Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide

INTRODUCTION: Mechanical ventilation (MV) could prime the lung toward an inflammatory response if exposed to another insult such as bacterial invasion. The underlying mechanisms are not so far clear. Toll-like receptors (TLRs) allow the host to recognize selectively bacterial pathogens and in turn to trigger an immune response. We therefore hypothesized that MV modulates TLR2 expression and in turn modifies responsiveness to agonists such as bacterial lipopeptide (BLP). METHOD: Both in vitro and in vivo experiments were conducted. First, TLR2 expression and protein were measured in the A549 pulmonary epithelial cell line submitted to 8-hour cyclic stretch (20% elongation; 20/minute rate). After a 24-hour period of cyclic stretch, the inflammatory response of the A549 cells to the synthetic BLP, Pam(3)CSK(4), was tested after 8 hours of exposure. In a second set of experiments, healthy anesthetized and paralyzed rabbits were submitted to 8-hour MV (tidal volume = 12 ml/kg, zero end-expiratory pressure; FIO(2 )= 50%; respiratory rate = 20/minute) before being sacrificed for TLR2 lung expression assessment. The lung inflammatory response to BLP was then tested in animals submitted to 24-hour MV before being sacrificed 8 hours after the tracheal instillation of Pam(3)CSK(4). RESULTS: Cyclic stretch of human pulmonary epithelial cell lines increased both TLR2 mRNA and protein expression. Cells submitted to cyclic stretch also increased IL-6 and IL-8 secretion in response to Pam(3)CSK(4), a classical TLR2 ligand. A mild-stretch MV protocol induced a 60-fold increase of TLR2 mRNA expression in lung tissue when compared with spontaneously breathing controls. Moreover, the combination of MV and airway exposure to Pam(3)CSK(4 )acted synergistically in causing lung inflammation and injury. CONCLUSIONS: Mild-stretch MV increases lung expression of TLR2 and sensitizes the lung to bacterial TLR2 ligands. This may account for the propensity of mechanically ventilated patients to develop acute lung injury in the context of airway bacterial colonization/infection

Real-Time PCR for Diagnosis of Oculoglandular Tularemia

International audienc

Acute bacterial prostatitis: heterogeneity in diagnostic criteria and management. Retrospective multicentric analysis of 371 patients diagnosed with acute prostatitis

<p>Abstract</p> <p>Background</p> <p>There is currently a lack of consensus for the diagnosis, investigations and treatments of acute bacterial prostatitis (AP).</p> <p>Methods</p> <p>The symptoms, investigations and treatments of 371 inpatients diagnosed with AP were analyzed through a retrospective study conducted in four departments – Urology (U), Infectious Diseases (ID), Internal Medicine (IM), Geriatrics (G) – of two French university hospitals.</p> <p>Results</p> <p>The cause of admission, symptoms, investigations and treatments depended markedly on the department of admission but not on the hospital. In U, patients commonly presented with a bladder outlet obstruction, they had a large imaging and functional check-up, and received alpha-blockers and anti-inflammatory drugs. In ID, patients were febrile and received longer and more appropriate antibiotic treatments. In G, patients presented with cognitive disorders and commonly had post-void urine volume measurements. In IM, patients presented with a wide range of symptoms, and had very diverse investigations and antibiotic regimen.</p> <p>Overall, a 3:1 ratio of community-acquired AP (CA-AP) to nosocomial AP (N-AP) was observed. Urine culture isolated mainly <it>E. coli </it>(58% of AP, 68% of CA-AP), with venereal agents constituting less than 1%. The probabilistic antibiotic treatments were similar for N-AP and CA-AP (58% bi-therapy; 63% fluoroquinolone-based regimen). For N-AP, these treatments were more likely to be inadequate (42% <it>vs. </it>8%, p < 0.001) and had a higher rate of bacteriological failure (48% <it>vs. </it>19%, p < 0.001).</p> <p>Clinical failure at follow-up was more common than bacteriological failure (75% versus 24%, p < 0.001). Patients older than 49 had more underlying urinary tract disorders and a higher rate of clinical failure (30% versus 10%, p < 0.0001).</p> <p>Conclusion</p> <p>This study highlights the difficulties encountered on a daily basis by the physicians regarding the diagnosis and management of acute prostatitis.</p

Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

Pneumococcies : le fardeau est-il toujours aussi lourd ?

EA MERS CT3 Enjeu 3International audienceThe death rate of invasive pneumococcal infections decreased by 100 fold in one century. This tremendous improvement was due mainly to antibiotic use and multiple attempts at antipneumococcal vaccinations; thus, this was true only for developed countries. However, in France, the incidence has increased, over the last 10 years, in all age classes except for children vaccinated by the heptavalent pneumococcal conjugate vaccine. The incidence of these infections remains high, when associated to some risk factors such as HIV infection, malignant blood diseases, solid cancers, bronchial diseases, or alcohol abuse. The pneumococcal vaccine should be prescribed first to patients with those risk factors. A change of serotypes distribution has been observed in children with a decrease of vaccine serotypes and predominance of related or non-vaccine serotypes. This reflects the effectiveness of vaccination and the need of to regularly update the vaccine. Thus, pneumococcal infections have been increasing and vaccination should be more widely proposed.Le taux de mortalité des infections invasives à pneumocoque a diminué d’au moins un facteur 100 en un siècle. Cette amélioration considérable est, principalement, à mettre sur le compte à la fois de l’antibiothérapie et des multiples tentatives vaccinales ; cela ne s’applique donc qu’aux pays développés. Cependant, l’incidence a, en France, en ces dix dernières années, augmenté dans toutes les classes d’âge sauf chez les enfants vaccinés par vaccin à sept valences. L’incidence de ces infections reste très élevée en association à certains facteurs de risques : infection VIH, hémopathies malignes, cancers solides, bronchopathie, alcool. La vaccination antipneumococcique devrait être proposée en priorité dans ces populations. Chez les enfants, la répartition des sérotypes a évolué avec diminution des sérotypes vaccinaux et prédominance des sérotypes apparentés ou non vaccinaux. Cette évolution montre l’efficacité vaccinale et la nécessité d’une adaptation plus ou moins régulière du vaccin. Les infections pneumococciques sont donc en augmentation et la vaccination doit être plus largement proposée

Evaluation des consultations informelles en infectiologie au Centre Hospitalier Universitaire de Dijon

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Facteurs favorisant la transition mucoïde de pseudomonas aeruginosa chez les sujets atteints de mucoviscidose (à propos de 55 patients au Centre de Ressources et de Compétences de la Mucoviscidose de Dijon)

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Efficacité et observance du traitement antirétroviral à Tokombéré, province de l'Extrème-Nord Cameroun

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Enquête sur la pratique vaccinale anti-meningoccique C auprès des médecins généralistes et pédiatres de Dijon et agglomération dijonnaise

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude du comportement prophylaxique et thérapeutique des médecins généralistes face à une morsure de tique en Bresse et région Chalonnaise

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF