showed the highest Youden index (four specimens: 0.631; five: 0.634; six: 0.632). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of five tissue specimens were 76.5% (95% confidence interval (CI) 67.6 to 81.4), 86.8% (95% CI 81.3 to 93.5), 66.0% (95% CI 53.2 to 78.7), and 84.3% (95% CI 79.4 to 89.3), respectively. The area under the curve (AUC) was calculated with 0.81 (as a function of the number of tissue specimens). Applying the ICM and IDSA criteria (excluding histology), 40 (34%) and 32 (27%) patients were categorized as septic. Three to five specimens had the highest Youden index (ICM 3: 0.648; 4: 0.651; 5: 0.649) (IDSA 3: 0.627; 4: 0.629; 5: 0.625). Conclusion. Three to six tissue specimens of the periprosthetic membrane and pseudocapsule should be collected at revision arthroplasty and analyzed by a pathologist experienced and skilled in interpreting periprosthetic tissue. Cite this article: Bone Joint J 2023;105-B(2):158–165

Aims. Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. Methods. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test. Results. AGR, CAR, and CRP were associated with PJI (p < 0.001). Sensitivities were 62.5% (95% CI 54.3 to 70.0), 73.6% (95% CI 65.8 to 80.1), and 71.5% (95% CI 63.6 to 78.3), respectively. Specificities were calculated with 84.7% (95% CI 77.5 to 89.9), 86.3% (95% CI 79.2 to 91.2), and 87.8% (95% CI 80.9 to 92.4), respectively. The AUC of CRP (0.797 (95% CI 0.750 to 0.843)) was significantly higher than the AUC of AGR (0.736 (95% CI 0.686 to 0.786), p < 0.001), and similar to AUC of CAR (0.799 (95% CI 0.753 to 0.846), p = 0.832). Decreased sensitivities were observed in PJIs caused by low-virulence organisms (AGR: 60%, CAR: 78%) compared to high-virulence pathogens (AGR: 80%, p = 0.042; CAR: 88%, p = 0.158). Higher sensitivities were seen in acute haematogenous (AGR: 83%, CAR: 96%) compared to chronic PJIs (AGR: 54%, p = 0.001; CAR: 65%, p < 0.001). Conclusion. Serum AGR and CAR showed limited diagnostic accuracy (especially in low-grade and chronic infections) and did not outperform the established marker CRP in our study. Hence, neither parameter can be recommended as an additional tool for diagnosing PJI. Cite this article: Bone Joint Res 2024;13(8):372–382

Aims. A higher failure rate has been reported in haematogenous periprosthetic joint infection (PJI) compared to non-haematogenous PJI. The reason for this difference is unknown. We investigated the outcome of haematogenous and non-haematogenous PJI to analyze the risk factors for failure in both groups of patients. Methods. Episodes of knee or hip PJI (defined by the European Bone and Joint Infection Society criteria) treated at our institution between January 2015 and October 2020 were included in a retrospective PJI cohort. Episodes with a follow-up of > one year were stratified by route of infection into haematogenous and non-haematogenous PJI. Probability of failure-free survival was estimated using the Kaplan-Meier method, and compared between groups using log-rank test. Univariate and multivariate analysis was applied to assess risk factors for failure. Results. A total of 305 PJI episodes (174 hips, 131 knees) were allocated to the haematogenous (n = 146) or the non-haematogenous group (n = 159). Among monomicrobial infections, Staphylococcus aureus was the dominant pathogen in haematogenous PJI (76/140, 54%) and coagulase-negative staphylococci in non-haematogenous PJI (57/133, 43%). In both groups, multi-stage exchange (n = 55 (38%) in haematogenous and n = 73 (46%) in non-haematogenous PJI) and prosthesis retention (n = 70 (48%) in haematogenous and n = 48 (30%) in non-haematogenous PJI) were the most common surgical strategies. Median duration of antimicrobial treatment was 13.5 weeks (range, 0.5 to 218 weeks) and similar in both groups. After six years of follow-up, the probability of failure-free survival was significantly lower in haematogenous compared to non-haematogenous PJI (55% vs 74%; p = 0.021). Infection-related mortality was significantly higher in haematogenous than non-haematogenous PJI (7% vs 0% episodes; p = 0.001). Pathogenesis of failure was similar in both groups. Retention of the prosthesis was the only independent risk factor for failure in multivariate analysis in both groups. Conclusion. Treatment failure was significantly higher in haematogenous compared to non-haematogenous PJI. Retention of the prosthesis was the only independent risk factor for failure in both groups. Cite this article: Bone Joint J 2023;105-B(12):1294–1302

Aims. This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection. Methods. A total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years’ clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery. Results. The rate of PJI for all identified MoM THAs was 3.5% (41/1,171), with a mean follow-up of 10.9 years (2.0 to 20.4). Of the patients included in the final cohort, 8.2% (27/328) had PJI, with a mean follow-up of 12.2 years (2.3 to 20.4). Among this cohort, 31.1% (102/328) had a history of pseudotumour. The rate of PJI in these patients was 14.7% (15/102), which was greater than those without pseudotumour, 5.3% (12/226) (p = 0.008). Additionally, logistic regression analysis showed an association between history of pseudotumour and PJI (odds ratio 4.36 (95% confidence interval 1.77 to 11.3); p = 0.002). Optimal diagnostic cutoffs for PJI in patients with history of pseudotumour versus those without were 33.1 mm/hr and 24.5 mm/hr for ESR and 7.37 mg/dl and 1.88 mg/dl for CRP, respectively. Conclusion. Patients with history of pseudotumour secondary to MoM THA had a higher likelihood of infection than those without. While suspicion of infection should be high for these patients, ESR and CRP cutoffs published by the European Bone and Joint Infection Society may not be appropriate for patients with a history of pseudotumour, as ESR and CRP levels suggestive of PJI are likely to be higher than for those without a pseudotumour. Additional investigation, such as aspiration, is highly recommended for these patients unless clinical suspicion and laboratory markers are low. Cite this article: Bone Joint J 2024;106-B(6):555–564

Aims. The number of revision arthroplasties being performed in the elderly is expected to rise, including revision for infection. The primary aim of this study was to measure the treatment success rate for octogenarians undergoing revision total hip arthroplasty (THA) for periprosthetic joint infection (PJI) compared to a younger cohort. Secondary outcomes were complications and mortality. Methods. Patients undergoing one- or two-stage revision of a primary THA for PJI between January 2008 and January 2021 were identified. Age, sex, BMI, American Society of Anesthesiologists grade, Charlson Comorbidity Index (CCI), McPherson systemic host grade, and causative organism were collated for all patients. PJI was classified as ‘confirmed’, ‘likely’, or ‘unlikely’ according to the 2021 European Bone and Joint Infection Society criteria. Primary outcomes were complications, reoperation, re-revision, and successful treatment of PJI. A total of 37 patients aged 80 years or older and 120 patients aged under 80 years were identified. The octogenarian group had a significantly lower BMI and significantly higher CCI and McPherson systemic host grades compared to the younger cohort. Results. The majority of patients were planned to undergo two-stage revision, although a significantly higher proportion of the octogenarians did not proceed with the second stage (38.7% (n = 12) vs 14.8% (n = 16); p = 0.003). Although there was some evidence of a lower complication rate in the younger cohort, this did not reach statistical significance (p = 0.065). No significant difference in reoperation (21.6% (n = 8) vs 25.0% (n = 30); p = 0.675) or re-revision rate (8.1% (n = 3) vs 16.7% (n = 20); p = 0.288) was identified between the groups. There was no difference in treatment success between groups (octogenarian 89.2% (n = 33) vs control 82.5% (n = 99); p = 0.444). Conclusion. When compared to a younger cohort, octogenarians did not show a significant difference in complication, re-revision, or treatment success rates. However, given they are less likely to be eligible to proceed with second stage revision, consideration should be given to either single-stage revision or use of an articulated spacer to maximize functional outcomes. Cite this article: Bone Joint J 2024;106-B(8):802–807

Aims. Periprosthetic joint infections (PJIs) and fracture-related infections (FRIs) are associated with a significant risk of adverse events. However, there is a paucity of data on cardiac complications following revision surgery for PJI and FRI and how they impact overall mortality. Therefore, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality in this patient cohort. Methods. We prospectively included consecutive patients at high cardiovascular risk (defined as age ≥ 45 years with pre-existing coronary, peripheral, or cerebrovascular artery disease, or any patient aged ≥ 65 years, plus a postoperative hospital stay of > 24 hours) undergoing septic or aseptic major orthopaedic surgery between July 2014 and October 2016. All patients received a systematic screening to reliably detect PMI, using serial measurements of high-sensitivity cardiac troponin T. All-cause mortality was assessed at one year. Multivariable logistic regression models were applied to compare incidence of PMI and mortality between patients undergoing septic revision surgery for PJI or FRI, and patients receiving aseptic major bone and joint surgery. Results. In total, 911 consecutive patients were included. The overall perioperative myocardial injury (PMI) rate was 15.4% (n = 140). Septic revision surgery for PJI was associated with a significantly higher PMI rate (43.8% (14/32) vs 14.5% (57/393); p = 0.001) and one-year mortality rate (18.6% (6/32) vs 7.4% (29/393); p = 0.038) compared to aseptic revision or primary arthroplasty. The association with PMI persisted in multivariable analysis with an adjusted odds ratio (aOR) of 4.7 (95% confidence interval (CI) 2.1 to 10.7; p < 0.001), but was not statistically significant for one-year mortality (aOR 1.9 (95% CI 0.7 to 5.4; p = 0.240). PMI rate (15.2% (5/33) vs 14.1% (64/453)) and one-year mortality (15.2% (5/33) vs 9.1% (41/453)) after FRI revision surgery were comparable to aseptic long-bone fracture surgery. Conclusion. Patients undergoing revision surgery for PJI were at a risk of PMI and death compared to those undergoing aseptic arthroplasty surgery. Screening for PMI and treatment in specialized multidisciplinary units should be considered in major bone and joint infections. Cite this article: Bone Joint J 2022;104-B(6):696–702

Aim. Multidisciplinary team (MDT) management of complex bone and joint infections (BJI) is increasingly implemented but studies evaluating this approach are scarce. We assessed the effectiveness of our MDT by analyzing the adherence to its treatment decisions. Method. A cohort study was conducted comprising patients with complex BJI of which the management was discussed during MDT meetings between 2015 and 2022 in a tertiary care academic hospital. Patient characteristics and MDT data were obtained from electronic patient records. Results. The analysis included 1321 MDT case decisions on 509 patients. During the study period, the number of patients discussed by the MDT increased from 2.7 to 5.5 per meeting. The percentage of discussed patients with BJI other than prosthetic joint infections (PJI) increased from 26% to 52%. The overall adherence rate to MDT decisions was 92.1%. Reasons for non-adherence were disagreement with the MDT whether cure was achieved or not (34%), new clinical information that was not available during the MDT meeting (12%), preference for suppressive antibiotic treatment over surgery (8%) or not recorded in the patient file (46%). Conclusions. Over the years, the MDT meeting content expanded from mainly PJI to all complex BJI. The high adherence rate to MDT decisions was indicative of an effective MDT. Analysis of adherence is a useful tool to evaluate an MDT and can be used to improve its quality. Different aspects of an MDT need to be evaluated to fully determine its impact and to help improve the care for patients with complex BJI

Aim. Debridement, antibiotics and implant retention (DAIR) are considered as an optimal curative treatment option for prosthetic joint infection (PJI) when the biofilm is still immature and radical debridement is achievable. There are two main groups of patients suitable for DAIR. Those with an early acute PJI and patients with acute hematogenous PJI. However, there is also a third group of early PJI resulting from a wound healing problem or leaking hematoma. These may be either high or low grade depending on the microorganisms that infected the artificial joint “per continuitatem”. Methods. We retrospectively analysed 100 successive DAIR procedures on prosthetic hip and knee joints performed between January 2010 and January 2022, from total of 21000 primary arthroplasties implanted within the same time period. We only included PJI in primary total replacements with no previous surgeries on the affected joint. Patients data (demographics, biochemical, microbiological, histopathological results, and outcomes) were collected from hospital bone and joint infection registry. The aim of surgery was radical debridement and the mobile parts exchange. The standardized antibiotic regime based on antibiofilm antibiotics. Results. The mean age of patients was 70 years (60% women, 43 hips, 57 knees) with a mean follow-up of 3 years. 45 cases were early acute or related to wound healing problems, 55 were hematogenous PJI. 25 patients received preoperative antibiotics. 6 of these were culture negative. The mean symptom duration was 7 days. Mean age of the prosthesis was 30 days for early, and 1064 days for the hematogenous group. Conclusions. In our cohort the success rate of DAIR is 94% which indicates that the protocol is highly successful in PJI with short-lasting symptoms and “debridable” joints. Antibiotic protocol violation and duration of symptoms may have a role in failures

