93 research outputs found
Analysis of superantigenic toxin Vβ T-cell signatures produced during cases of staphylococcal toxic shock syndrome and septic shock
No full textABSTRACTMost clinical isolates of Staphylococcus aureus harbour genes encoding superantigenic toxins that bind the Vβ domain of T-cells, but little information is available concerning superantigenic toxin production during staphylococcal toxic shock syndrome (TSS) and septic shock. This prospective study investigated 14 patients with staphylococcal TSS or septic shock; the toxin gene profile of each isolate was determined and flow-cytometry was used to identify the discriminant Vβ signature (DVβS) of each superantigenic toxin in vitro. Attempts were also made to identify in-vivo production of superantigenic toxin DVβS in patients’ blood. The DVβS identified in vitro were: toxic shock syndrome toxin (TSST)-1, Vβ 2; staphylococcal enterotoxin (SE), Vβ 9, Vβ 22; SEB, Vβ 3, Vβ 14, Vβ 17; SED, Vβ 1, Vβ 8; egc, Vβ 5.3, Vβ 7.1, Vβ 9, Vβ 23; and SE/K, Vβ 5.1. The DVβS of TSST-1 and SEB were detected in patients with menstrual and non-menstrual TSS, respectively, whereas no Vβ signature was detected during septic shock. All patients with septic shock (but only one patient with TSS) had lymphopenia and/or impaired cellular immunity. Detection of a superantigenic toxin DVβS may help to show which toxin is produced during staphylococcal TSS, thus confirming the diagnosis and hastening the administration of anti-toxin therapy. In contrast, this approach failed to demonstrate superantigenic toxin involvement in cases of septic shock. In this latter condition, a superantigenic toxin may not be produced by S. aureus, or its production may occur without expansion of targeted T-cells because of T-cell apoptosis and/or anergy
Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients
No full textInternational audienceThe mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (\textgreater or \textless 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2\textperiodcentered339, P = 0\textperiodcentered001, and OR = 0\textperiodcentered803, P = 0\textperiodcentered041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort
Chronic Propionibacterium acnes prosthesis joint infection manifesting as a large abscess with gas, without prosthesis loosening
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Metallosis-associated prosthetic joint infection
No full textTotal joint replacement is the standard treatment of advanced osteoarthritis. Metal-on-Metal (MoM) hip resurfacing and hip arthroplasty are associated with long durability and low rates of dislocations and used to be the standard surgical treatments. Complications due to MoM prostheses have however been widely reported [1]. Adverse reactions to metal debris (ARMD) such as metallosis result from the progressive degradation of the metal surface and from metal ions deposition in the surrounding tissues. The formation of “pseudotumors” leading to prosthe- sis malfunction has been reported after MoM resurfacing. Total arthroplasty can also lead to the infection of the prosthesis as a consequence of contamination during surgery or bacteremic infection not related to the prosthesis. Infections remain quite common (1–3% of surgical procedures) but reports of associ- ated ARMD are limited. We report the case of three patients presenting with metallosis-associated infection on joint pros- thesis
Teicoplanin-based antimicrobial therapy in Staphylococcus aureus bone and joint infection: Tolerance, efficacy and experience with subcutaneous administration
Get PDFBackground: Staphylococci represent the first etiologic agents of bone and joint infection (BJI), leading glycopeptides use, especially in case of methicillin-resistance or betalactam intolerance. Teicoplanin may represent an alternative to vancomycin because of its acceptable bone penetration and possible subcutaneous administration. Methods: Adults receiving teicoplanin for S. aureus BJI were included in a retrospective cohort study investigating intravenous or subcutaneous teicoplanin safety and pharmacokinetics. Results: Sixty-five S. aureus BJIs (orthopedic device-related infections, 69 %; methicillin-resistance, 17 %) were treated by teicoplanin at the initial dose of 5.7 mg/kg/day (IQR, 4.7-6.5) after a loading dose of 5 injections 12 h apart. The first trough teicoplanin level (Cmin) reached the therapeutic target (15 mg/L) in 26 % of patients, only. An overdose (Cmin >25 mg/L) was observed in 16 % patients, 50 % of