Efficacy and safety of co-trimoxazole in device-related bone and joint infections: a CRIOGO multicentre case-control study.

OBJECTIVES: Co-trimoxazole could be an alternative antibiotic to treat device-related bone and joint infection (BJI) but there are few published data about its efficacy and safety in this complex scenario to treat infection. The objective was to compare the outcome of patients with device-related BJI treated with an antibiotic regimen including co-trimoxazole versus a regimen without co-trimoxazole. METHODS: This multicentre case-control study included consecutive adult patients diagnosed with device-related BJI. Each patient receiving co-trimoxazole was included in the co-trimoxazole group and was matched with two control patients, with stratification on microbial aetiology and age. The primary outcome was composite and defined by death or treatment failure during the follow-up. RESULTS: In this study, 150 patients were included, 50 in the co-trimoxazole group and 100 in the control group. The rate of reaching the primary endpoint was 18% in the co-trimoxazole group (9/50 cases) versus 21% in the control group (21/100) (P = 0.66). Co-trimoxazole use was not associated with an unfavourable outcome in the multivariate analysis (adjusted OR 0.8, 95% CI 0.31-2.06, P = 0.64). Although no significant difference was observed in premature discontinuation of treatment due to an adverse event between both groups (14 versus 12%, P = 0.73), treatment-related adverse events were significantly more frequently reported in patients of the co-trimoxazole group than the control group [34% (17/50) versus 18% (18/100), P = 0.03]. CONCLUSIONS: Co-trimoxazole appears to be an effective alternative for the treatment of BJI, even when it occurs on a device, but the safety profile requires close monitoring of adverse effects.

Management and outcome of native joint septic arthritis: a nationwide survey in French rheumatology departments, 2016-2017.

OBJECTIVES: To describe current management and outcome of native joint septic arthritis (NJSA) in French rheumatology departments. METHODS: For this retrospective, nationwide multicentric study, 127 French rheumatology departments were contacted to report up to 12 cases of NJSA that occurred between 1 January 2016 and 31 December 2017. Characteristics, diagnosis procedures, therapeutic management and outcome were recorded. RESULTS: Overall, 362 patients were included (mean age 64.0±18.6 years, median Charlson comorbidity index 3.5 (0-14)). Knee was the most frequent site (n=160 (38.9%)), and Staphylococcus sp (n=185 (51.4%)), the most frequent pathogen. All patients received antibiotics for a mean duration of 46.8 (±22.0) days, including intravenous route for a mean of 17.2 (±15.4) days. Management was heterogeneous. Surgical procedure was performed in 171 (48.3%), joint immobilisation in 128 (43.8%). During follow-up, 91 (28.3%) patients have had serious complications and 28 (9.2%) of them died. Factors associated with 1-year mortality were age (OR 1.08, 95% CI 1.04 to 1.13; p<0.001), Charlson's index (OR 1.30, 95% CI 1.06 to 1.58; p=0.012), presence of bacteraemia (OR 4.02, 95% CI 1.35 to 11.99; p=0.008), antibiotic use in the previous 3 months (OR 3.32, 95% CI 1.11 to 9.87; p=0.029) and Staphylococcus aureus NJSA compared with Streptococcus sp. NJSA (OR 7.24, 95% CI 1.26 to 41.68, p=0.027). The complete recovery with no adverse joint outcome at 1 year was observed in n=125/278 patients (55.0%). CONCLUSION: Prognosis of NJSA remained severe with a high rate of morbimortality. Its management was very heterogeneous. This study highlights the importance of the new French recommendations, published after the completion of the study, in order to facilitate NJSA management.

MRI Features Associated With the Detection of Microbial Pathogens by CT-Guided Biopsy in Septic Spondylodiscitis.