Aim. Pelvic osteomyelitis following pressure ulceration results in substantial patient morbidity. Previous studies have reported a heterogenous approach to diagnosis and medical management by physicians, suggesting equipoise on key clinical questions. This study hypothesised that the same equipoise exists amongst Orthopaedic surgeons. Method. An 18-question multiple-choice questionnaire was designed through an iterative feedback process until the final version was agreed by all authors. Likert-type scale responses were used with graded responses (e.g., never/fewer than half of patients/around half of patients/more than half of patients/every patient). The online survey was sent to members of the Musculoskeletal Infection Society (MSIS), the European Bone and Joint Infection Society (EBJIS), and the ESCMID Study Group for Implant-Associated Infections (ESGIAI). No incentive for participation was provided. Results. Amongst respondents, 22/41 were based in Europe and 10/41 from the USA. The majority (29/41) had been in clinical practice between 5—24 years. There was a high priority placed on bone biopsy histology, culture-positive bone sampling, and palpable bone without periosteal covering for diagnosis. Multidisciplinary team approach with plastic surgery involvement at the index procedure was advocated. The strongest indications for surgical intervention were source control for sepsis, presence of an abscess/collection, and prevention of local osteomyelitis progression. Physiological/psychological optimisation and control of acute infection were the primary determinants of surgical timing. There was low utilisation of adjunctive surgical therapies. Local/regional primary tissue transfer or secondary healing with/without VAC were the preferred techniques for wound closure. Recurrent osteomyelitis was the most common reason for prolonged antimicrobial therapy. The majority received bedside advice from an infectious disease-specialist but a quarter of respondents preferred telephone advice. Conclusions. Amongst an international cohort of Orthopaedic Surgeons there was a heterogenous diagnostic and therapeutic approach to pressure-related pelvic osteomyelitis

Abstract Background. The treatment of bone and joint infections (BJI) involving multi-drug resistant bacteria remains a challenge. MDR Staphylococcus epidermidis (MDRSE) clones, resistant to methicillin, clindamycin, levofloxacin, rifampicin and even linezolid, have been reported worldwide. The interest of delafloxacin (DFX), theoretically active on MRSA, remains to be evaluated with respect to MDRSE. Purpose. Our objective was to evaluate during a retrospective multicenter study the DFX minimal inhibitory concentrations (MICs) and compare its efficacy between ofloxacin-susceptible and ofloxacin-resistant S. epidermidis clinical strains involved in BJI. Methods. In this multicenter retrospective study (Reference centers from the West part of France, CRIOGO), 529 strains were collected mostly from BJI. DFX MICs were determined by using a 0.5 Mc Farland bacterial inoculum on Mueller-Hinton agar plates with gradient strips incubated for 24h at 35°C. For S. aureus, breakpoints differentiate skin and soft tissue infections from other infections. Breakpoints followed 2022 EUCAST criteria, with S. aureus values adopted for S. epidermidis. Results. Of the 529 strains collected, 355 were from prosthetic infections, 159 from synthetic infections and 15 from non-device infections. 152 strains were susceptible to ofloxacin (110 males vs 42 females) and 377 resistant (210 vs 167). As presented in Figure 1, all the ofloxacin-susceptible strains presented a DFX MIC ≤0.006mg/L. Resistant strains presented a double population distribution, with 3.7% categorized susceptible according to skin and soft tissues infections breakpoint, against 88.9% according to other breakpoint infections (0.016 or 0.25mg/L respectively). Conclusion. DFX shows excellent activity against ofloxacine-susceptible strains. Concerning the ofloxacin-resistant strains, more than 80% strains or less than 10% can be considered as DFX-susceptible depending on the breakpoints used. Further clinical studies are needed to validate the real breakpoints that must be used in MDRSE BJI, allowing a microbiological cure and a favourable clinical outcome. For any tables or figures, please contact the authors directly

Aim. While 16S rRNA PCR - Sanger sequencing has paved the way for the diagnosis of culture-negative bacterial infections, it does not provide the composition of polymicrobial infections. We aimed to evaluate the performance of the Nanopore-based 16S rRNA metagenomic approach using partial-length amplification of the gene, and to explore its feasibility and suitability as a routine diagnostic tool for bone and joint infections (BJI) in a clinical laboratory. Method. Sixty-two clinical samples from patients with BJI were sequenced on MinION* using the in-house partial amplification of the 16S rRNA gene. BJI were defined based on the ICM Philly 2018 and EBJIS 2021 criteria. Among the 62 samples, 16 (26%) were culture-positive, including 6 polymicrobial infections, and 46 (74%) were culture-negative from mono- and polymicrobial infections based on Sanger-sequencing. Contamination, background noise definition, bacterial identification, and time-effectiveness issues were addressed. Results. Results were obtained within one day. Setting a threshold at 1% of total reads overcame the background noise issue and eased interpretation of clinical samples. The partial 16S rRNA metagenomics approach had a greater sensitivity compared both to the culture method and the Sanger sequencing. All the 16 culture-positive samples were confirmed with the metagenomic sequencing. Bacterial DNA was detected in 32 culture-negative samples (70%), with pathogens consistent with BJI. The 14 Nanopore negative samples included 7 negative results confirmed after implementation of other molecular techniques and 7 false-negative MinION results: 3 Kingella kingae infections detected after targeted-PCR only, 2 Staphylococcus aureus infections and 2 Pseudomonas aeruginosa infections sterile on agar plate media and detected only after implementation of blood culture media, advocating for the very low inoculum. Conclusions. The results discriminated polymicrobial samples, and gave accurate bacterial identifications compared to Sanger-based results. They confirmed that Nanopore technology is user-friendly as well as cost- and time-effective. They also indicated that 16S rRNA targeted metagenomics is a suitable approach to be implemented for routine diagnosis of culture-negative samples in clinical laboratories. * Oxford Nanopore Technologies

Aim. Bone and joint infection requires antimicrobial treatment for 6 to 12 weeks. When patients are well prepared and instructed regarding their therapy, they are more likely to have less side effects and improved compliance. Although side effects are common, this coaching is often not routinely performed when oral treatment is given. We developed a monitoring and guidance program for our outpatients who are on long term antimicrobial therapy, in which we can early signal side effects and treatment failure and coach the patients in their journey of infection treatment. Method. In our tertiary referral centre for orthopaedic infections, we started the outpatient monitoring of antimicrobial treatment (OMAT)- team for patients who will receive antimicrobial therapy for >2 weeks. Before discharge, our trained nurse gives instruction to the patient. Within 3 days after hospital discharge the patient is contacted by phone to, if necessary, clarify ambiguities in monitoring set up. During this contact, the nurse checks for side effects, addresses logistic problems regarding laboratory monitoring or future appointments and coaches patients for other questions. The patient is instructed how to recognize and who to contact in case of red flags and problems possibly related to the treatment. This is repeated after every laboratory check-up. Supervision is performed by an infectious disease specialist in close collaboration with the patient's surgeon. Results. The OMAT-team started in October 2020 and consists of 3 trained nurses and 3 ID specialist. In one year, 453 patients were proactively monitored for a mean of 11 weeks. Routinely, laboratory measurements were performed 1 week after the start of therapy and every 3–4 weeks thereafter, which resulted in 2711 contacts per year. In total, 64% of the patients reported side effects and 13% needed one or more extra laboratory measurement. This led to 40 additional outpatient consultations by the ID specialist because of complications of treatment and a switch of the antimicrobial agent in 31% of the patients. Conclusions. OMAT seems to improve the early signalling of complications regarding treatment, which is likely to improve compliance. The OMAT-team serves as a easy to access team to discuss any problem regarding antimicrobial therapy. Being proactive, the OMAT-team intervenes in an early stage of problems regarding side effects, logistics of the treatment and possible treatment failure. Future analysis of our data will show to what extend this will lead to prevention of re-hospitalization and improvement of success rate

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

Aim. At our tertiary orthopaedic centre, mycobacterial cultures are routinely performed on bone and joint samples sent for bacterial culture. We have previously described the prevalence Mycobacterium tuberculosis Complex (MTBC) in these samples. Here, we describe the prevalence of non-tuberculous mycobacteria (NTM). We calculate the number needed to test to identify one previously undiagnosed mycobacterial bone or joint infection. Methods. Samples taken during a single procedure were pooled in one BACTEC MGIT culture. From laboratory records, we ascertained the number of mycobacterial cultures performed, the number positive for MTBC or NTM, and characteristics of individuals from whom mycobacteria were isolated. We collected the same data from 100 individuals with negative mycobacterial cultures. Results presented here are from interim analysis. Results. Excluding sample types that were clearly not bone or joint samples, 6162 mycobacterial cultures were performed between 4 July 2017 and 30 September 2022. Twenty-two patients had MTBC and 6 patients had NTM newly isolated from bone or joint samples placed in mycobacterial culture, with a further patient having both M. tuberculosis and M. avium isolated. In both patients with M. abscessus, the organism also grew in routine bacterial cultures. In one further patient, M. fortuitum was isolated from a sample not put into mycobacterial culture. To identify one new mycobacterial infection of bone or joint (MTBC or NTM) that would not be detected with routine bacterial cultures, 228 (95% CI 157 – 346) mycobacterial cultures were needed. The laboratory cost per additional patient identified using MGIT cultures was €12,540 (95% CI €8,635 - €19,030). Mycobacterial cultures were much less likely to be positive in samples taken from prosthetic joints. They were more likely to be positive in spinal samples and in samples taken from patients with suspected sarcoma. In patients for whom we had contemporaneous histological specimens, these demonstrated granulomatous inflammation in 86% (18/21) of patients from whom MTBC had been isolated but in neither of the two patients from whom only NTM was isolated. Ascertaining the clinical significance of NTM isolates is challenging, although in 2/8 cases the same organism was isolated following repeat sampling. Conclusions. Targeted rather than routine mycobacterial culture of bone and joint specimens should be considered in settings with a low burden of tuberculosis. NTM are rarely isolated from bone and joint specimens at our centre and fast growers may be isolated using routine bacterial culture

Aim. There are no studies in literature that analyze the effectiveness of closed-incisional negative pressure wound therapy (ciNPWT) in the treatment of bone and joint infections (BJI). The aim of the study was to evaluate the efficacy and the safety of the application of ciNPWT in the postsurgical wound management of patients with osteoarticular infections. Method. We conducted a perspective single-center study on patients with BJI treated between 01/2022 and 10/2022 with ciNPWT dressing application at the end of the surgical procedure. All patients were treated by a multidisciplinary team (MDT) approach and operated by the same surgical equipe. Inclusion criteria were: presence of periprosthetic joint infection (PJI), fracture-related infection (FRI), osteomyelitis (OM), septic arthritis (SA) surgically treated, after which ciNPTW was applied over the closed surgical wound. 30 patients (19M, 11F) have been analyzed with mean age of 56,10±17,11 years old; BJIs were all localized in the lower limb (16 PJI, 12 FRI, 1 SA, 1 OM). Results. We considered the following clinical local pre-operative parameters: presence of fistula (10 patients, 33,33%), presence of erythema (18 patients, 60%), presence of previous flap in the incisional site (7 patients, 23,33%). In 11 cases (36,67%) more than 3 previous surgical procedures were performed in the surgical site. The following surgical procedures were performed: 8 debridement and implants removal, 7 DAIR, 3 one-stage exchange, 6 two-stage exchange, 3 spacer exchange, 3 resection arthroplasty. Nineteen patients (63,34%) showed no occurrence of any local post-operative complication (erythema, hematoma, wound breakdown, wound blister, necrosis). Seven (23,33%) patients showed the presence of one or more postoperative complications that didn't require additional surgery. We observed four (13,33%) failures, defined as the need for further surgical procedures following the onset of a local complication: two patients had a wound breakdown before wound closure and two had a recurrence of infection after an uneventfully wound closure. All failures were within the group of joint infection (PJI+SA) and were affected by a multi drug resistant pathogen. Conclusions. In our series four patients required further surgery, but only two cases were related to incisional wound problems, that is consistent with aseptic joint revision surgeries data that are available in literature (3.4%-6.9%)[1-2]. Patients affected by BJI are a group with significant high risk of failure and therefore the use of ciNPWT should be considered. However, randomized clinical trials are needed to establish the superiority of the ciNPWT dressing over the standard one