which had chronic renal failure (p = 0.049). Seven adverse events occurred in 6 patients (10 %); no predictive factor could be highlighted. After a 91-week follow-up (IQR, 51-183), 27 treatment failures were observed (42 %), associated with diabetes (OR, 5.1; p = 0.057), systemic inflammatory disease (OR, 5.6; p = 0.043), and abscess (OR, 4.1; p < 10 -3). A normal CRP-value at 1 month was protective (OR, 0.2; p = 0.029). Subcutaneous administration (n = 14) showed no difference in pharmacokinetics and tolerance compared to the intravenous route. Conclusions: Teicoplanin constitutes a well-tolerated therapeutic alternative in S. aureus BJI, with a possible subcutaneous administration in outpatients. The loading dose might be increase to 9-12 mg/kg to quickly reach the therapeutic target, but tolerance of such higher doses remains to be evaluated, especially if using the subcutaneous route
Post-traumatic chronic bone and joint infection caused by Butyricimonas spp, and treated with high doses of ertapenem administered subcutaneously in a 30-year-old obese man
Get PDFAn obese but otherwise healthy 30-year-old man presented with septic pseudarthrosis following a post-traumatic open radial fracture. Three months earlier, the patient had been involved in a truck accident and suffered a distal open radial fracture associated with compartment syndrome ( figure 1A). Primary management consisted of wound debridement, fasciotomy, stabilisation with external fixation and antibiotic prophylaxis with amoxicillin-clavulanate. The wound healed after 1 month ( figure 1B). Due to pseudarthrosis ( figure 1C, D), the patient returned to the operating room for internal fixation. He did not have fever, and there was no local sign of inflammation and no fistula; C reactive protein was <5 mg/L. Internal fixation was not performed, as a bone abscess in
the facture site was discovered. Surgical samples revealed Bacteroides vulgatus, Clostridium tertium and Butyricimonas spp in cultures. MRI revealed several abscesses in the radius (figure 1E). As the patient refused central vascular access, he received prolonged high doses of ertapenem subcutaneously (1 g two times a day) for 3 months, with metro- nidazole during the first month, followed by clinda- mycin. The ertapenem (diluted in 50cc of physiological serum) was infused subcutaneously by butterfly disposable needle in the lower quadrants of the abdomen and alternately on the anterior side of a thigh ( figure 1F, G) during a 30–60 min gravity infusion. Arthrodesis was then performed and the outcome was favourable (figure 1H)
Disappearance of FDG uptake on PET scan after antimicrobial therapy could help for the diagnosis of Coxiella burnetii spondylodiscitis.
Get PDFA 55 year-old man was admitted for worsening of a chronic low back pain associated with L4-L5 anterolisthesis, despite taking non-steroidal anti-inflammatory drugs for several months. He had a medical history of high blood pressure and obesity (body mass index, 37 kg/m2). He lived in the countryside but had no direct contact with animals except his dog. There were no fever, chills, sweats or weight loss. C reactive protein (CRP) was <2.9 mg/L. Radiographs showed L4-L5 anterolisthesis with endplate erosions and bony sclerosis (figure 1A). On MRI (figure 1B), there was a significant enhancement of L4-L5 vertebral endplates and paravertebral soft tissues. Positron emission tomography (PET) CT scan showed an intense uptake of the L4-L5 space (figure 1C). Blood and CT-guided discovertebral cultures remained sterile (including for mycobacteria) and 16s PCR and in-house specific Coxiella burnetii PCR were negative. C. burnetii serology (Focus diagnostics Q fever immunofluorescent antibody IgG and IgM test kits) was positive and in favour of a chronic Q fever (phase I, IgG 2048; phase II, IgG 4096; IgM were negative). Brucella and Bartonella were negative. An echocardiogram was performed to exclude vegetations caused by bacterial endocarditis. The patient was treated with doxycycline (200 mg/day) and hydroxychloroquine (400 mg/day) for 10 months. A significant improvement with reduction of the back pain was noticed and the CRP remained <2.9 mg/L. The antibody titres decreased and the pathological uptake of the L4-L5 space on PET scan disappeared when antibiotics were stopped (figure 1D)
Pristinamycin in the treatment of MSSA bone and joint infection-authors' response
Get PDFObjectives: The aim of this study was to evaluate pristinamycin in the treatment of MSSA bone and joint infection (BJI).