OBJECTIVE: The aim of this study was to assess the magnetic resonance imaging (MRI) features associated with microbial pathogen detection by computed tomography (CT)-guided biopsy in patients with suspected septic spondylodiscitis. METHODS: For the last 10-year period, we analyzed the medical records of patients who underwent MRI and CT-guided biopsy for suspected septic spondylodiscitis. Clinical characteristics were recorded. The following MRI features were assessed: edema or contrast enhancement of the intervertebral disc, adjacent vertebrae, epidural and paravertebral space, presence of abscess, and paravertebral edema size. A positive biopsy was defined by pathogen identification on bacterial analysis or the presence of granuloma on histology. Predictors of a positive biopsy were assessed with a logistic regression model. RESULTS: We examined data for 61 patients (34 [56%] male; mean age, 59.9 ± 18.0 years); for 35 patients (57%), CT-guided biopsy was positive for a pathogen. The 4 MRI findings significantly associated with a positive biopsy were epiduritis, greater than 50% vertebral endplate edema, loss of intradiscal cleft, and abscess. The size of paravertebral edema was greater with a positive than negative biopsy (median, 15.9 [interquartile range, 11.3-21.3] vs 7.3 [4.6-12.9] mm; p = 0.004). On multivariable analysis, epiduritis was the only independent predictor of a positive biopsy (adjusted odds ratio, 7.4 [95% confidence interval, 1.7-31.4]; p = 0.006). CONCLUSIONS: Epiduritis and the size of paravertebral edema on MRI are associated with detection of a microbial pathogen in suspected septic spondylodiscitis. For patients without these MRI signs, the need for further investigations such as enriched or prolonged cultures, a second CT-guided biopsy, or even surgical biopsy need to be discussed.

Clinical characteristics and management of olecranon and prepatellar septic bursitis in a multicentre study.

BACKGROUND: No current guidelines are available for managing septic bursitis (SB). OBJECTIVES: To describe the clinical characteristics and management of olecranon and prepatellar SB in five French tertiary care centres. METHODS: This is a retrospective observational multicentre study. SB was diagnosed on the basis of positive cultures of bursal aspirate. In the absence of positive bursal fluid, the diagnosis came from typical clinical presentation, exclusion of other causes of bursitis and favourable response to antibiotic therapy. RESULTS: We included 272 patients (median age of 53 years, 85.3% male and 22.8% with at least one comorbidity). A microorganism was identified in 184 patients (67.6%), from bursal fluids in all but 4. We identified staphylococci in 135 samples (73.4%), streptococci in 35 (19%) and 10 (5.5%) were polymicrobial, while 43/223 bursal samples remained sterile (19.3%). Forty-nine patients (18%) were managed without bursal fluid analysis. Antibiotic treatment was initially administered IV in 41% and this route was preferred in case of fever (P = 0.003) or extensive cellulitis (P = 0.002). Seventy-one (26%) patients were treated surgically. A low failure rate was observed (n = 16/272, 5.9%) and failures were more frequent when the antibiotic therapy lasted <14 days (P = 0.02) in both surgically and medically treated patients. CONCLUSIONS: Despite variable treatments, SB resolved in the majority of cases even when the treatment was exclusively medical. The success rate was equivalent in the non-surgical and the surgical management groups. However, a treatment duration of <14 days may require special attention in both groups.

Pain catastrophising worsens RAPID3 in all rheumatologic conditions.

OBJECTIVES: To assess RAPID3 in various rheumatologic conditions, and the impact of pain catastrophising on RAPID3. METHODS: A set of questionnaires, including RAPID3 (0-30) and pain catastrophising score (0-52), was given to all outpatients seen in a one-month period: 518 patients fulfilled the questionnaires, including 127 RA (42% taking biologics), and 135 SpA (58% taking biologics). RESULTS: Mean pain catastrophising was 18.5±12.5, and 19% of patients could be classified as catastrophisers (>30). Higher RAPID3 scores were observed in the 33 osteoarthritis of lower limbs (16.44±5.20), 10 fibromyalgia (15.52±5.53), 47 back-pain (14.88±5.17), 17 osteoarthritis of upper limbs (13.61±7.42), and 38 tendinopathies (12.85±4.38). Lower RAPID3 were observed in the 135 SpA (12.79±6.03), 127 RA (12.18±6.30), 27 miscellaneous disorders (9.83±6.28), 7 entrapment neuropathies (9.81±4.51), 19 systemic connective tissue disorders (8.26±7.04) and 58 osteoporosis (7.85±6.95). Much higher RAPID3 scores were observed in the 19% with high pain catastrophising scores, whatever the conditions, and lower scores in the 15% with disablement benefits. RAPID3 was not associated with age or disease duration, but strongly correlated with daily fatigue, poor sleep, and length of daily pain. CONCLUSIONS: Thanks to progress made in RA and SpA treatment, higher RAPID3 scores were mostly observed in other rheumatic conditions, but co-morbidities and pain catastrophising might contribute to floor effects when assessing rheumatic disorders with RAPID3, hindering the recognition of low disease activity in some RA of SpA patients.