Aim. Culture negative (CN) prosthetic joint infections (PJI) account for approximately 10% of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJI within a large prospective cohort study, and to compare their characteristics and outcomes with culture positive cases. Methods. The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, binational, multicentre observational cohort study conducted at 27 hospitals between July 2014 and December 2017. We compared baseline characteristics and outcomes of all patients with culture negative (CN) prosthetic joint infection (PJI) from the PIANO cohort with culture positive (CP) cases. “Treatment success” was defined as absence of clinical or microbiological signs of infection, no need for ongoing antibiotics, and no need for revision or resection arthroplasty since the end of the initial treatment. We also describe PJI diagnostic criteria in the CN cohort and apply internationally recognised PJI diagnostic guidelines. Results. Of the 650 patients eligible for inclusion, 55 (8.5%) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female [32 (58.2%) vs 245 (41.2%); p=0.02], involve the shoulder joint [5 (9.1%) vs. 16 (2.7%); p=0.03] and have a lower mean C-reactive protein (142 mg/L vs. 187 mg/L; p=0.02). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (aOR 3.78; 95%CI 1.65 – 8.67). Of the 55 CN cases meeting Infectious Diseases Society of America (IDSA) diagnostic criteria, 45 (82%) met European Bone and Joint Infection Society (EBJIS) criteria (probable or definite) and 39 (71%) met the 2013 Musculoskeletal Infection Society (MSIS) criteria. Conclusions. Culture negativity is an independent predictor of treatment success in PJI. It is unclear whether this is because some of them are not actually infections, or for other reasons such as lower bacterial load or earlier effective antibiotic treatment. Diagnostic criteria for PJI vary substantially in their sensitivity, with MSIS criteria being the least sensitive. Acknowledgements. This work is being presented on behalf of the broader PIANO investigators and the Australasian Society for Infectious Diseases Clinical Research Network. The PIANO study received seed funding from Heraeus Medical and the John Hunter Hospital Charitable Trust Fund

Aim. Serum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP). Method. From January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC). Results. A total of 275 patients with rTHA and rTKA were included, 144 joints (52.4%) were identified as septic. Decreased AGR and elevated CRP were strongly associated with PJI, optimal diagnostic thresholds were calculated with 1.253 and 9.4 mg/L, respectively. Sensitivities were 62.5% (95%-confidence interval: 54.3–70.0) and 73.6% (65.8–80.1), and specificities 84.7% (77.5–89.9) and 87.8% (80.9–92.4), respectively. CRP showed a significantly higher AUC than AGR (0.807 (0.761–0.853) and 0.736 (0.686–0.786); p<0.0001). Subgroup analysis of acute versus chronic infections yielded significantly higher diagnostic accuracies in acute PJI for both parameters (p<0.0001). Similar results were observed when focusing on the causative microorganism; a better diagnostic performance was observed in high-virulence PJI compared to low-virulence PJI (p≤0.005). Furthermore, higher AUCs were calculated in knee PJI compared with hip PJI, with a significant difference for AGR (p=0.043). Conclusions. Due to its limited diagnostic accuracy, serum AGR cannot be recommended as an additional marker for diagnosing PJI. Serum parameters are generally unspecific and can be influenced by comorbidities and other foci of infection. Additionally, parameters may remain within normal levels in low-grade PJI. Evaluating AGR, further possible pitfalls must be considered, for example an increased latency until bottom values are reached and the impact of malnutrition

Aim. Dalbavancin is a lipoglycopeptide with a half-life of 14 days (range 6.1 to 18.4), significantly longer than other antimicrobials, which avoids the need for daily antibiotic dosing. This multi-centre observational study aims to describe the use of dalbavancin to facilitate discharge in treating bone and joint infections. Method. All adult patients treated with dalbavancin from January 2017 to September 2022 in four UK bone infection units were included. Data collected through a standardised data collection form included:. Clinical and microbiological characteristics. Hospital length of stay. Complications. Patient suitability for hypothetical treatment options, such as Outpatient Parenteral. Antibiotic Team (OPAT). Clinical outcome. Treatment-related costs were calculated for dalbavancin and the preferred hypothetical treatment option that would have been administered for the same duration. The costs were subtracted to calculate the cost difference. Clinical success was defined as the absence of definite failure in accordance with the OVIVA Trial protocol. Results. Thirty-six patients were included: 20 males and 16 females, with a median age of 53 (IQR 43–73): Thirteen were septic arthritis, twelve were prosthetic joints, seven were spondylodiscitis and five were other orthopaedic-related implant infections. In twenty cases the infecting organism was Staphylococcus aureus, fourteen were due to coagulase-negative staphylococci and two no cultured organism. Reasons for dalbavancin. The reasons for choosing dalbavancin over alternatives were due to either:. Necessity due to poor adherence (21), or lack of viable OPAT options due to antibiotic resistance or intolerance (7). OR. Convenience to avoid the need for OPAT (8). Dalbavancin was initiated at 1500mg after a median of 12 days (IQR 6–17) of in-hospital antimicrobial therapy. Subsequent dalbavancin doses were based on clinical decisions and ranged from 1000mg to 1500mg. Healthcare benefits. Switching to dalbavancin reduced treatment costs by a median of £3526 (IQR 1118 - 6251) compared with the preferred theoretical alternatives. A median of 31 hospital days (IQR 23–47) was avoided among patients who would have required a prolonged inpatient stay. Outcome. Overall, 20 patients (55.6%) were successfully treated after a median follow-up of 8 months (IQR, 5.8 – 18.4). No patients developed an adverse drug reaction. Conclusions. Dalbavancin can safely facilitate outpatient treatment in patients with limited oral options and in whom OPAT is unsuitable. Dalbavancin is cost-effective compared with the alternative of an inpatient stay

Aim. Bone and joint infections (BJIs) are serious infections requiring early optimized antimicrobial therapy. BJIs can be polymicrobial or caused by fastidious bacteria, and the patient may have received antibiotics prior to sampling, which may decrease the sensitivity of culture-based diagnosis. Furthermore, culture-based diagnosis can take up to 14 days. Molecular approaches can be useful to overcome these concerns. The BioFire® system performs syndromic multiplex PCR in 1 hour, with only a few minutes of sample preparation. The BioFire® Joint Infection (JI) panel (BF-JI), recently FDA-cleared, detects both Gram-positive (n=15) and Gram-negative bacteria (n=14), Candida, and eight antibiotic resistance genes directly from synovial fluids. The aim of this study was to evaluate its performance in acute JIs in real-life conditions. Method. BF-JI was performed on synovial fluid from patients with clinical suspicion of acute JI, either septic arthritis or periprosthetic JI, in 6 French centers. The results of BF-JI were compared with the results of culture of synovial fluid and other concomitantly collected osteoarticular samples obtained in routine testing in the clinical microbiology laboratory. Results. From July 2021 to May 2022, 319 patients (including 10 children < 5y and 136 periprosthetic infections) had been included in the study. The BF-JI test was invalid for one patient (not retested). Among the 318 remaining patients, overall concordance with comparative microbiology methods was 88% (280/318): 131 samples were negative with both BF-JI and culture, and 149 samples were positive with the same microorganisms using complementary techniques. In 33 cases (10.4%), BF-JI was negative while culture was positive: 18 microorganisms were not targeted by BF-JI (including Staphylococcus epidermidis, n=10, and Cutibacterium acnes, n=2); 15 microorganisms targeted by BF-JI were obtained in culture but not by the molecular test (false-negative 4.7%). In 20 cases, BF-JI was positive while culture was not: 12 patients had received antibiotics before sampling, and 7 cases involved fragile and fastidious bacteria (Kingella kingae, n=5; Neisseria gonorrhoeae, n=2). In 6 cases, both BF-JI and culture were positive, but no yielding the same bacteria (polymicrobial specimens). Conclusions. In acute JIs, the BF-JI panel shows a good concordance with culture for the microorganisms targeted by the panel. Therefore, this molecular tool may have a place in microbiological diagnosis of acute JIs in order to confirm JI faster than culture. Moreover, it allows easy detection of difficult-to-culture bacteria. Acknowledgements. study was supported by bioMérieux, who provided all reagents

Aim. Recurrence of bone and joint infection, despite appropriate therapy, is well recognised and stimulates ongoing interest in identifying host factors that predict infection recurrence. Clinical prediction models exist for those treated with DAIR, but to date no models with a low risk of bias predict orthopaedic infection recurrence for people with surgically excised infection and removed metalwork. The aims of this study were to construct and internally validate a risk prediction model for infection recurrence at 12 months, and to identify factors that predict recurrence. Predictive factors must be easy to check in pre-operative assessment and relevant across patient groups. Methods. Four prospectively collected datasets including 1173 participants treated in European centres between 2003 and 2021, followed up to 12 months after surgery for orthopaedic infections, were included in logistic regression modelling [1–3]. The definition of infection recurrence was identical and ascertained separately from baseline factors in three contributing cohorts. Eight predictive factors were investigated following a priori sample size calculation: age, gender, BMI, ASA score, the number of prior operations, immunosuppressive medication, glycosylated haemoglobin (HbA1c), and smoking. Missing data, including systematically missing predictors, were imputed using Multiple Imputation by Chained Equations. Weekly alcohol intake was not included in modelling due to low inter-observer reliability (mean reported intake 12 units per week, 95% CI for mean inter-rater error −16.0 to +15.4 units per week). Results. Participants were 64% male, with a median age of 60 years (range 18–95). 86% of participants had lower limb orthopaedic infections. 732 participants were treated for osteomyelitis, including FRI, and 432 for PJI. 16% of participants experienced treatment failure by 12 months. The full prediction model had moderate apparent discrimination: AUROC (C statistic) 0.67, Brier score 0.13, and reasonable apparent calibration. Of the predictors of interest, associations with failure were seen with prior operations at the same anatomical site (odds ratio for failure 1.51 for each additional prior surgery; 95% CI 1.02 to 2.22, p=0.06), and the current use of immunosuppressive medications (odds ratio for failure 2.94; 95% CI 0.89 to 9.77, p=0.08). Conclusions. This association between number of prior surgeries and treatment failure supports the urgent need to streamline referral pathways for people with orthopaedic infection to specialist multidisciplinary units

Aim. Patient quality of life (QoL) in untreated bone infection was compared to other chronic conditions and stratified by disease severity. Method. Patients referred for treatment of osteomyelitis (including fracture related infection) were identified prospectively between 2019 and 2023. Patients with confirmed infection completed the EuroQol EQ-5D-5L questionnaire. Clinicians blinded to EQ-index score, grouped patients according to JS-BACH Classification into ‘Uncomplicated’, ‘Complex’ or ‘Limited treatment options’. A systematic review of the literature was performed of other conditions that have been stratified using EQ-index score. Results. 257 patients were referred, and 219 had suspected osteomyelitis. 196 patients had long bone infection and reported an average EQ-index score of 0.455 (SD 0.343). 23 patients with pelvic osteomyelitis had an average EQ-index score of 0.098 (SD 0.308). Compared to other chronic conditions, patients with long-bone osteomyelitis had worse QoL when compared to different types of malignancy (including bladder, oropharyngeal, colorectal, thyroid and myeloma), cardiorespiratory disease (including asthma, COPD and ischaemic heart disease), psychiatric conditions (including depression, pain and anxiety), endocrine disorders (including diabetes mellitus), neurological conditions (including Parkinson's disease, chronic pain and radiculopathy) and musculoskeletal conditions (including osteogenesis imperfecta, fibrous dysplasia and x-linked hypophosphataemic rickets). QoL in long-bone infection was similar to conditions such as Prada-Willi syndrome, Crohn's disease and juvenile idiopathic arthritis. Patients who had a history of stroke or multiple sclerosis reported worse QoL scores compared to long-bone infection. Patients who had pelvic osteomyelitis gave significantly lower QoL scores when compared to all other conditions that were available for comparison in the literature. In long bone infection, 41 cases (21.0%) were classified as ‘Uncomplicated’, 136 (69.4%) as ‘Complex’ and 19 (9.7%) as ‘Limited treatment options available’. Within classification stratification, patients with ‘Uncomplicated’ long bone infections reported a mean EQ-index score of 0.618 (SD 0.227) which was significantly higher compared to ‘Complex’ (EQ-index: 0.410 SD 0.359, p=0.004) and ‘Limited treatment options available’ (EQ-index: 0.400 SD 0.346, p=0.007). Conclusions. Bone and joint infections have a significant impact on patient quality of life. It is much worse when compared to other common chronic conditions, including malignancy, cardiovascular and neurological diseases. This has not been previously reported but may focus attention on the need for more investment in this patient group

