41 research outputs found

    e-Pilly TROP Maladies infectieuses tropicales

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    L’e-Pilly TROP est un ouvrage d’infectiologie tropicale destiné aux médecins et aux étudiants en médecine des pays francophones du Sud. La prise en compte des différents niveaux de la pyramide sanitaire dans ces pays le rend aussi accessible aux infirmiers des centres de santé communautaires urbains et des structures de santé intermédiaires des zones rurales. Par définition, les Pays En Développement accroissant progressivement leurs capacités de diagnostic biologique et de traitement, les outils de prise en charge correspondent aux moyens des niveaux périphériques comme à ceux des niveaux hospitaliers de référence

    Involvement of the Efflux Pumps in Chloramphenicol Selected Strains of Burkholderia thailandensis: Proteomic and Mechanistic Evidence

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    Burkholderia is a bacterial genus comprising several pathogenic species, including two species highly pathogenic for humans, B. pseudomallei and B. mallei. B. thailandensis is a weakly pathogenic species closely related to both B. pseudomallei and B. mallei. It is used as a study model. These bacteria are able to exhibit multiple resistance mechanisms towards various families of antibiotics. By sequentially plating B. thailandensis wild type strains on chloramphenicol we obtained several resistant variants. This chloramphenicol-induced resistance was associated with resistance against structurally unrelated antibiotics including quinolones and tetracyclines. We functionally and proteomically demonstrate that this multidrug resistance phenotype, identified in chloramphenicol-resistant variants, is associated with the overexpression of two different efflux pumps. These efflux pumps are able to expel antibiotics from several families, including chloramphenicol, quinolones, tetracyclines, trimethoprim and some β-lactams, and present a partial susceptibility to efflux pump inhibitors. It is thus possible that Burkholderia species can develop such adaptive resistance mechanisms in response to antibiotic pressure resulting in emergence of multidrug resistant strains. Antibiotics known to easily induce overexpression of these efflux pumps should be used with discernment in the treatment of Burkholderia infections

    Identification and Evolution of Drug Efflux Pump in Clinical Enterobacter aerogenes Strains Isolated in 1995 and 2003

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    BACKGROUND: The high mortality impact of infectious diseases will increase due to accelerated evolution of antibiotic resistance in important human pathogens. Development of antibiotic resistance is a evolutionary process inducing the erosion of the effectiveness of our arsenal of antibiotics. Resistance is not necessarily limited to a single class of antibacterial agents but may affect many unrelated compounds; this is termed 'multidrug resistance' (MDR). The major mechanism of MDR is the active expulsion of drugs by bacterial pumps; the treatment of gram negative bacterial infections is compromised due to resistance mechanisms including the expression of efflux pumps that actively expel various usual antibiotics (beta-lactams, quinolones, ...). METHODOLOGY/PRINCIPAL FINDINGS: Enterobacter aerogenes has emerged among Enterobacteriaceae associated hospital infections during the last twenty years due to its faculty of adaptation to antibiotic stresses. Clinical isolates of E. aerogenes belonging to two strain collections isolated in 1995 and 2003 respectively, were screened to assess the involvement of efflux pumps in antibiotic resistance. Drug susceptibility assays were performed on all bacterial isolates and an efflux pump inhibitor (PAbetaN) previously characterized allowed to decipher the role of efflux in the resistance. Accumulation of labelled chloramphenicol was monitored in the presence of an energy poison to determine the involvement of active efflux on the antibiotic intracellular concentrations. The presence of the PAbetaN-susceptible efflux system was also identified in resistant E. aerogenes strains. CONCLUSIONS/SIGNIFICANCE: For the first time a noticeable increase in clinical isolates containing an efflux mechanism susceptible to pump inhibitor is report within an 8 year period. After the emergence of extended spectrum beta-lactamases in E. aerogenes and the recent characterisation of porin mutations in clinical isolates, this study describing an increase in inhibitor-susceptible efflux throws light on a new step in the evolution of mechanism in E. aerogenes

    ICP Monitoring and Phase-Contrast MRI to Investigate Intracranial Compliance

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    16th International Conference on Intracranial Pressure and Neuromonitoring (ICP), Cambridge, MA, JUN 28-JUL 02, 2016International audienceObjective: The amplitude of intracranial pressure (ICP) can be measured by ICP monitoring. Phase-contrast magnetic resonance imaging (PCMRI) can quantify blood and cerebrospinal fluid (CSF) flows. The aim of this work was to investigate intracranial compliance at rest by combining baseline ICP monitoring and PCMRI in hydrocephalus patients. Materials and methods: ICP monitoring was performed before infusion testing to quantify Delta ICP_rest at the basal condition in 33 suspected hydrocephalus patients (74 years). The day before, patients had had a PCMRI to assess total cerebral blood flow (tCBF), intracranial blood volume change (stroke volume SVblood), and cervical CSF volume change (the stroke volume CSV). Global (blood and CSF) intracranial volume change (Delta IVC) during each cardiac cycle (CC) was calculated. Finally, Compliance: C_rest = Delta IVC/Delta ICP_rest was calculated. The data set was postprocessed by two operators according to blind analysis. Results: Bland-Altman plots showed that measurements presented no significant difference between the two operators. Delta ICP_rest = 2.41 +/- 1.21 mmHg, tCBF = 469.89 +/- 127.54 mL/min, SVblood = 0.82 +/- 0.32 mL/cc, CSV = 0.50 +/- 0.22 mL/cc, Delta IVC = 0.44 +/- 0.22 mL, and C_rest = 0.23 +/- 0.15 mL/mmHg. There are significant relations between SVblood and CSV and also SVblood and tCBF. Conclusions: During ``basal'' condition, the compliance amplitude of the intracranial compartment is heterogeneous in suspected hydrocephalus patients, and its value is lower than expected! This new parameter could represent new information, complementary to conventional infusion tests. We hope that this information can be applied to improve the selection of patients for shunt surgery

    Membrane permeability and regulation of drug "influx and efflux" in enterobacterial pathogens.

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    In Enterobacteriaceae, membrane permeability is a key in the level of susceptibility to antibiotics. Modification of the bacterial envelope by decreasing the porin production or increasing the expression of efflux pump systems has been reported. These phenomena are frequently associated with other resistance mechanisms such as alteration of antibiotics or modification of the drug targets, in various clinical isolates showing a Multi Drug Resistant phenotype (MDR). In Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae and Salmonella enterica several genes and external factors are involved in the emergence of MDR isolates. These bacterial isolates exhibit a noticeable reduction of functional porins per cell due to a decrease, a complete shutdown of synthesis, or the expression of an altered porin and a high expression of efflux systems (e.g. overexpression of the pump). The combined action of these mechanisms during an infection confers a significant decrease in bacterial sensitivity to antibiotherapy ensuring dissemination and colonization of the patient and favours the acquisition of additional mechanisms of resistance. MarA and ramA are involved in a complex regulation cascade controlling membrane permeability and actively participate in the triggering of the MDR phenotype. Mutations in regulator genes have been shown to induce the overproduction of efflux and the down-regulation of porin synthesis. In addition, various compounds such as salicylate, imipenem or chloramphenicol are able to activate the MDR response. This phenomenon has been observed both in vitro during culture of bacteria in the presence of drugs and in vivo during antibiotic treatment of infected patients. These effectors activate the expression of specific global regulators, marA, ramA, or target other genes located downstream in the regulation cascade
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