Multiple Vertebral Osteonecroses (Kümmell's Disease) After 10 Years on Denosumab: Is Osteocyte Apoptosis to Blame?

We report here a case of multiple vertebral osteonecroses with intrasomatic gaseous dissection (Kümmell's disease) occurring 1 year after the end of a 10-year course of denosumab treatment for osteoporosis without fractures. Histomorphometry and bone remodeling markers revealed major bone resorption and the persistence of an inhibition of bone formation. The presence of multiple empty lacunae in the bone provided evidence for high levels of osteocyte apoptosis. Osteocytes direct bone resorption (via the RANK/RANK-L/osteoprotegerin system) and formation (Wnt system, with SOST and DKK1) pathways. The vertebral osteonecrosis in our case may, therefore, have resulted from osteocyte apoptosis, decompensated by the sudden reactivation of bone remodeling after the cessation of denosumab treatment.

IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro.

OBJECTIVES: Interleukin (IL)-38 is a newly characterised cytokine that belongs to the IL-1 family. This cytokine is expressed in the rheumatoid arthritis (RA) synovial tissue and IL-38 deficient mice have exacerbated arthritis. Here, we analysed the effect of IL-38 overexpression in the joints of arthritic mice, in human macrophages and synovial fibroblasts in vitro. METHODS: Articular injections of an adeno-associated virus (AAV) 2/8 encoding IL-38 were performed in collagen-induced arthritis (CIA), K/BxN serum transfer-induced arthritis (STIA) and antigen-induced arthritis (AIA) in mice. The effect of IL-38 overexpression was evaluated through clinical scores, immunohistochemistry, microCT, Luminex and RT-qPCR analysis. THP-1 macrophages were transduced with a lentiviral vector to overexpress IL-38. RESULTS: Clinical inflammatory scores were significantly decreased after AAV IL-38 injection in joints of mice with CIA and STIA, but not AIA. This decrease was accompanied by reduced macrophage infiltration and a decreased expression of Th17 cytokines (IL-17, IL-23, IL-22) and TNFα. However, IL-38 overexpression had no effect on cartilage or bone destruction. In vitro, the THP-1 monocytic cell line expressed less IL-6, TNFα and IL-23 after IL-38 overexpression. Conditioned media from these cells, containing released IL-38, also exert an anti-inflammatory effect on human primary macrophages and synovial fibroblasts from patients with RA. CONCLUSIONS: This study shows for the first time that IL-38 overexpression attenuates the severity of experimental arthritis. IL-38 may exert its anti-inflammatory effects by decreasing the production of proinflammatory cytokines by macrophages and synovial fibroblasts. This effect can lead to the development of novel treatment strategies in arthritis.

2023 French recommendations for diagnosing and managing prepatellar and olecranon septic bursitis.

Septic bursitis (SB) is a common condition accounting for one third of all cases of inflammatory bursitis. It is often related to professional activities. Management is heterogeneous and either ambulatory or hospital-based, with no recommendations available. This article presents recommendations for managing patients with septic bursitis gathered by 18 rheumatologists from the French Society for Rheumatology work group on bone and joint infections, 1 infectious diseases specialist, 2 orthopedic surgeons, 1 general practitioner and 1 emergency physician. This group used a literature review and expert opinions to establish 3 general principles and 11 recommendations for managing olecranon and prepatellar SB. The French Health authority (Haute Autorité de santé [HAS]) methodology was used for these recommendations. Designed for rheumatologists, general practitioners, emergency physicians and orthopedic surgeons, they focus on the use of biological tests and imaging in both outpatient and inpatient management. Antibiotic treatment options (drugs and duration) are proposed for both treatment modalities. Finally, surgical indications, non-drug treatments and prevention are covered by specific recommendations.

Association between radiographic and functional outcome in vertebral osteomyelitis SPONDIMMO, a 6-month prospective multicenter cohort.

OBJECTIVES: This study aimed to describe radiographic and functional evolution over 6 months in a large cohort of VO patients. METHODS: We prospectively recruited patients with VO from 2016 to 2019 in 11 French centers. X-rays were performed at baseline, 3 months, and 6 months to assess progression using structural and static criteria. Functional impairment was evaluated using the Oswestry Disability Index (ODI) at 3 months and 6 months. RESULTS: Two hundred and twenty-two patients were included. Mean age was 67.8±14 years, mostly men (67.6%). After 3 months, there was a significant increase in vertebral fusion (16.4% vs 52.7%), destruction of vertebral bodies (10.1% vs 22.8%), and of all the static features (frontal angulation (15.2% vs 24.4%), segmental (34.6% vs 56%) and regional (24.5% vs 41%) kyphosis). From 3 to 6 months, among the different X-ray abnormalities, only the complete fusion progressed significantly (16.6% vs 27.2%). Median ODI showed significant improvement from 3 to 6 months (24, IQR [11.5-38] vs 16, IQR [6-34]). At 6 months, 14.1% of the patients had a severe disability, 2% a major disability. The persistence of vertebral destruction at 6 months was associated with a higher ODI (16, IQR [7.5-30.5] vs 27, IQR [11.5-44.5]). No differences in radiological progression were observed with immobilization using a rigid brace. CONCLUSION: Our study demonstrates structural and static radiographic progression after 3 months. Only the complete fusion progressed over the long-term. Functional impairment was associated with persistence of vertebral destruction.

Spine immobilization and neurological outcome in vertebral osteomyelitis SPONDIMMO, a prospective multicentric cohort.

OBJECTIVE: The aim of our study was to describe spine immobilization in a multicentric cohort of vertebral osteomyelitis (VO), and evaluate its association with neurological complications during follow-up. METHODS: We prospectively included patients from 2016 to 2019 in 11 centers. Immobilization, imaging, and neurological findings were specifically analyzed during a 6-month follow-up period. RESULTS: 250 patients were included, mostly men (67.2%, n=168). Mean age was 66.7±15 years. Diagnosis delay was 25 days. The lumbo-sacral spine was most frequently involved (56.4%). At diagnosis, 25.6% patients (n=64) had minor neurological signs and 9.2% (n=23) had major ones. Rigid bracing was prescribed for 63.5% (n=162) of patients, for a median of 6 weeks, with variability between centers (P<0.001). The presence of epidural inflammation and abscess on imaging was associated with higher rates of rigid bracing prescription (OR 2.33, P=0.01). Frailness and endocarditis were negatively associated with rigid bracing prescription (OR 0.65, P<0.01, and OR 0.42, P<0.05, respectively). During follow up, new minor or major neurological complications occurred in respectively 9.2% (n=23) and 6.8% (n=17) of patients, with similar distribution between immobilized and non-immobilized patients. CONCLUSION: Spine immobilization prescription during VO remains heterogeneous and seems associated inflammatory lesions on imaging but negatively associated with frailness and presence of endocarditis. Neurological complications can occur despite rigid bracing. Our data suggest that in absence of any factor associated with neurological complication spine bracing might not be systematically indicated. We suggest that spine immobilization should be discussed for each patient after carefully evaluating their clinical signs and imaging findings.

Minocycline Combined with Vancomycin for the Treatment of Methicillin-Resistant Coagulase-Negative Staphylococcal Prosthetic Joint Infection Managed with Exchange Arthroplasty.