Aim. Vancomycin is frequently used for bone and joint infections (BJI) because of the main role of Gram-positive bacteria as potential causal agents. It is crucial to achieve optimal vancomycin plasma concentrations since the first day to maximize treatment clinical and microbiological efficacy. The aim was to describe the patients’ profile that are more likely to achieve an optimal pharmacokinetic/pharmacodynamics (PK/PD) vancomycin target in the first therapeutic drug monitoring (TDM) sample. Methods. Retrospective study (March 2018-January 2022) in a university hospital including all patients treated with vancomycin for a BJI and undergoing TDM. Initial dose (1g/8-12h) was selected by the responsible clinician. Vancomycin plasma concentrations were obtained pre-dose (Cmin,ss) and 60-minutes after the infusion on day 2 of treatment. Global exposure measured by the area under the curve of plasma concentrations during 24h (AUC024h) was estimated using a bicompartmental PK model. An AUC024h/CMI=400–600mg*h/L was considered optimal, <400 infratherapeutic and >600 supratherapeutic, based on recent guidelines, and patients were classified into these 3 groups. A value of CMI=1 mg/L was considered, following guidelines recommendations. Categorial data: percentages and quantitative data as mean (standard deviation). Results. Ninety-five patients were included: 22(23.2%), 43(45.3%) and 30(31.6%) presented an infratherapeutic, optimal and supratherapeutic PKPD target, respectively. Medium age was 75,8(13,5) in the supratherapeutic group versus 57,2(16,3) in the infratherapeutic group. Weight (kg) was higher in the infratherapeutic group 80,8(18,4) versus 66,8(15,5) in the supratherapeutic group. Vancomycin dose (mg/kg/d) was 43,5(12,4) in the supratherapeutic group versus 34,5(10,8) in the infratherapeutic group. There were 17(56,7) patients who received 1g/8h of vancomycin in the supratherapeutic group and 6 (27,3) in the infratherapeutic group. Baseline glomerular filtration rate (BGF (CKD-EPI) (mL/min/1.73m2) was 71,5(20,1) in the supratherapeutic group and 100,0 (19,9) in the infratherapeutic group. The AUC24h/CMI was 788,0(186,1) in the supratherapeutic group and 323,7(55,4) in the infratherapeutic group. Significant differences observed in age, body weight (BW), baseline renal function and dose/frequency of vancomycin. Dosage adjustments recommendations were made in 62(65.3%) patients: 31(32.6%) dose-increase, 29(30.5%) reduction and 2 cases (2.1%) a temporary suspension. Conclusions. Less than 50% of patients achieved an optimal exposure of vancomycin on day 2 of treatment. Patients with infratherapeutic levels had a younger age and a higher body weight and glomerular filtration rate. In addition, they had received a lower vancomycin initial dose. On the contrary, a potentially toxic exposure was observed within older patients with impaired baseline renal function. These data suggest the relevance of an early vancomycin TDM for optimizing the treatment of BJI

Aim. Sepsis is a life-threatening complication of periprosthetic joint infections (PJI) that requires early and effective therapy. This study aims to investigate the epidemiology, associated risk factors, and outcome of sepsis in the context of periprosthetic joint infections (PJI). Method. This single-center retrospective cohort study included patients treated for PJI from 2017 to 2020. Patients were classified based on the criteria of the European Bone and Joint Infection Society. The presence of sepsis was determined using the SOFA score and SIRS criteria. The cohort with PJI and sepsis (sepsis) was compared to patients with PJI without sepsis (non-sepsis). Risk factors considered were patient characteristics, affected joints, surgical therapy, microbiological findings, preexisting medical conditions, clinical symptoms, and symptom duration. Outcome parameters were mortality, length of hospital stay, and length of stay in the intensive care unit. Results. A total of 109 patients with PJI were identified, of whom 45 patients (41.3%) met the criteria for sepsis. Patients with sepsis had more severe preexisting diseases compared with the non-sepsis cohort (Charlson Comorbidity Index 3.8 vs. 2.8; p≤0.001). An increased odds ratio (OR) for a septic course was found for the comorbidities pneumonia (8.2; p=0.001), myocardial infarction (2.0; p=0.02), atrial fibrillation (3.3; p=0.01), diabetes mellitus (1.2; p=0.04), endocarditis (5.5; p=0.01), and renal disease (2.0; p≤0.001). Infection with Staphylococcus aureus (sepsis 20 vs. non-sepsis 10; p=0.002), Streptococcus dysgalactiae (sepsis 7 vs. non-sepsis 2; p=0.002) and Candida albicans (sepsis 5 vs. non-sepsis 0; p=0.01) were more prevalent in patients with sepsis. In the sepsis cohort, further infectious foci were present in addition to PJI in 57.8% of patients, compared to 18.8% in the non-sepsis cohort. The presence of sepsis was associated with a longer hospital stay (sepsis 68 days vs. non-sepsis 38 days; p=0.001) and longer intensive care unit stay (sepsis 12 days vs. non-sepsis 2 days; p=0.001). In-hospital mortality was ten times higher in the sepsis cohort compared to non-septic patients (sepsis 11/42 vs. non-sepsis 2/64; OR 10.3; p=0.01). Conclusions. In a relevant proportion of patients, PJI can lead to a septic course of disease associated with increased mortality. Particularly in patients with preexisting diseases, increased attention is required, and comprehensive screening for other foci of infection seems mandatory. In addition to highly virulent pathogens such as staphylococci and streptococci, fungal infections should be considered as causative pathogens in septic patients with PJI

Aims. Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI. Methods. A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared. Results. Using the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001). Conclusion. With high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods. Cite this article: Bone Joint Res 2021;10(8):536–547

Aims. Current guidelines consider analyses of joint aspirates, including leucocyte cell count (LC) and polymorphonuclear percentage (PMN%) as a diagnostic mainstay of periprosthetic joint infection (PJI). It is unclear if these parameters are subject to a certain degree of variability over time. Therefore, the aim of this study was to evaluate the variation of LC and PMN% in patients with aseptic revision total knee arthroplasty (TKA). Methods. We conducted a prospective, double-centre study of 40 patients with 40 knee joints. Patients underwent joint aspiration at two different time points with a maximum period of 120 days in between these interventions and without any events such as other joint aspirations or surgeries. The main indications for TKA revision surgery were aseptic implant loosening (n = 24) and joint instability (n = 11). Results. Overall, 80 synovial fluid samples of 40 patients were analyzed. The average time period between the joint aspirations was 50 days (SD 32). There was a significantly higher percentage change in LC when compared to PMN% (44.1% (SD 28.6%) vs 27.3% (SD 23.7%); p = 0.003). When applying standard definition criteria, LC counts were found to skip back and forth between the two time points with exceeding the thresholds in up to 20% of cases, which was significantly more compared to PMN% for the European Bone and Joint Infection Society (EBJIS) criteria (p = 0.001), as well as for Musculoskeletal Infection Society (MSIS) (p = 0.029). Conclusion. LC and PMN% are subject to considerable variation. According to its higher interindividual variance, LC evaluation might contribute to false-positive or false-negative results in PJI assessment. Single LC testing prior to TKA revision surgery seems to be insufficient to exclude PJI. On the basis of the obtained results, PMN% analyses overrule LC measurements with regard to a conclusive diagnostic algorithm. Cite this article: Bone Jt Open 2021;2(8):566–572

Aims. Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI. Methods. From 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined. Results. Eradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures). Conclusion. Therapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results. Cite this article: Bone Jt Open 2021;2(8):671–678

Aim. The aim of this study was to confirm that Mirra's criterion (≥ 5 Polymorphonuclears (PMNs) per field in 5 high power fields (HPFs)) is not adequate for diagnosis of chronic bone and joint infections (BJIs) due to Cutibacterium acnes (C. acnes). The second objective was to determine if plasma-cell infiltration, that is a classical marker of chronic inflammation, could be useful for the diagnosis of chronic BJIs due to C. acnes. Methods. We retrospectively selected 25 patients from 2009 to 2013 with chronic BJIs due to C. acnes. In addition of Mirra's criterion, the number of plasma-cells (≥5 plasma-cells/5 HPFs, defined as “CRIOAc Lyon's criterion”) was implemented in the histopathological analysis. Patients were defined as infected, if at least one of the two criteria were present. Results. According to Mirra's and CRIOAc Lyon's histopathological criteria, positive histology was observed in respectively 12 (48%) and 16 (64%) cases. In 1 case the samples were not analyzable. Considering the 12 cases with negative Mirra's criterion, high plasma-cell infiltration (≥5 plasma-cells/5 HPFs; Figure 1) was observed in 6 cases (50%), and low plasma-cells infiltration (2–5 plasma-cells/5 HPFs) was observed in 5 other cases (42%). Conclusions. Mirra's criterion is not an adequate criterion to defining chronic BJIs [1, 2]. In our study, more cases of chronic BJIs due to C. acnes have been diagnosed using CRIOAc Lyon's criterion than Mirra's criterion. Adding CRIOAc Lyon's criterion might restore some histopathological diagnosis of chronic BJIs due to C. acnes, when a clinical chronic BJI is suspected. For any tables or figures, please contact the authors directly

Aim. Bone and implant-associated infections caused by microorganisms that grow in biofilm are difficult to treat because of persistence and recurrence. Systemic administration of antibiotics is often inefficient because the poor vascularization of the site of infection. This issue has led to the development of biomaterials capable to locally deliver high doses of therapeutic agents to the injured bone with minimal systemic effects. In this context, calcium sulphate/hydroxyapatite (CS/HA) bone graft substitutes are widely used being safe, osteoconductive and resorbable biomaterials that can be easily enriched with consistent amounts of antibiotics. In this in vitro study, the capability of the eluted antibiotics to select the tested bacterial strains for antibiotic resistance was evaluated to confirm the safe use of the product. Method. S. aureus, S. epidermidis and P. aeruginosa isolated in our Institute from bone and joint infection with different resistance phenotypes were used. 6 × 2.5 mm CS/HA discs were generated by pouring the antibiotic loaded formulations in a mold and were used as a modified disk diffusion test. The resistance selection was evaluated by subculturing cells growing on the edge of the zone of inhibition (ZOI) for seven days. Minimum inhibitory concentrations (MICs) of gentamicin and vancomycin were determined by broth microdilution method before and after the selection of resistance assay. In addition, MICs were assessed after seven day passage on antibiotic free agar plates to evaluate if eventual decrease of antibiotic susceptibility was stable or only transient. Results. Commonly, no adaptation in presence of both CS/HA formulations was observed by analysing ZOI on agar medium. The kinetic of decrease of the ZOI was similar between the strains, with the exception of gentamicin resistant staphylococci in presence of gentamicin loaded CS/HA, which was faster with respect to the susceptible strains. Conclusions. The present study shows that elution of gentamicin and vancomycin from CS/HA bone graft substitutes did not induce a decrease in susceptibility to these antibiotics in an in vitro setting, suggesting the safe use of the product

Aim. Our goal is to assess diagnostic accuracy of synovial fluid testing in diagnosing prosthetic joint infection (PJI) as defined by the European Bone and Joint Infection Society (EBJIS). In addition to differential leukocyte count, simples and inexpensive biomarkers such as synovial fluid C-reactive protein (CRP), adenosine deaminase (ADA) and alpha-2-macrogloblulin(A2M) were also investigated and its possible role in increasing accuracy assessed. Method. Between January/2013 and December/2019 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples, as well as the implant for sonication, were gathered for microbiological study. Definitive diagnosis was classified according to the new EBJIS PJI definition. Using receiver operating characteristic curves, we determined cutoff values as well as diagnostic accuracy for each marker. Results. Out of 364 revision arthroplasties performed, 102 fully respected inclusion criteria. There were 58 unlikely, 8 likely and 36 confirmed infections. Synovial fluid total leukocyte count, proportion of polymorphonuclear neutrophils (PMN), CRP, ADA and A2M were significantly different between groups. Area under the curve was 0.94 for total leucocyte count, 0.91 for proportion of PMN, 0.90 for CRP, 0.82 for ADA and 0.76 for A2M. Sensitivity, specificity, and predictive values for statistically optimal but also selected rule-in and rule-out cutoffs values are shown in Table 1. Interpreting a raised level of CRP(>2.7mg/L) or ADA(>60U/L) together with high leukocyte count (>1470 cells/μL) or proportion of PMN (>62.5%) significantly increases specificity and positive predictive value for affirming PJI. Conclusions. Differential leukocyte count cutoffs proposed by the EBJIS PJI definition are shown to perform well in ruling out (<1,500 cells/μL) and ruling in (>3,000 cells/μL) PJI. Adding simple and inexpensive biomarkers such synovial CRP or ADA is helpful in interpreting inconclusive results. For any tables or figures, please contact the authors directly

Aim. Prosthetic joint infections (PJI) and fracture related infections (FRI) are the most challenging complications in orthopaedic surgery. An interdisciplinary approach is mandatory not only to correctly diagnose and treat major musculoskeletal infections but also to address the comorbidities and impairments these patients are not rarely suffering from. Since, little data exists on cardiac complications following PJI and FRI revision surgery, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality. Method. We prospectively included consecutive patients at high cardiovascular risk (defined as expected postoperative hospital stay of >24 hours PLUS age >45 years with pre-existing coronary, peripheral or cerebrovascular artery disease OR age >65 years) undergoing major orthopaedic surgery between 2014 and 2016. All patients received a systematic screening to reliably detect PMI, using serial measurements of high-sensitivity cardiac troponin T (hs-cTnT). All-cause mortality was assessed at 30 days and one year. Multivariable logistic regression models were applied to compare incidence of PMI and mortality between patients undergoing septic revision surgery (for PJI/FRI) and patients receiving aseptic major bone and joint surgery. Results. In total 911 consecutive patients, with an overall PMI rate of 15.4% (n=140) were included. The PMI incidence in patients undergoing septic revision surgery was significantly higher compared to aseptic orthopaedic surgeries (29.2% vs 14.3%, p=0.001), also after multivariable adjustment (odds ratio 2.1, p=0.02). Mortality was higher at one year (16.9% vs. 8.3%, p=0.037) and numerically at 30 days (6.2% vs. 2.4%, p=0.085) in patients undergoing septic revision surgery. Virulence of the disease-causing pathogen showed no significant relationship with PMI incidence or mortality. Conclusions. Patients undergoing revision surgery for PJI or FRI were at a distinct higher risk of PMI and death compared to matched non-septic patients. In major bone and joint infections screening for PMI and treatment in specialized multidisciplinary units should be considered

