Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent ...dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Strict anaerobes are undeniably important residents of the cystic fibrosis (CF) lung but are still unknowns. The main objectives of this study were to describe anaerobic bacteria diversity in CF ...airway microbiota and to evaluate the association with lung function. An observational study was conducted during eight months. A hundred and one patients were enrolled in the study, and 150 sputum samples were collected using a sterile sample kit designed to preserve anaerobic conditions. An extended-culture approach on 112 sputa and a molecular approach (quantitative PCR targeting three of the main anaerobic genera in CF lung: Prevotella, Veillonella, and Fusobacterium) on 141 sputa were developed. On culture, 91.1% of sputa were positive for at least one anaerobic bacterial species, with an average of six anaerobic species detected per sputum. Thirty-one anaerobic genera and 69 species were found, which is the largest anaerobe diversity ever reported in CF lungs. Better lung function (defined as Forced Expiratory Volume in one second > 70%) was significantly associated with higher quantification of Veillonella. These results raise the question of the potential impact of anaerobes on lung function.
We aimed to characterize diagnosis, management, and outcome of Mycobacterium tuberculosis prosthetic joint infections (PJI).
Cases of M. tuberculosis PJI documented in 7 referral French centers were ...retrospectively reviewed. Data were collected from medical files on a standardized questionnaire. We performed a literature review using the keywords ‘prosthetic joint’, and ‘tuberculosis’.
During years 1997–2016, 13 patients (8 males, 5 females, median age 79 years range, 60–86) had documented M. tuberculosis PJI, involving hip (n = 6), knee (n = 6), or shoulder (n = 1). Median time from arthroplasty to diagnosis was 9 years 0.4–20. The diagnosis was obtained on joint aspirates (n = 9), or synovial tissue (n = 4). PCR was positive in all cases tested (5/5). Median duration of antituberculosis treatment was 14 months 6–32). Nine patients underwent surgery: debridement (n = 4), resection arthroplasty (n = 3), and revision arthroplasty (1-stage exchange, n = 2). PJI was controlled in 12 patients. Seventeen additional cases of documented M. tuberculosis PJI have been reported, with a favorable outcome in 79% (11/14) of patients with no surgery, 85% (11/13) with debridement, 86% (19/22) with revision arthroplasty, and 81% (17/21) with resection (NS).
M. tuberculosis PJI can be controlled with prolonged antituberculosis treatment in most cases, with or without surgical treatment.
Behçet disease (BD) is a systemic vasculitis involving vessels from any size with various clinical features. Most BD cases are multifactorial and associated with the HLA B51 antigen. In rare and ...severe early onset cases, dominant Mendelian transmission has been linked to mutations in the TNFAIP3 gene encoding A20. Herein, we propose a systematic review of the literature about the haploinsufficiency A20 (HA20) published cases.
Our review of the 45 cases of HA20 from literature highlights the similarities and the differences between this genetic auto-inflammatory disease and classical BD. HA20 looks like BD if we consider recurrent oral (87%) and genital (67%) ulcers, arthralgia or arthritis (42%), skin involvement (53%) such as erythema nodosum or abdominal symptoms (60%) such as abdominal pain, digestive ulcers or diarrhea. However, HA20 differs from classical BD because its geographical distribution is ubiquitous, sex ratio is inversed (one man for two women), first symptoms occur in early childhood (median age = 5.5 years; interquartile range: 1–10) instead of adulthood, recurrent fever is common (62%) unlike classical BD, HLA B51 antigen is uncommon and abdominal symptoms are over-represented compared to classical BD. In addition, response to colchicine in HA20 is inconstant (24%) unlike classical BD.
High fever flares and digestive involvement starting in early childhood seem to be hallmarks of HA20 clinical features. Response to colchicine is unpredictable and biotherapies like anti-TNFα and anti IL1 appear to be treatments of choice, like for other auto-inflammatory diseases. Prospective description of larger cohort of HA20 cases is needed to understand better when this disease must be looked for and how to treat these patients.
•In sporadic or familial history of early onset BD, consider HA20.•In early onset recurrent febrile abdominal features suggesting IBD, think HA20.•Colchicine, methotrexate and anti-TNFα seem to be the best current therapeutic options.•The best of knowledge is yet to come in this polymorphous genetic disease.
•A multicenter, double-blind, placebo-controlled, dose-ranging phase 2 study.•Designed to evaluate the safety and effects of roscovitine.•In Pseudomonas aeruginosa infected adult CF ...patients.•Carrying two CF causing mutations (at least one F508del-CFTR mutation).•And harboring a FEV1>40%.
The orally available kinase inhibitor R-roscovitine has undergone clinical trials against various cancers and is currently under clinical evaluation against Cushing disease and rheumatoid arthritis. Roscovitine displays biological properties suggesting potential benefits in CF: it partially corrects F508del-CFTR trafficking, stimulates the bactericidal properties of CF alveolar macrophages, and displays anti-inflammatory properties and analgesic effects.
A phase 2 trial study (ROSCO-CF) was launched to evaluate the safety and effects of roscovitine in Pseudomonas aeruginosa infected adult CF patients carrying two CF causing mutations (at least one F508del-CFTR mutation) and harboring a FEV1 ≥40%. ROSCO-CF was a multicenter, double-blind, placebo-controlled, dose-ranging study (200, 400, 800 mg roscovitine, orally administered daily for 4 days/week/4 weeks).
Among the 34 volunteers enrolled, randomization assigned 11/8/8/7 to receive the 0 (placebo)/ 200/400/800 mg roscovitine doses, respectively. In these subjects with polypharmacy, roscovitine was relatively safe and well-tolerated, with no significant adverse effects (AEs) other than five serious AEs (SAEs) possibly related to roscovitine. Pharmacokinetics of roscovitine were rather variable among subjects. No significant efficacy, at the levels of inflammation, infection, spirometry, sweat chloride, pain and quality of life, was detected in roscovitine-treated groups compared to the placebo-treated group.
