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

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

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.

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

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