Aim. Bone and Joint Infections (BJIs) present with non-specific symptoms and can be caused by a wide variety of bacteria and fungi, including many anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians currently rely primarily on culture to identify the pathogen(s) responsible for infection. The BioFire. ®. FilmArray. ®. Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) was designed to detect 15 gram-positive (seven anaerobes), 14 gram-negative bacteria (one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel (BBJIP) compared to conventional used as reference methods. Method. In a monocentric study, leftover synovial fluid specimens were collected in a single institution including 4 hospitals and tested using conventional bacterial culture (Standard of Care (SoC)) according to routine procedures following French national recommendations. Specimen has been placed in a refrigerator (4°C) as soon as possible after collection and stored for less than or equal to 7 days before enrollment. Performance of the IUO version of the BBJIP was determined by comparison to SoC for species identification. Results. To date, 201 specimens have been collected and tested using BBJIP. A total of 39 pathogens were obtained in culture. Compared to SoC culture, the overall PPA was 89.7% (35 TP, 4 FN (SA, 1; Strepto Spp, 2; P. micra, 1) and the overall NPA was 99.7% with 16 FP for a total of 5374 bacterial targets screened. Two complementary molecular tests using home-made PCR are underway to definitively conclude about the FN et FP for BBJIP observed in the preset study. Conclusions. The BioFire BJI Panel appears as a promising, sensitive, specific, and robust test for rapid detection of 31 microorganisms (including anaerobes) and eight AMR genes in synovial fluid specimens. The number of pathogens and resistance markers included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the management of BJIs

Aim. The diagnosis of prosthetic joint infection (PJI) is challenging and relies on a combination of parameters. However, the currently recommended diagnostic algorithms have not been validated for patients with recent surgery, dislocation or other events associated with a local inflammatory response. As a result, these algorithms are not safely applicable offhand in such conditions. Calprotectin is a leukocyte protein that has been shown to be a reliable biomarker of PJI. The purpose of this study was to evaluate the use of calprotectin to rule out PJI within 3 months after surgery or dislocation. Method. We included patients who underwent arthroplasty revision surgery at our institution within 3 months after any event causing inflammation. Calprotectin was measured using a lateral-flow assay. European Bone and Joint Infection Society (EBJIS) criteria were used as gold standard. The diagnostic accuracy of calprotectin was calculated. Results. Twenty-two patients (14 females, 8 males) with a mean age of 65.1 ± 12.3 years with 13 total hip (THA) and 9 total knee arthroplasties (TKA) were included. There were 4 instances of possible early-onset acute infection, 4 dislocations, 2 patella tendon ruptures, 1 local tissue reaction to the sutures, 4 cases of early loosening, 2 component breakages and 1 avulsion of a polyethylene patella button. Using the EBJIS criteria, PJI was confirmed postoperatively in 12 cases. With a cut-off at 50mg/L, the calprotectin lateral flow test was positive in 10 cases. This results in a sensitivity of the calprotectin test of 0.75, a specificity of 0.9, positive and negative predictive values of 0.9 and 0.75, respectively, and a positive and negative likelihood ratio of 7.5 and 0.28, respectively. Conclusions. Aggravating the difficulties of ruling out PJI prior to revision surgery, local inflammation can be caused by some conditions in which the widely accepted PJI definition criteria cannot be applied. Nevertheless, an accurate diagnosis of PJI is just as crucial in these situations as it is in planned revision surgery. This study suggests that calprotectin is a promising diagnostic parameter for ruling out PJI in such cases. The calprotectin lateral-flow assay is readily applicable at the beginning of the procedure, yielding results that can assist in the decision whether to perform septic revision or aseptic partial or component exchange within 15 minutes, and with an overall accuracy of 81.8%

Aim. Bacteriophages, viruses specific of bacteria, are receiving substantial attention as alternative antibacterial agents to treat bacteria frequently multi-resistant to antibiotics and/or able to form biofilms, such as staphylococci. The latter are responsible for very difficult to treat bone and joint infections (BJIs). In this context, our consortium aims to develop a production of therapeutic phages in accordance with the will of ANSM (French National Agency for the Safety of Medicines and Health Products) to encourage the development of a national academic platform for phage therapy. We report the isolation and characterization of new anti-Staphylococcus phages as well as the evaluation of their activity on a collection of clinical strains of S. aureus (SA) and coagulase-negative staphylococci (CNS) in order to assess their therapeutic potential. Method. Seventeen phages were isolated from wastewater samples. Their identification was obtained by Illumina whole genome sequencing. To evaluate their spectrum of activity, 30 genetically characterized SA strains representative of the main genetic backgrounds as well as 32 strains belonging to 7 CNS species responsible for BJIs were included. The spot test technique, based on the determination of the Efficiency Of Plating ratio, was used (EOP, ratio between the phage titer obtained on a tested strain/titer on a reference strain, close to 1 if high sensitivity to the phage). Results. All isolated phages belonged to the Myoviridae family: 14/17 and 3/17 to the Kayvirus and Silviavirus genera respectively. Silviavirus phages were more active on SA strains (EOP>0.001 for 73–90% of strains) than Kayvirus phages (EOP>0.001 for 13–70% of strains, except for V1SA21: 80%). In total, 83% of strains were susceptible to the phage with the broadest spectrum in each genus, their combination representing a promising opportunity to prevent the emergence of resistance. Kayvirus phages had polyvalent activity on several CNS species (maximum 47% of tested strains), mainly S. lugdunensis, S. capitis and S. caprae, whereas Silviavirus phages were only active on 6–12% of the tested strains. Conclusions. We report the characterization of a large collection of novel phages with complementary spectra against a collection of SA and CNS strains. Further work is currently focused on i) the isolation of anti-S. epidermidis phages, bacterial species against which the present collection of phages was insufficiently active, while it is a major pathogen in this context, ii) the development of production and purification protocols in order to meet the requirements of ANSM for human use

Aim. Staphylococcus epidermidis (S. epidermidis) is one of the main pathogens responsible for bone and joint infections especially those involving prosthetic materials (PJI). Although less virulent than S. aureus, S. epidermidis is involved in chronic infections notably due to its ability to form biofilm. Moreover, it is frequently multiresistant to antibiotics. In this context, the development of additional or alternative antibacterial therapies targeting the biofilm is a priority. Method. The aim of this study was to evaluate in vitro the activity of phage lysin exebacase (CF-301) against biofilms formed by 19 S. epidermidis clinical strains responsible for PJI. We determined the remaining viable bacteria inside the biofilm (counting after serial dilution and plating) and the biomass (bacteria and extracellular matrix, using crystal violet staining) after 24h of exposition to exebacase at different concentrations, alone (0.05; 0.5; 5; 50 and 150 mg/L) or in combination (5, 50 and 150 mg/L) with antibiotics commonly used to treat multi-resistant S. epidermidis PJI (rifampin (1 mg/L), vancomycin (10mg/L) and daptomycin (10mg/L)). In this study, synergy was defined as a significantly higher effect of the association in comparison to the sum of the effect of each molecule. Results. Exebacase showed a dose-dependent reduction of biomass, ranging from 11 % at 0.5 mg/L to 66 % at 150 mg/L. Exebacase showed a significant bactericidal activity at 50 and 150 mg/l, with a mean decrease of the inoculum of 0.94 and 1.7 log, respectively. In addition, synergistic effects were observed in association with i) rifampin (1 mg/L) showing a mean decrease up to 84% of the biomass and 3.5 log CFU at 150 mg/L of exebacase, ii) vancomycin (10 mg/L) showing a mean decrease up to 81% of the biomass and 2.82 log CFU at 150 mg/L of exebacase, iii) and daptomycin (10 mg/L) showing a mean decrease up to 85% of the biomass and 3.1 log CFU at 150 mg/L of exebacase. Conclusions. Exebacase showed, in vitro, synergistic activity with antibiotics against S. epidermidis biofilms. It is a promising adjuvant therapy to rifampin, vancomycin and daptomycin in the context of PJI. Further studies are needed, in vitro to understand the mechanism of action on S. epidermidis biofilm and the heterogeneity of strain behaviour and in vivo to confirm the present data

Aim. Several options to standardize the definition of periprosthetic joint infection (PJI) have been created including the 2013 Musculoskeletal Infection Society (MSIS), 2018 Intentional Consensus Meeting (ICM), and the 2019 proposed European Bone and Joint Infection Society (EBJIS) criteria. Synovial fluid biomarkers have been investigated in an effort to simplify and improve the diagnosis of PJI. The aim of this study was to test the sensitivity, specificity, positive, and negative predicted values (PPV and NPV, respectively) of a calprotectin point of care (POC) test for diagnosing PJI in revision total knee arthroplasty (TKA) patients comparing different sets of criteria (2013 MSIS, 2018 ICM, and 2019 EBJIS criteria) used to define patients as with or without infection. Method. From October 2018 to January 2020 and under IRB approval 123 intraoperative samples of synovial fluid were prospectively collected at two academic hospitals in the same institution from revision TKA patients. All patients underwent standard clinical and laboratory evaluation for PJI at our institution, allowing for categorization using the 3 criteria. Patients were adjudicated by 2 blinded and independent reviewers for the 3 sets of criteria. The 3 criteria agreed 91.8% of the time. Four likely cases by the 2019 proposed EBJIS were considered unlikely and 1 inconclusive case by the 2018 ICM was considered not infected for the purposes of analysis. Calprotectin POC testing followed manufacturer's instructions using a threshold of >50 mg/L to indicate PJI. Sensitivities, specificities, PPV, NPV, and areas under the curve (AUC) were calculated for the 3 sets of criteria. Results. Using 2013 MSIS criteria the calprotectin POC test demonstrated a sensitivity, specificity, PPV, NPV AUC of 98.1%, 95.7%, 94.5%, 98.5%, and 0.969, respectively. Using 2018 ICM the POC test demonstrated a sensitivity, specificity, PPV, NPV and (AUC) of 98.2%, 98.5%, 98.2%, 98.5%, and 0.984, respectively. Using the 2019 proposed EBJIS criteria the POC test demonstrated a sensitivity, specificity, PPV, NPV and area under the curve (AUC) of 93.2%, 100.0%, 100.0%, 94.2%, and 0.966, respectively. Conclusions. The calprotectin lateral flow POC test has an excellent sensitivity and specificity regardless of the set of criteria used to define PJI. These results are promising and suggest that the calprotectin lateral flow test may be used as a rule out test in a cost-conscious health care model or when conventional diagnostic tools may not be available. Further investigations of the calprotectin PCO test must be completed to validate these results

Aims. The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition. Methods. This paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance. Results. This process evolved a three-level approach to the diagnostic continuum, resulting in a definition set and guidance, which has been fully endorsed by EBJIS, MSIS, and ESGIAI. Conclusion. The definition presents a novel three-level approach to diagnosis, based on the most robust evidence, which will be useful to clinicians in daily practice. Cite this article: Bone Joint J 2021;103-B(1):18–25

Aim. Although established serum inflammatory biomarkers, such as serum C-reactive protein (CRP) and serum white blood cell count (WBC), showed low accuracies in the literature, they are still commonly used in diagnosing periprosthetic joint infections (PJI). For a sufficient preoperative diagnosis novel more accurate serum parameters are needed. The aim of our study was to evaluate the performances of the established and novel routinely available serum parameters in diagnosing periprosthetic joint infections when using the proposed European Bone and Joint Infection Society (pEBJIS) criteria. Method. In this retrospective study, 177 patients with an indicated revision surgery after a total joint replacement were included from 2015 to 2019. The easily accessible and routinely available serum parameters CRP, WBC, the percentage of neutrophils (%N), the neutrophils to lymphocytes ratio (NLR), fibrinogen and the platelet count to mean platelet volume ratio (PC/mPV) were evaluated preoperatively. The performances were examined via receiver operating characteristic (ROC) curve analysis (AUC). The curves were compared using the z-test. Seventy-five cases (42%) showed a PJI based on the pEBJIS-criteria. Results. The sensitivities of serum CRP (cut-off: ≥10mg/L), WBC (≥10×10^9 cells/L), %N (≥69.3%), NLR(≥ 3.82), fibrinogen (≥ 457 mg/dL), and PC/mPV (≥ 29.4) were calculated with 68% (95% CI: 57–78), 36% (26 – 47), 66% (54 – 76), 63% (51 – 73), 69% (57 – 78), and 43% (32 – 54), respectively. Specificities were 87% (79 – 93), 89% (81 – 94), 67% (57 76), 73% (63 – 81), 89% (80 – 93), and 81% (72 – 88), respectively. Serum CRP and fibrinogen showed better performances than the other evaluated serum parameters (p<0.0001). The median serum CRP (17.6 mg/L) in patients with PJI caused by a low virulence microorganism was lower compared with infections caused by high virulence organisms (49.2 mg/L; p=0.044). Synovial fluid leucocyte count and histology showed better accuracies than serum CRP, serum WBC, %N, NLR, serum fibrinogen, and PC/mPV (p<0.0001). Conclusions. Although serum CRP and fibrinogen showed the best performances among the evaluated serum inflammatory markers, their results should be interpreted with caution in clinical practice. Serum parameters may remain normal in chronic infections or may be elevated in patients with other inflammatory conditions. In addition, they also correlated poorly with synovial fluid leukocyte count and histology. Therefore, serum parameters are still insufficient to confirm or exclude a periprosthetic joint infection. Hence, they can only be recommended as suggestive criteria in diagnosing PJI