Roscovitine was relatively safe and well-tolerated in CF patients especially at the 200 and 400 mg doses. However, there were 5 subject withdrawals due to SAEs in the roscovitine group and none in the placebo group. The lack of evidence for efficacy of roscovitine (despite encouraging cellular and animal results) may be due to high pharmacokinetics variability, short duration of treatment, and/or inappropriate dosing protocol.
Objectives
Prosthetic vascular graft infection (PVGI) is a very severe disease. We aimed to determine the factors associated with treatment failure.
Methods
Patients admitted to two University ...Hospitals with PVGI were included in this retrospective study. PVGI was classified as possible, probable or proven according to an original set of diagnostic criteria. We defined treatment failure if one of the following events occurred within the first year after PVGI diagnosis: death and infection recurrence due to the same or another pathogen.
Results
One hundred and twelve patients were diagnosed with possible (
n
= 26), probable (
n
= 22) and proven (
n
= 64) PVGI. Bacterial documentation was obtained for 81% of patients. The most frequently identified pathogen was
Staphylococcus aureus
(
n
= 39). Surgery was performed in 96 patients (86%). Antibiotics were administered for more than 6 weeks in 41% of patients. Treatment failure occurred in 30 patients (27.5%). The factors associated with a lower probability of treatment failure were total removal of the infected graft (OR = 0.2, 95% CI 0.1–0.6), rifampicin administration (OR = 0.3 0.1–0.9) and possible PVGI according to the GRIP criteria (OR = 0.3 0.1–0.9).
Conclusions
Treatment failure occurred in 27.5% of patients with PVGI. Total removal of the infected graft and rifampicin administration were associated with better outcomes.
The objective was to evaluate concordance between 2002 American-European Consensus Group (AECG) and 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) ...classification criteria for primary Sjögren's syndrome (pSS) and to assess how salivary gland ultrasonography (SGUS) might improve the classification of patients.
Patients with suspected pSS underwent a standardised evaluation, including SGUS, at inclusion into the single-centre Brittany DIApSS cohort. Agreement between the two criteria sets was assessed using Cohen's κ coefficient. Characteristics of discordantly categorised patients were detailed.
We prospectively included 290 patients between 2006 and 2016, among whom 125 (43%) met ACR/EULAR criteria and 114 (39%) also met AECG criteria; thus, 11 (4%) patients fulfilled only ACR/EULAR, no patients AECG only, and 165 (57%) patients neither criteria set. Concordance was excellent (κ = 0.92). Compared to patients fulfilling both criteria sets, the 11 patients fulfilling only ACR/EULAR criteria had similar age and symptom duration but lower frequencies of xerophthalmia and xerostomia (p < 0.01 for each) and salivary gland dysfunction (p < 0.01); most had systemic involvement (91%), including three (27%) with no sicca symptoms; 91% had abnormal salivary gland biopsy and 46% anti-Sjögren's-syndrome-related antigen A (anti-SSA); 64% were diagnosed with pSS by the physician. SGUS was abnormal in 12% of the 165 patients fulfilling no criteria set. Including SGUS among the ACR/EULAR criteria increased sensitivity from 87.4% to 91.1% when physician diagnosis was the reference standard.
Agreement between AECG and ACR/EULAR criteria sets is excellent. ACR/EULAR criteria are slightly more sensitive and classified some patients without sicca symptoms as having pSS. Including SGUS in the ACR/EULAR criteria may further improve their sensitivity.
•First feasibility study of respiratory viral detection in Cystic Fibrosis sputum.•High concordance between sputum and nasopharyngeal samples in viral.•Multiplex-PCR performed in 30 paired samples: ...83% viral congruency.•Sputum: an optimal non-invasive sample for viral diagnosis in cystic fibrosis.
Viruses are important agents in lung function deterioration in Cystic Fibrosis (CF). To date, no standard operating procedures (SOPs) have been established to determine which sampling method is the most effective for an optimal virological diagnosis of respiratory viral infections in CF. Here we investigated the performances of two sampling sites, sputum samples versus nasopharyngeal (NP) swabs, for thirty participants from three CF centres presenting an acute respiratory infection. Sputum and NP samples were simultaneously collected and multiplex PCR targeting 16 to 18 viruses were performed. Viruses were detected for 18/30 patients (60%). A high concordance between the sputum and NP samples was observed in 25 (83%) paired samples of which 13 tested positive and 12 tested negative. These results highlighted the relevance of sputum sampling for diagnostic of respiratory viruses in CF, which is less invasive and better accepted by CF patients than NP, and allows accurate bacterial detection.
Increasing resistance to antibiotics of Pseudomonas aeruginosa leads to therapeutic deadlock and alternative therapies are needed. We aimed to evaluate the effects of Lactobacillus clinical isolates ...in vivo, through intranasal administration on a murine model of Pseudomonas aeruginosa pneumonia. We screened in vitro 50 pulmonary clinical isolates of Lactobacillus for their ability to decrease the synthesis of two QS dependent-virulence factors (elastase and pyocyanin) produced by Pseudomonas aeruginosa strain PAO1. These results demonstrate that intranasal priming with lactobacilli acts as a prophylaxis, and avoids fatal complications caused by Pseudomonas aeruginosa pneumonia in mice. These results were independent of in vitro anti-Pseudomonas aeruginosa activity on QS-dependent virulence factors. Further experiments are required to identify the immune mechanism before initiating clinical trials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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