Introduction: Treatment of methicillin-resistant (MR) staphylococcal prosthetic joint infections (PJIs) remains a matter of discussion, with vancomycin-rifampin combination therapy being the preferred treatment for DAIR and one-stage exchange arthroplasty strategies. This study analyzes the outcomes of patients with chronic methicillin-resistant coagulase-negative staphylococcal PJIs treated with vancomycin-minocycline combination therapy. Methods: This prospective, single center cohort study included all chronic MR coagulase-negative staphylococcal PJIs (01/2004-12/2014) treated with exchange arthroplasty and at least 4 weeks of minocycline-vancomycin. The following endpoints were considered: reinfection including relapse (same microorganism) and a new infection (different microorganism) and PJI-related deaths. Their outcomes were compared with PJIs treated with rifampin-vancomycin during the same period. Results: Thirty-four patients (median age, 69 years) with 22 hip and 12 knee arthroplasty infections were included. Sixteen (47%) had previously been managed in another center. Median vancomycin MIC of strains was 3 mg/L. Nineteen underwent one-stage, 15 two-stage exchange arthroplasty. After a median [IQR] follow-up of 43 [26-68] months, 2 patients relapsed and 6 developed a new PJI. Compared to 36 rifampin-vancomycin treated PJIs, relapse- or reinfection-free survival rates didn't differ, but more new infections developed in the minocycline group (6 vs 3; P 0.3). Conclusions: Minocycline-vancomycin combination therapy for chronic MR coagulase-negative staphylococcal PJIs seems to be an interesting therapeutic alternative.

2020 French recommendations on the management of septic arthritis in an adult native joint.

Septic arthritis (SA) in an adult native joint is a rare condition but a diagnostic emergency due to the morbidity and mortality and the functional risk related to structural damage. Current management varies and the recommendations available are dated. The French Rheumatology Society (SFR) Bone and Joint Infection Working Group, together with the French Language Infectious Diseases Society (SPILF) and the French Orthopaedic and Trauma Surgery Society (SOFCOT) have worked according to the HAS methodology to devise clinical practice recommendations to diagnose and treat SA in an adult native joint. One new focus is on the importance of microbiological documentation (blood cultures and joint aspiration) before starting antibiotic treatment, looking for differential diagnoses (microcrystal detection), the relevance of a joint ultrasound to guide aspiration, and the indication to perform a reference X-ray. A cardiac ultrasound is indicated only in cases of SA involving Staphylococcus aureus, oral streptococci, Streptococcus gallolyticus or Enterococcus faecalis, or when infective endocarditis is clinically suspected. Regarding treatment, we stress the importance of medical and surgical collaboration. Antibiotic therapies (drugs and durations) are presented in the form of didactic tables according to the main bacteria in question (staphylococci, streptococci and gram-negative rods). Probabilistic antibiotic therapy should only be used for patients with serious symptoms. Lastly, non-drug treatments such as joint drainage and early physical therapy are the subject of specific recommendations.

Isolation of Coxiella burnetii from an acromioclavicular infection with low serological titres.

Coxiella burnetii acromioclavicular infection is a new infectious focus, evidenced here for the first time using the gold standard, culture. Positron emission tomography had a crucial role in identifying the deep infectious focus, even when C. burnetii serological titres were low.

Bilateral Pulmonary Embolism Following a Viper Envenomation in France: A Case Report and Review.

Complications following snake bites are not common in France. We report the case of a bilateral pulmonary embolism following a viper envenomation in France.A healthy 72-year-old female presented with a lower limb hematoma following a viper bite. She was admitted at the hospital 2 days later and received low-molecular-weight heparin because of bed rest. Seven days later, she complained of thoracic pain and respiratory failure, and a bilateral pulmonary was diagnosed, without biological sign of neither disseminated intravascular coagulation nor coagulation trouble. Repeated lower limbs Doppler ultrasound were normal.This case is particularly interesting because it is only the 7th reported case of pulmonary embolism following a snake envenomation; moreover, it happened in France where poisonous snakes are very rare.Several hypotheses have been made to explain this late localized coagulopathy: an increased level of unstable fibrin produced by thrombin-like glycoproteins from the venom is one of them.

Success Rate and Utility of Ultrasound-guided Synovial Biopsies in Clinical Practice.