Aim. This study assesses the ability of the JS-BACH classification of bone infection to predict clinical and patient-reported outcomes in prosthetic joint infection (PJI). Method. Patients who received surgery for suspected PJI at two specialist bone infection centres within the UK between 2010 and 2015 were classified using the JS-BACH classification into either ‘uncomplicated’, ‘complex’ or ‘limited options’. All patients were classified by two clinicians blinded to outcome, with any discrepancies adjudicated by a third reviewer. At the most recent follow-up, patients were assessed for (i) any episode of recurrence since the index operation and (ii) the status of the joint. A Cox proportional-hazard model assessed significant predictors of recurrence following the index procedure. Patient-reported outcomes included the EuroQol EQ-5D-3L index score and the EQ-visual analogue score (VAS) at 0, 14, 42, 120 and 365 days following the index operation. Results. 220 patients met the inclusion criteria during the study period which included PJI of the knee (n=111), hip (n=102), shoulder (n=4) and elbow (n=3). The median time to final follow-up was 4.7 years (inter-quartile range 2.7 – 6.7 years). Controlling for type of index procedure and site of infection, Cox proportional-hazards ratio of recurrence when being classified as complex versus uncomplicated was 25.2 (95% CI 3.45 – 183.7, p<0.001) and having limited options verses uncomplicated was 59.0 (95% CI 7.93 – 439.1, p<0.001). None of the patients who were classified as ‘uncomplicated’ PJI (0/52) had received either amputation, joint fusion, excision arthroplasty, chronic suppressive anti-biotics, had died from sepsis secondary to PJI or were awaiting treatment for an active infection at final follow-up. This compared to 21.3% (27/127) of patients classified as ‘complex’ PJI and 65.9% (27/41) of patients classified as ‘limited options’. Compared to the age-matched population, patients with ‘uncomplicated’ PJI reported similar EQ-index scores (age-matched population: 0.782, ‘uncomplicated’: 0.730, SD 0.326) and EQ-VAS (age-matched: 77.9, ‘uncomplicated’ PJI: 79.4, SD 20.9). This was significantly higher when compared to patients classified as ‘complex’ (EQ-index: 0.515 SD 0.323, p<0.012; EQ-VAS: 68.4 SD 19.4, p=0.042) and ‘limited options’ (EQ-index: 0.333 SD 0.383, p<0.001; EQ-VAS: 60.2, SD 23.1, p=0.005, ANOVA with Tukey post-hoc comparison). Conclusions. We have demonstrated that the JS-BACH classification for bone and joint infection is a significant predictor of clinical outcome and quality of life following surgery for PJI. This will allow clinicians to offer prognostic information to patients and guide the timing of referral for specialist management in PJI

Aim. Many bone and joint infections, in spite of appropriated antibiotics therapy and surgery, lead to a therapeutic dead end. We are then faced with a chronic infection with or without continuous antibiotic treatment, with daily local care, and an exhorbitant economic and social cost. Pami the incriminated factors: the presence of foreign implant material, the poor diffusion of antibiotics at the infectious site, the presence of biofilm. The bacteriophages, biological drug, natural environmental viruses possess the properties to meet these difficulties: well diffusion to the infectious focus with possibilities of local use, destruction of the biofilm allowing a release of the bacteria and a synergistic effect with the antibiotics, antibiofilm effect for the restoration of osteoblastosis. Method and results. We report a cohort of phage - treated patients with or without antibiotics in bone and joint infections in a therapeutic dead end. Without disponibility of therapeutic phages available in the European Union, commercial cocktails of phages, antistaphylococcal or polyvalent, of Russian* or Georgian** origin were used. Ten patients have benefited since 2008 from phages, alone or in combination with an adapted antibiotic therapy. Patients were 40 to 89 years old and had chronic bone and joint infections except for one case with acute MRSA infection on femoral implant. Bacteria were Staphylococcus aureus 7 times, Pseudomonas aeruginosa 3 times, Klebsiella 2 times. In 4 cases implant was left in place (knee prosthesis, femoral screw plate) or introduced (1 screw in 1 case) during the procedure. In all cases except 1 patient, the phages were applied in per-operative. With a follow-up of up to 9 years for some patients, the initial bacteria were eradicated and in 2 cases replaced by another bacterium (Pseudomonas in place of S. aureus in one case and Enterococcus in place of P. aeruginosa for an elderly patient with a knee prosthesis without possible surgery. Conclusion. The combination of surgery, phages and antibiotics appear a very efficient option, to treat patients with bone and joint infections in therapeutic dead end. The quick availability of these treatments for these patients is a health emergency. *Microgen® Pharma. **Eliava Institute

Aim. Management of bone and joint infection can be technically complex and often requires a prolonged course of antibiotics. Traditionally, bone and joint infection management utilises nurse-led outpatient parenteral antibiotic therapy (OPAT) where adherence is unlikely to be an issue. However, with increasing evidence in favour of oral therapy, the question of adherence merits further consideration. We describe the adherence of both oral (PO) and self-administered intravenous (IV) antibiotics in the treatment of bone and joint infection using paper questionnaires (8-item Modified Morisky Adherence Score (MMAS)) and, in a subset of participants, electronic pill containers (Medication Event Monitoring Systems*). Method. All eligible participants enrolled in the OVIVA trial (2010–2015) were randomised to six weeks of either PO or IV antibiotic treatment arms. Self-administering patients were followed up with questionnaires at day 14 and 42. A subset of PO participants was also given the medication event monitoring system* in order to validate the adherence questionnaires. The results were correlated with treatment failures at one-year follow-up. Results. 1,054 participants were enrolled in the OVIVA study. At day 14, 68% of participants recorded high adherence in both the IV (N=72) and PO arms (N=303) using the 8-item MMAS. At day 42, only 51% maintained high adherence in the PO arm (N=323) as compared to a 68% in the self-administered IV arm (N=80). The medication event monitoring system* results at day 42 demonstrated that 51% of participants achieved adherence of 100% (range 45–100). There was no statistically significant correlation between adherence and treatment failure in either randomised treatment arm. Conclusions. This is the first large scale study to quantitatively assess compliance with antibiotics in bone and joint infections using established adherence tools. Our results suggest that oral antibiotic adherence decreases significantly over time. Despite the absence of apparent excess risk of therapeutic failure in this trial, we strongly advise careful patient education and adherence support in order to optimise clinical outcomes. Acknowledgements. The OVIVA study is funded by the National Institute for Health research (Health Technology Assessment); project number 11/36/29. *MEMS® Medication Event Monitoring System

Aim. Bone and joint infections are a serious complication of trauma, surgery and soft tissue infections. However, there are few data presenting patient reported outcome measures for osteomyelitis. A recently proposed method for classification of osteomyelitis, BACH, stratifies patients into ‘uncomplicated’ and ‘complex’, based on four key inter-disciplinary components: . B. one involvement, . A. nti-microbial options, soft-tissue . C. overage and . H. ost status. We aim to correlate the classification severity with patient reported outcomes following osteomyelitis surgery. Method. Seventy-one patients with long-bone osteomyelitis, confirmed using a validated composite protocol, were included. Patients received a single-stage procedure at a specialist bone infection unit. Euro-Qol EQ-5D-3L questionnaires and Visual Analogue Scores (VAS) (0–100) were collected prospectively at baseline, 14 days, 6 weeks, 4 months and 1 year post-operatively. The EQ-5D-3L index score, a composite measure of performance of daily activities, was calculated from the 5 domains of the EQ-5D-3L. BACH was applied retrospectively by two independent clinicians blinded to all patient outcomes. Results. There was significant improvement in VAS (58.2 vs. 78.9, p<0.01) and EQ-5D-3L index (0.284 vs. 0.740, p<0.01) scores from baseline to 1 year. ‘Uncomplicated’ osteomyelitis was associated with significantly higher EQ-5D-3L and VAS at 1 year follow-up when compared to ‘complex’ osteomyelitis (EQ-5D-3L: 0.900 vs. 0.685, p<0.01; VAS: 87.1 vs. 73.6, p<0.05). Patients with cavitary bone involvement (BACH type B1) reported higher outcome scores at all time points when compared to segmental involvement (B2) or infection involving the joint (B3). Good antimicrobial options gave higher outcome scores compared to patients with multi-drug resistant isolates (A2). Patients who had received microvascular tissue transfer (C2) initially reported lower outcome measures but returned to a similar level to patients who had their wounds closed directly (C1) from 6 weeks. Patients with severe co-morbidity (H2) reported lower outcome scores at all time points compared to those who were fit or with well controlled disease (H1). Conclusions. Complex cases of osteomyelitis as defined by BACH classification, had poorer patient reported outcomes compared to uncomplicated cases. This was despite being managed in a centre that specialises in bone and joint infection. This study demonstrates that BACH is helpful for assessing case complexity and prognosis in osteomyelitis

Culture examination is still considered the gold standard for diagnosis of bone and joint infections, including prosthetic ones, even if in up to 20–30% of cases, particularly prosthetic joint infections, it fails to yield microbial growth. To overcome this limitation, determination of markers of inflammation and or infection directly in joint fluid has been proposed. Aim of this study was to evaluate the applicability of measurement of lecukocyte esterase (LE), C-reactive protein (CRP) and glucose in synovial fluid for diagnosis of bone and joint infections. Synovial fluids from 80 patients were aseptically collected and sent to laboratory for microbiological cultures. After centrifugation at 3000 rpm for 10 minutes, pellet was used for cultures, while the surnatant was used for determination of LE, CRP and glucose. LE and glucose were evaluated by means of enzymatic colorimetric strips developed for urinanalysis. One drop of synovial fluid was placed on the LE and on the glucose pads and the results were read after about 120 seconds. A LE test graded + or ++, and a glucose test equal to trace or negative were considered suggestive for infection. CRP was measured by an automated turbidimetric method. On the basis of clinical findings, microbiological, haematological and histological analyses patients were retrospectively divided into 2 groups. Group 1 comprised 19 infected patients (12 males, 7 females age: 70.6 ± 10.3 yrs, range: 47 – 88 yrs) while Group 2 included 61 aseptic patients (32 males and 29 females, age: 61.5 ± 16.3 yrs, range: 15 – 84). Sensitivity of the three tests was 89.5%. 84% and 73,7% for LE, CRP and glucose, respectively. Specificity was 98.4%, 88.5% and 70% for LE, CRP and glucose, respectively. Positive and negative predictive values were 94.4% and 96.8% for LE, 69.6% and 94.6% for CRP and 77.8% and 89.6% for glucose test. When LE was combined with CRP, sensitivity increased to 94.7%, while no differences were observed for LE combined with glucose. Leukocyte esterase has proven to be a rapid, simple and inexpensive test to rule in or out bone and joint infections. Combination of its measurement with that of CRP increased sensitivity. In conclusion, the combination of leukocyte esterase and CRP may represent a simple and useful tool for diagnosis of bone and joint infections

Purpose of the study: Infection is a leading cause of morbidity and mortality in sickle cell anemia children. It often triggers an acute episode of anemia with thrombosis. Bone and joint infections are particularly frequent. Diagnosis can be difficult and is sometimes established late. Material and methods: We analyzed retrospectively the cases of 39 children with sickle cell anemia who presented one or more bone and joint infections during a six-year period (January 1998-December 2003). Results: Bone and joint infection involved 14% of all sickle cell children hospitalized during the study period. Mean age was nine years, with no gender predominance. Homozygous subjects were more exposed to infection (73%). The infection revealed the disease in 13% of the children. The rate of bone and joint infection was 62% compared with 38% for osteomyelitis; salmonella were isolated in 38% of cases. Medical treatment with adapted antibiotics and plaster cast immobilization were instituted in all cases and associated with surgical treatment in 25% (arthrotomy for evacuation of purulent collections, cleaning, resection of infected tissue). Outcome was favorable in 77% of cases (cured infection, resumed school activities). Discussion: The frequency of bone and joint infections in sickle cell anemia children in our series was similar to that reported in the literature (10–19%). Compared with children with normal hemoglobin, bone and joint infection in sickle cell anemia children present specific features in terms of localization, blood chemistry findings, causal bacteria, radiographic signs, and therapeutic modalities and sequelae. Conclusion: Sickle cell anemia is a serious hereditary disease. The risk of complications should lead to the development of preventive measures (screening at risk couples, institution of a prenuptial certificate, allogenic bone marrow graft)