Patients and methods: A retrospective, single-centre cohort study (2001–11) investigated outcome in adults receiving pristinamycin for MSSA BJI and pristinamycin-related adverse events (AEs).
Results: One hundred and two MSSA BJIs were assessed in 98 patients [chronic infection, 33.3%; and orthopaedic device-related infection (ODI), 67.6%]. Surgery was performed in 77.5% of total cases, and in all but three ODIs, associated with antibiotic therapy of a median total duration of 29.2 weeks. Pristinamycin was prescribed as a part of the initial intensive treatment phase (29.4%) and/or included in final maintenance therapy (83.3%) at a dose of 47.6 (45.5–52.6) mg/kg/day for 9.3 (1.4–20.4) weeks. AEs occurred in 13.3% of patients, consisting of gastrointestinal disorder (76.9%) or allergic reaction (23.1%), leading to treatment interruption in 11 cases. AEs were related to daily dose (OR, 2.733 for each 10 additional mg/kg/day; P1⁄40.049). After a follow-up of 76.4 (29.6–146.9) weeks, the failure rate was 34.3%, associated with ODI (OR, 4.421; P1⁄40.006), particularly when the implant was retained (OR, 4.217; P1⁄40.007). In most patients, the pristinamycin companion drug was a fluoroquinolone (68.7%) or rifampicin (21.7%), without difference regarding outcome.
Conclusions: Pristinamycin is an effective, well-tolerated alternative therapeutic option in MSSA BJI, on condition that a daily dosage of 50 mg/kg is respected
Delta-toxin production deficiency in Staphylococcus aureus: A diagnostic marker of bone and joint infection chronicity linked with osteoblast invasion and biofilm formation
Get PDFBiofilm formation, intra-osteoblastic persistence, small-colony variants (SCVs) and the dysregulation of agr, the major virulence regulon, are possibly involved in staphylococcal bone and joint infection (BJI) pathogenesis. We aimed to investigate the contributions of these mechanisms among a collection of 95 Staphylococcus aureus clinical isolates from 64 acute (67.4%) and 31 chronic (32.6%) first episodes of BJI. The included isolates were compared for internalization rate, cell damage and SCV intracellular emergence using an exvivo model of human osteoblast infection. Biofilm formation was assessed in a microbead immobilization assay (BioFilm Ring test). Virulence gene profiles were assessed by DNA microarray. Seventeen different clonal complexes were identified among the screened collection. The staphylococcal internalization rate in osteoblasts was significantly higher for chronic than acute BJI isolates, regardless of the genetic background. Conversely, no differences regarding cytotoxicity, SCV emergence, biofilm formation and virulence gene distribution were observed. Additionally, agr dysfunction, detected by the lack of delta-toxin production using whole-cell matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis (n=15; 15.8%), was significantly associated with BJI chronicity, osteoblast invasion and biofilm formation. These findings provide new insights into MSSA BJI pathogenesis, suggesting the correlation between chronicity and staphylococcal osteoblast invasion. This adaptive mechanism, along with biofilm formation, is associated with agr dysfunction, which can be routinely assessed by delta-toxin detection using MALDI-TOF spectrum analysis, possibly providing clinicians with a diagnostic marker of BJI chronicity at the time of diagnosis
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