OBJECTIVE: The utility of synovial biopsy in increasing our understanding of the pathogenesis of inflammatory arthropathies, as well as in evaluating treatments, is well established. Ultrasound (US) allows synovial assessment and therefore assists in biopsying synovial tissue in a safe and well-tolerated manner. This study's objectives were to (1) determine the rate of success in retrieving synovial tissue using US guidance, (2) describe the indications for US-guided synovial biopsies in the clinical setting, (3) determine how frequently the synovial biopsy can lead to a clear diagnosis, and (4) assess the quality of the synovial tissue obtained using this technique. METHODS: Synovial biopsies of small and large joints were performed under US guidance between February 2007 and December 2014 using a semiautomatic core biopsy needle. The biopsy procedure was considered successful if synovial tissue was found at histological examination. RESULTS: Seventy-four patients with undifferentiated arthritis underwent 76 synovial biopsies. The success rate in retrieving synovial tissue was 81.6% (62/76). One patient taking acetyl salicylic acid at 75 mg at the time of the biopsy presented with hemarthrosis 48 h after the procedure, which resolved following simple arthrocentesis. A definitive diagnosis was achieved in 16% of the patients where synovial tissue was sampled successfully. CONCLUSION: US-guided synovial biopsies in clinical practice can be performed safely on patients with undifferentiated arthritis and with heterogeneous presentations. The rate of success in acquiring synovial tissue is high. The procedure usually retrieves quality tissue and leads to a definite diagnosis in a significant minority of patients.

Is There an Association Between Magnetic Resonance Imaging and Neurological Signs in Patients With Vertebral Osteomyelitis?: A Retrospective Observational Study on 121 Patients.

Neurological complications can occur in up to 51% of vertebral osteomyelitis (VO) in surgical series. The aim of our study was to estimate the frequency of neurological signs in a nonselected population of patients with VO and to assess clinical and MRI changes associated with these complications.We reviewed medical charts of patients with VO from 2007 to 2014 in our University Hospital and their MRIs were analyzed by a radiologist blinded from clinical data. Neurological status was defined as follow: normal, minor signs (radiculalgia or sensory loss), and major signs (motor deficit and/or sphincter dysfunction).A total of 121 patients were included. Mean age was 64.3 years. Overall, 50 patients (40%) had neurological signs, 26 were major signs (21.5%). Neurological signs were present at the time of admission in 37 patients and happened secondarily in 13 cases. MRI changes associated with major neurological signs were: Cervical involvement (P = 0.011), dural sac compression (P = 0.0012), ventral effacement of the subarachnoidal space (P < 0.001), compressive myelopathy (P = 0.006). More than 50% of the vertebral body destruction (P = 0.017), angular kyphosis (P = 0.016) partial or complete destruction of posterior arch (P = 0.032) were also associated with these signs. Neither epidural abscesses, multifocal lesions, loss of disk height, nor nerve roots compression were associated with major neurological signs.Neurological signs occurred in 40% of our patients with one half being major signs. Cervical involvement, vertebral destruction, angular kyphosis, dural compression, effacement of subarachnoid space and compressive myelopathy on MRI were risk factors associated with neurological complications.

Usefulness of a pre-procedure ultrasound scanning of the lumbar spine before epidural injection in patients with a presumed difficult puncture: A randomized controlled trial.

UNLABELLED: Ultrasound (US) is widely used in rheumatology to study and guide injection of peripheral joints. It can also provide useful information about the anatomy of the lumbar spine. Studies have shown that US examination of the spine was a useful tool to help perform epidural anaesthesia. The purpose of the study was to determine if the selection of the optimum puncture level by US may facilitate epidural steroid injection in case of presumed difficult puncture (BMI>30 kg/m(2), age>60 years or lumbar scoliosis). METHODS: We performed a prospective randomized controlled study. Eighty patients were randomized in two groups: US group (n=40) which underwent a pre-procedure spinal US to determine the optimal lumbar level for injection or control group (n=40) for which the level of injection was determined by palpation. Primary endpoint was the pain during the procedure assessed using the Visual Analogue Scale (VAS). RESULTS: We found a positive correlation between depth of the epidural space and BMI (P<0.001) and a negative correlation between size of the interspinous spaces and age (P<0.01). Visibility of the epidural space was not altered by obesity or age. We observed a trend toward a reduction in pain intensity during the procedure in the US group compared to the control group with a mean difference at -0.94 [-1.90; 0.02] but the difference was not significant (P=0.054). CONCLUSION: US of the lumbar spine was feasible in patients with lumbar conditions even in obese and old ones and allowed the visualization of the epidural space. However, pre-procedure US examination did not reduce pain during the procedure.