Aim. To evaluate the analytical performance of synovial fluid D-lactate test for the diagnosis of PJI. Method. Consecutive patients undergoing diagnostic joint aspiration of prosthetic joint were prospectively included. PJI was diagnosed according to the proposed European Bone and Joint Infection Society (EBJIS) definition criteria. Synovial fluid was collected for culture, D-lactate measurement (by spectrophotometry, λ = 570 nm) and leukocyte count and differential (by flow cytometry). The receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of D-lactate and leukocyte count. Results. Diagnostic joint aspiration was performed in 224 patients with prosthetic joints. PJI was diagnosed in 87 patients (39%). The optimal D-lactate cut-off value for diagnosing PJI was 1.2 mmol/l. The sensitivity of synovial fluid D-lactate was 97.7%, specificity 83.9%, whereas the sensitivity of synovial fluid leukocyte count was 87.5% with specificity 95.7%. Concentration of SF D-lactate was significantly higher in patients with PJI compared to aseptic loosening of prosthesis (median (range)) 2.33 (0.99–3.36) vs 0.77 (0.01–2.4), p<0.0001. We found positive correlation between D-lactate and erythrocytes in synovial fluid sample in the aseptic group (ρ = 0.339, p< 0.01). Conclusions. The synovial fluid D-lactate showed a good diagnostic performance for the diagnosis of PJI, which was comparable to the synovial fluid leukocyte count. Currently available (UV)-based method for detection of D-lactate showed low specificity (84%) due to influence of hemoglobin with the similar absorbance wavelengths (λ = 540 nm). More specific high-performance methods such as electro-chemical sensing system or lateral flow immunochromatographic assays should be implemented

Aim. Our hospital is a referral center for Bone and Joint Infection (BJI) with a 15-bed orthopedic unit. Patients benefit from a multidisciplinary team management (surgeons, anesthetists, infectious disease physicians, microbiologists, dietician etc.). Computerized drug prescriptions are performed by anesthetists, surgical residents, surgeons and infectious disease physicians. Since 2015, a pharmacist has been included in ward rounds and in weekly multidisciplinary consultative meetings, where antibiotic treatment strategies are decided for hospitalized patients. This work aimed to assess the impact of a pharmacist in this unit to limit prescription errors. Method. Prospective monocentric study of all pharmacist's advice or interventions during 15 weeks in 2016 and 2017. A complete pharmaceutical analysis of prescriptions is performed twice a week at least. This analysis is based on doses control and drug interactions, but also takes into account biological and clinical data of patients (patient history, renal function, symptoms, adverse effects…). In case of a prescription error, a computerized message and/or a phone call is sent to the prescriber. Each pharmacist's intervention is recorded and classified according to the French Society of Clinical Pharmacy. The pharmacist collected the number of pharmaceutical advice (when spontaneously solicited by any member of the multidisciplinary team), the different types of prescription errors, the pharmacological class associated to these errors, the types of pharmacist's interventions and their impact on prescriptions. Results. During ward rounds, 24 pharmaceutical advices were asked spontaneously by physicians about drug treatment optimization, predominantly about preparation and administration of injectable antibiotics or about doses adaptation. Regarding medication problems detected by the pharmacist, there were 145 prescription errors: inappropriate dose (38/145), too long-duration treatment (24/145), drug omission (18/145), drug overlap (13/145), inappropriate route (13/145), drug interaction (10/145), non-adherence to guidelines (15/145), omission of specific monitoring (4/145), other (10/145). The main pharmacist's interventions were drug discontinuations (53/145, 37%) and dose adjustments (37/145, 26%). In this specific BJI unit, 67/145 (46%) pharmacist's interventions were related to antibiotic drugs, 29/145 (20%) to drugs for digestive disorders and 16/145 (11%) to cardiovascular drugs. Most of pharmacist's interventions were accepted by prescribers (123/145, 85%), with immediate correction of prescriptions. Conclusions. Most prescription errors concerned doses and durations of treatments. Antibiotic prescriptions were often susceptible to errors. The involvement of a pharmacist in this bone and joint infection unit allows a better medication safety

Aim. The risk of haematogenic periprosthetic joint infection (PJI) after dental procedures is discussed controversially. To our knowledge, no study has evaluated infections according to the origin of infection based on the natural habitat of the bacteria. We investigated the frequency of positive monomicrobial cultures involving bacteria from oral cavity in patients with suspected PJI compared to bone and joint infections without joint prosthesis. Method. In this retrospective study we included all patients with suspected PJI or bone and joint infection without endoprosthesis, hospitalized at our orthopaedic clinic from January 2009 through March 2014. Excluded were patients with superficial surgical site infections or missing data. Demographic, clinical and microbiological data were collected using a standardized case report form. Groups were compared regarding infections caused by oral bacteria. χ2 test or Fisher's exact test was employed for categorical variables and t-test for continuous variables. Results. A total of 1673 patients were included, of whom 996 (60%) had a suspected PJI and 677 (40%) an osteoarticular infection without joint endoprosthesis (control group). In patients with suspected PJI the median age (standard deviation) was 67 (14) years; 407 (41%) were males. The anatomic location of the prosthesis was hip in 522 (52%) patients, knee in 437 (44%), megaprostheses in 14 (1%), shoulder in 8 (1%) and other endoprosthesis in 15 (2%) patients. In 437 (44%) of PJI cases pathogen(s) were detected, 271 (62%) were monomicrobial and 166 (38%) polymicrobial. Of 996 patients with suspected PJI, 2.4% (n = 24) had monomicrobial infections caused by bacteria belonging to the normal oral flora, predominantly oral streptococci (n = 21). In contrast, only 0.4% (n =3) of the control group without joint prosthesis had monomicrobial infections caused by oral bacteria. This difference was statistically significant (p = 0.002), whereas the patient age (p = 0.058) and the anatomic location of the joint prosthesis (p = 0.622) did not have any effect on the infections due to oral bacteria. Conclusions. The incidence of infections caused by oral bacteria was significantly higher in patients with endoprosthesis than in other osteoarticular infections (2.4% versus 0.4%). This finding indicates that joint prostheses are at risk of haematogenous PJI originating from oral cavity. Future prospective studies need to determine the exact risk of haematogenic PJI caused by oral bacteria, as well as the potential of preventing these infections by antibiotic prophylaxis

Aim. Treatment of chronic prosthetic joint infection (PJI) combines exchange arthroplasty and effective antibiotic therapy. Staphylococci are the most frequent microorganism isolated in PJIs, with resistance to methicillin found in 15–50% of the cases. Data from randomized trials on treatment of methicillin-resistant staphylococci are lacking and the choice of antibiotic(s) and recommendations vary according to authors. To date, combination therapy including vancomycin is the treatment of choice. Minocycline, a cyclin antibiotic, is naturally effective against methicillin-resistant staphylococci. We use this antibiotic since many years in combination with vancomycin for the treatment of multi-drug resistant staphylococcal bone and joint infections. The aim of this study is to analyze the outcome of patients treated with combination antibiotic therapy including minocycline for the treatment of chronic methicillin-resistant staphylococcal PJI. Method. We conducted a cohort study between 2004 and 2014 in our referral center for bone and joint infections. Data were extracted from the prospective database. All the patients receiving an initial combination therapy including at least 4 weeks of minocycline, given orally, and another IV antibiotic, usually high-dose continuous IV vancomycin, for chronic MR staphylococcal PJI and who underwent one or two stage exchange arthroplasty, were included. They were followed prospectively for at least 2 years. Results. We included 42 patients: 26 patients (62%) had one-stage, 16 patients (38%) had two stage exchange arthroplasty. Median duration of IV and total antibiotic therapy was 42 [40–44] days and 84 [84–88] days, respectively. 41 patients (98%) received vancomycin as associated initial therapy. Thirty-six patients received 100mgx3 per day of minocycline. Six received >300mg per day because of low serum concentrations. Median follow-up was 48 months (IQR 27–58). Survival rate without infection was 84,5% at 2 years, 70.2% at 6 years. Four patients reported adverse events due to minocycline: one had grade 4 thrombopenia leading to minocycline withdrawal, two had grade 2 liver toxicity. One patient had grade 1 nauseas. Two patients with MR Staphylococcus epidermidis knee arthroplasty experienced relapse. Three patients with hip arthroplasty infection developed a new infection within 2 year due to MSSA, Pseudomonas aeruginosa, and plurimicrobial for the last one. Three further patients developed a new infection 3 (n=2) and 4 years later. They were all acute haematogenous infections. Conclusions. Our data support the use of minocycline combination therapy with high-dose IV vancomycin for the treatment of chronic PJI due to methicillin-resistant Staphylococci

Aim. Bone and joint infections are frequent in African countries and their prevention and treatment remain a great challenge. This study aimed to determine the bacterial ecology and sensitivity of isolates to locally available antibiotics in orthopedic unit of a tertiary care hospital in Cameroun. Method. During a 12 months period, all the patients presenting with osteomyelitis or septic arthritis irrespective of the mechanism and the location were enrolled in this study. Intraoperative samples (biopsies) were taken and sent for microbiological analysis, and all strains isolated were tested for antibiotic sensitivity according to conventional methods. Results. on the 52 bacteriological analysis performed, 48 were positive. The most isolated germs were staphylococcus aureus (41.9 % of isolates), pseudomonas aeruginosa (14.5 %), Escherichia coli (14.5 %) and Klebsiella pneumonia (12.9 %). The antibiotic sensitivity pattern revealed worrying resistance rates for common and affordable antibiotics: ampicillin (94 %), amoxicillin + clavulanic acid (63.9 %), ceftazidim (65.5%), ticarcillin + clavulanate (57.4%), gentamycin (49 %), ciprofloxacin (40 %), cefuroxim (40 %), tobramycin (38.5 %). The strains of Staphylococcus aureus showed resistance to penicillin G (83%), oxacillin (25%), lincomycin (27%) and vancomycin (7%). The overall highest sensitivity rates were observed with amikacin (92 %) and imipenem (90.1%), which for many patients were the only effective locally available antibiotics. The daily cost of treatment with those two antibiotics is close to the guaranteed minimum wage in our country. Conclusions. The alarming rate of multidrug-resistant bacteria makes the long antibiotic treatment of bone infections unaffordable (in a context of lack of social insurance) for most of our patients. We advocate strong national policies for bacteriological surveillance and antibiotic misuse de-escalation to prevent antibiotic resistance

Aims

The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol.

Aim. To assess the role of Tc-99m labelled anti granulocyte monoclonal antibody Fab' fragment (Sulesomab) in the diagnosis of bone and joint infections. Methods. We analysed the results of 95 patients referred with a clinical suspicion of bone and joint infections. There were 47 male and 48 female patients with a mean age of 60 years (range=16 to 89). Referrals were made for suspected infection of prosthetic total joint replacements (38), long bones (32), primary joints (12) and feet (13). Sulesomab imaging was done with 650 MBq of 99mTcSulesomab. The final diagnosis was determined by conclusive microbiology, culture and/or histology, intra-operative findings, aspiration, complementary investigations like CT/MRI and long term clinical follow-up. The findings of 99mTcSulesomab images were compared with the clinical outcome to arrive at the decision of True Positive/ False positive/ True negative/ False negative results. Using the above definitions sensitivity, specificity and diagnostic accuracy of 99mTcSulesomab for suspected bone and joint infection were calculated. Results. 58/95 patients had normal or equivocal blood results. Plain radiographs revealed no abnormality or were inconclusive of infection in more than half of the patients. Outcome classification revealed 29 true positives, 56 true negatives, 9 false positives and one false negative. The overall sensitivity was 96.66% and specificity 86.15% with a negative predictive value of 98.24%. The individual sensitivity and specificity of each category was compared. Diagnostic accuracy for long bone infections (96.87%) was the highest than any other group. Conclusion. 99mTc Sulesomab imaging has a high sensitivity and specificity in a heterogeneous group of orthopaedic bone and joint infections. With a high negative predictive value, this test seems to be useful in excluding orthopaedic infection rather than confirming it

Aim. Apart from other biomarkers isolated in the synovial fluid, alpha-defensin appears to be a promising diagnostic tool to confirm a periprosthetic joint infection (PJI) in the hip or knee. The purpose of this study was to evaluate the sensitivity and specificity of an alpha defensin lateral flow (ADLF) test compared to usual standard classifications in the diagnostic management of PJI. Method. This investigation was set up as a multicenter prospective cohort study. Synovial fluid was obtained by means of joint aspiration or intra-operative tissue biopsies. A presumptive PJI diagnosis was made according to criteria outlined by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA) and the European Bone and Joint Infection Society (EBJIS). The intention to treat by the surgeon was logged. Sensibility and specificity for the ADLF test was plotted for each aforementioned diagnostic algorithm. Spearman correlations between all scores were analyzed. Multiple logistic regression was used to determine the contribution of independent variables to the probability of PJI. Results. Hundred thirty-six patients with a painful arthroplasty were assessed for infection and rated by the treating surgeon as potentially infected or not on the basis of clinical and laboratory information. According to the EBJIS criteria sixty-eight patients were deemed infected, fifty according to the IDSA criteria, forty-one according to the MSIS criteria and forty according to the ADLF test. However, the sensitivity of ADLF test was 87.8% for MSIS, 70% for IDSA and 55.8% for EBJIS. The specificity of ADLF test was between 94% – 97%. Good correlation was observed between synovial fluid culture and ADLF test (r = 0.73). Low to excellent correlations between the ADLF test and the EBJIS (r = 0.58), IDSA (r = 0.68), and MSIS score (r = 0.84) were observed. The surgeon's intention to treat correlated well with the MSIS score (r = 0.86), and moderately with the EBJIS (r = 0.59). Conclusions. ADLF test sensibility was variable, but its specificity was excellent. Most of the cases, not retained by MSIS but classified by EBJIS as infected, got a negative microbiological result. Considering an accepted 20% negative microbiological result rate in PJI diagnostic, EBJIS is clearly overestimating the number of infected cases. MSIS score correlates with the surgeon intention to treat and ADLF test

Aim. Cutibacterium acnes (CA) is one of the crucial actors in spine instrumentation or shoulder prosthesis. Its population is subdivided into 6 major phylotypes: IA1, IA2, IB, IC, II and III. Recent methods for discriminating subpopulations within CA phylotypes highlight the predominance of SLST types H1 to 6 or K1 to 20 in bone and joint infection (BJI). The impact of their ability to produce a biofilm during the development of the infection (with resistance / tolerance to antibiotics used for treatment) remains little studied. Method. The purpose of this study was to determine whether the ability to establish a biofilm varied according to the different subtypes of clinical strains of CA previously characterized and involved in BJI (hip, knee and shoulder prosthesis). The BioFilm ring test (BioFilm Control®) method with index determination, called BFI (BioFilm Index) inversely proportional to the level of biofilm production was used (BFI = 0.00 indicates a high production of biofilm versus BFI = 20.00 indicates zero production). The BFI was determined after 3 h (T3) and 6 h (T6) incubation. The strains used came from patients, 5 belonging to the IA1 phylotype (SLST A1 and D1 types) and 4 to different phylotypes (IA2, IB, II and III). Results. The results show that the kinetics of establishment of an early CA biofilm turns out to be phylotype dependent. The most productive strains are those belonging to phylotype II (BFI T3 = 5.73, BFI T6 = 0.00) and to type SLST D1 belonging to phylotype IA1 (BFI T3 = 4.07, BFI T6 = 0.00). The other strains did not demonstrate saturated BFI, even after 6 h of incubation. Conclusions. The exact role of CA, as well as its ability to produce a biofilm in the pathophysiology of BJI, remains poorly understood and the prolonged use of antibiotics to treat these infections is necessary, especially if devices have not been removed, with potential risk of increasing antibiotic resistance and therapeutic failures. CA's different phylotypes demonstrate different biofilm production capabilities, which could have an impact on the antibiotic efficacy suggesting the interest of effective anti-biofilm molecules on metabolically less active strains

Aim. Staphylococcus aureus is the first causative agent of bone and joints infections (BJI). It causes difficult-to-treat infections because of its ability to form biofilms, and to be internalized and persist inside osteoblastic cells. Recently, phage therapy has emerged as a promising therapy to improve the management of chronic BJI. In the present study, we evaluated the efficacy of an assembly of three bacteriophages previously used in a clinical case report (Ferry, 2018) against S. aureus in in vitro models of biofilm and intracellular osteoblast infection. Methods. Using HG001 S. aureus, the bactericidal activities of the assembly of the three bacteriophages (Pherecydes Pharma) used alone or in association with vancomycin or rifampicin were compared by quantifying the number of viable bacteria in mature biofilms and infected osteoblasts after 24h of exposure. Results. The activity of bacteriophages against biofilm-embedded S. aureus was dose-dependent. Synergistic effects were observed when bacteriophages were combined to antibiotics at the lowest concentrations, with no significant bactericidal activity in monotherapy. In the human osteoblast infection model, we were able to show that phage penetration into osteoblasts was only possible when the cells were infected, suggesting a S. aureus dependent Trojan horse mechanism. The intracellular inoculum in osteoblasts treated with bacteriophages or vancomycin was significantly higher than in cells treated with lysostaphin, used as control condition of rapid killing of bacteria released in the extracellular media after death of infected cells and absence of intracellular activity. These results suggest that bacteriophages are probably both i) inactive in the intracellular compartment and ii) unable to kill all bacteria released after cell lysis into the extracellular medium fast enough to prevent them from reinfecting other osteoblasts. Conversely, the intracellular inoculum recovered from cells treated with vancomycin+bacteriophages was significantly lower than the one inside cells treated with vancomycin or bacteriophages alone, suggesting that this combination allowed a better control of released bacteria in the extracellular media. Finally, bacteriophages did not increase the activity of rifampicin in this model. Conclusion. In conclusion, we showed that the bacteriophages tested were highly active against S. aureus in mature biofilm but had no activity against bacteria internalized in osteoblasts. Additional studies using animal models of BJI and well-conducted clinical trials are needed to further evaluate phage therapy and its positioning in the management of these infections

Aims

To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

Aims

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO₄) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO₄ applied locally to treat ODAI.

Aims

Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella.

Aim. We evaluated the efficacy and safety of treatment regimens in a pathogen and surgery specific mode according to a standardized algorithm for the treatment of periprosthetic joint infection (PJI) based on combinations with 15g/d intravenous fosfomycin followed by oral antibiotics for totally 12 weeks. Method. Consecutive patients with PJI caused by at least one of the following isolates were prospectively included: staphylococci (MIC ≤32 mg/l), streptococci (MIC ≤128 mg/l), enterococci (MIC ≤128 mg/l), Enterobacteriaceae (MIC ≤32 mg/l) and Pseudomonas spp. (MIC ≤128 mg/l). PJI was defined by the proposed European Bone and Joint Infection Society (EBJIS) criteria. Follow up with clinical (joint function and quality of life scores), laboratory and radiological evaluation at 3, 12 and 24 months after last surgery is performed. Infection outcome was assessed as the proportion of infection-free patients. The probability of infection-free survival was estimated using the Kaplan-Meier survival method. Results. 50 patients were screened for eligibility, of which 2 were excluded due to intolerance or allergy to fosfomycin, 1 due to isolation of fosfomycin resistant pathogen and 2 patients died due to unrelated cause to infection. The remaining 45 patients were included. Due to persistence of infection, 3 patients underwent prosthesis explantation after initial debridement and retention, 1 patient underwent debridement of Girdlestone-situation; all 4 infections were caused by S. aureus. At 2 patients debridement of hematoma after Girdlestone approach was performed. 41 patients were infection-free (91%) after a median follow-up of 6 month (range, 1 – 14 months). Nausea (n=14) and hypokalemia (n=13) were the most frequent adverse events and resolved after fosfomycin discontinuation; 5 patients had diarrhea and vomiting was observed in 2 patients. Isolated pathogens were staphylococci (n=30), streptococci (n=3), enterococci (n=5) and gram-negative rods (n=2). Cultures were negative in 9 patients and polymicrobial in 2 patients. The infection occurred postoperatively in 31 patients (69%) and hematogenously in 14 (31%). Two-stage exchange was performed in 27 (60%), debridement with retention in 13 (29%) and one-stage exchange in 5 patients (11%). Conclusions. The applied PJI treatment algorithm including intravenous fosfomycin in the initial postoperative period was associated with infection-free outcome of 91% after a median follow-up of 6 month. The Kaplan-Meier survival method showed the probability of infection-free survival of 88.5% after 1 year. Adverse events occurred in 21 patients (46%) mostly nausea and hypokalemia were reported. Adverse events were mild and resolved completely

Introduction. Polymicrobial infections are expected to complicate the treatment of bone and joint infections. Septic nonunions often occur after initial open fractures, which prophylactically receive broad-spectrum antibiotics. However, no data that describes frequencies of polymicrobial infections and pathogens evident in course of the treatment of septic nonunions is published. Therefore, this study aims at investigating the frequency and pathogen types in polymicrobial infections. Methods. Surgically treated Patients with long bone septic nonunion admitted between January 2010 and March 2018 were included in the study. Following parameters were examined: age, gender, American Society of Anesthesiologists (ASA) score, body mass index (BMI), and anatomical location of the infected nonunion. Microbiological culture data, polymerase-chain-reaction results of tissue samples, sonication, and joint fluid of the initial and follow-up revision surgeries were assessed. No exclusion criteria were determined. Results. The study encompassed 42 patients with a mean age of 53.9 ± 17.7 years (range, 23 – 93). Sixteen (38.1%) patients were female. In 46.3% of the patients open fractures led to septic nonunion. Twenty-six nonunions occurred at the tibia or fibula, 11 were localized at the femur, 2 at the humerus and 3 at the forearm. Only 2 patients were assessed as ASA type 1, while 26 were ASA type 2 and 12 patients ASA type 3. Mean number of performed surgeries was 6 ± 0.67 (range 2 – 21). In 6 patients (14.3%) polymicrobial infection were evident. A change of evidenced pathogens in course of the treatment occurred in 21 patients (50%). In 16 patients (38.1%) previously detected bacteria could be evidenced by microbial testing after further revision surgery. Staphylococcus aureus was most often evident (n=34, 30.6%), followed by Enterococcus species (n=25, 22.5%) and Staphylococcus epidermidis (n=18, 16.2%). Five Staphylococcus aureus were resistant to methicillin (MRSA). In patients without polymicrobial infection or further germ detection in course of the treatment 86.4% of the infections were due to Staphylococcus species. Patients with change of detected pathogens and polymicrobial infections suffered from more enterococci infections. Infections due to streptococci and gram-negative bacteria could only be evidenced in patients with polymicrobial infection and pathogen change in course of the treatment. Conclusion. The observed difference of microbiological patterns in septic nonunion may help to facilitate adjuvant local and systemic antibiotic treatment in septic nonunion patients. Reasons for the observed difference of microbiological patterns and its influence on patient outcome have still to be elucidated

Background. Preoperative diagnosis of fracture related infections can be challenging, especially when confirmatory criteria such as sinus tract and purulent discharge are absent. Although serum parameters, such as CRP and white blood cell count (WBC), showed poor accuracy in the literature, they are still often used in clinical practice. The European Bone and Joint Infection Society (EBJIS) defined evidence-based criteria for fracture related infection. Elevated serum inflammatory markers were regarded as suggestive criteria only, as the literature was of limited quality. This study assessed the diagnostic value of the serum parameters CRP, WBC and differential cell count in the diagnosis of fracture related infections defined by the EBJIS-criteria for fracture related infections. Methods. In this retrospective cohort study, 94 patients who underwent surgical treatment for suspected infected non unions after failed fracture fixation were included. Preoperatively, blood samples including serum inflammatory markers were taken. For this study, cut-offs of 5 mg/L for CRP, 10×10⁁9 cells/L for WBC, and >70% for the percentage of neutrophils were regarded as positive for infection. All patients had intraoperative samples taken for microbiology and histology. Analysis of diagnostic accuracy was based on the receiver-operating characteristic (ROC). Results. Based on the EBJIS criteria, 40 patients (43%) were diagnosed with a fracture related infection. 11/94 (12%) patients had an elevated serum WBC count, 13/94 (14%) an increased percentage of neutrophils, and 43/82 (52%) an elevated serum CRP. The mean values of CRP concentration, WBC count, and percentage of neutrophils in the infection group were 7.9 mg/L (IQR:6.4 – 9.7), 18.3 G/l (IQR: 3.9 – 24.9), and 63% (IQR: 58 – 67%), respectively. The sensitivity, specificity, and area under the curve of serum WBC count were 20% (95% CI: 10 −35%), 94.4% (84 −99%), and 0.57 (0.50 – 0.64), respectively; of percentage of neutrophils 12.5% (5 – 27%), 85.2% (73 −93%), and 0.49 (0.42 – 0.56); and of serum CRP 67.6% (51 – 90%), 60.0% (45 – 73%), and 0.64 (0.53 – 0.74), respectively. A statistically significant difference between the AUCs of all three serum parameters and AUC of tissue culture as well as AUC of histology was shown (p <0.0001). A simple decision tree approach using only low WBC and CRP may allow identification of aseptic cases. Conclusion. Based on the standardized and evidence-based EBJIS criteria, the three inflammatory serum markers showed an insufficient accuracy for the diagnosis of fracture related infections. They also correlate poorly with culture or histological diagnosis. Therefore, they should not be used alone as a confirmatory test

In 2017, the British Society for Children’s Orthopaedic Surgery engaged the profession and all relevant stakeholders in two formal research prioritization processes. In this editorial, we describe the impact of this prioritization on funding, and how research in children’s orthopaedics, which was until very recently a largely unfunded and under-investigated area, is now flourishing. Establishing research priorities was a crucial step in this process.

Cite this article: Bone Joint J 2024;106-B(5):422–424.

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area.

Cite this article: Bone Joint J 2022;104-B(11):1193–1195.