Ceftazidime/avibactam alone or in combination with aztreonam against colistin-resistant and carbapenemase-producing Klebsiella pneumoniae

The spread of carbapenemase-producing Klebsiella pneumoniae is a major public health concern since such isolates are basically resistant to most available antibiotics, including β-lactams, fluoroquinolones and aminoglycosides.1 Infections due to carbapenemase-producing K. pneumoniae are therefore commonly treated with a regimen containing colistin.1 However, acquired resistance to colistin now occurs frequently and has few therapeutic options.2 Outbreaks with colistin-resistant and carbapenemase-producing K. pneumoniae isolates have been reported worldwide2 and mortality rates are high owing to limited treatment options.3...Recently, a new therapeutic option, namely ceftazidime/avibactam, combining a broad-spectrum cephalosporin and a novel β-lactamase inhibitor, has been marketed. The addition of avibactam expands the spectrum of activity of ceftazidime to many MDR Enterobacteriaceae including producers of ESBLs and carbapenemases.4..

Les exercices grammaticaux dans le cadre de l’enseignement rénové du français: usages, problèmes, perspectives

Cet article est centré sur les exercices grammaticaux à l’école primaire. Il en analyse d’abord les caractéristiques, en prenant comme critère dominant les actions attendues de la part des élèves. Il en discute ensuite la pertinence, en prenant comme repères les principes et les démarches de l’enseignement rénové du français ainsi que les objectifs de l’enseignement grammatical. Enfin, il énonce quelques pistes de réflexion et d’action pour la pratique de classe et pour la formation des enseignants en ce domaine.This article focuses on grammar exercises in primary schools. Firstly, it analyses the characteristics of the exercises, taking as its main criterion the actions expected from the pupils. It also discusses their relevance, taking as a reference point the principles and approaches associated with French teaching reforms as well as the objectives of teaching grammar. Finally, it sets out some ideas for action and reflection on classroom practice and for teacher training in this field

Comparison of methods for detection of plasmid-mediated and chromosomally encoded colistin resistance in Enterobacteriaceae

Objectives: Because of the emergence of plasmid-mediated (mcr-1 and mcr-2 genes) and chromosomally encoded colistin resistance, reliable methods for detecting colistin resistance/susceptibility in routine laboratories are required. We evaluated the respective performances of the BD Phoenix automated system, the newly developed Rapid Polymyxin NP test and the broth microdilution (BMD) reference method to detect colistin resistance in Enterobacteriaceae, and particularly those producing mcr-1 and mcr-2.Methods: Colistin susceptibility of 123 enterobacterial clinical isolates (40 colistin-susceptible and 83 colistin-resistant isolates) was tested with the BD Phoenix automated system, the Rapid Polymyxin NP test and the BMD method. Molecular mechanisms responsible for plasmid-mediated and chromosomally encoded colistin resistance mechanisms were investigated by PCR and sequencing.Results: Considering BMD as a reference method, the BD Phoenix system failed to detect ten colistin-resistant isolates (one Escherichia coli, one Klebsiella pneumoniae, seven Enterobacter species and one Salmonella enterica). The Rapid Polymyxin NP test failed to detect the same single E. coli isolate. Those two latter methods detected the 16 E. coli, K. pneumoniae and S. enterica isolates producing the plasmid-encoded mcr-1 and mcr-2.Conclusions: The BD Phoenix system and the Rapid Polymyxin NP test are reliable techniques for detecting plasmid-mediated mcr-1 and mcr-2-related colistin resistance. However, a high rate of false susceptibility was observed with the BD Phoenix system, indicating that susceptibility results obtained with that system should be confirmed by BMD method. By contrast, the Rapid Polymyxin NP test showed a good agreement with the BMD method, and results were obtained rapidly (within 2 hours). The BMD method should be performed if minimum inhibitory concentration values are neede

Evaluation of three broth microdilution systems to determine colistin susceptibility of Gram-negative bacilli

The broth microdilution (BMD) method is currently the recommended technique to determine susceptibility to colistin.Objectives: We evaluated the accuracy of three commercialized BMD panels [Sensititre (ThermoFisher Diagnostics), UMIC (Biocentric) and MicroScan (Beckman Coulter)] to determine colistin susceptibility.Methods: A collection of 185 isolates of Gram-negative bacilli (133 colistin resistant and 52 colistin susceptible) was tested. Manual BMD according to EUCAST guidelines was used as the reference method, and EUCAST 2017 breakpoints were used for susceptibility categorization.Results:The UMIC system gave the highest rate of very major errors (11.3%) compared with the Sensititre and MicroScan systems (3% and 0.8%, respectively). A high rate of major errors (26.9%) was found with the MicroScan system due to an overestimation of the MICs for the non-fermenting Gram-negative bacilli, whereas no major errors were found with the Sensititre and UMIC systems.Conclusions: The UMIC system was easy to use, but failed to detect >10% of colistin-resistant isolates. The MicroScan system showed excellent results for enterobacterial isolates, but non-susceptible results for non- fermenters should be confirmed by another method and the range of MICs tested was narrow. The Sensititre system was the most reliable marketed BMD panel with a categorical agreement of 97.8%

Charcoal kilns and environmental history in the eastern Pyrenees (France). A methodological approach

International audienceSince 15 years, an interdisciplinary research program on long-term forest history and the impact of metallurgy has been undertaken in the eastern Pyrenees. The objective is to describe the spatial evolution of forests and pastoral landscapes and the principal historical events and their causes. Our methodology is based on large-scale regressive studies of various characteristic sites (in valleys or forests) and includes the application of history, phytogeography, palynology, anthropology and archaeology. Remains of charcoal kilns are numerous in the mouton forest areas, wether these are actual or potential, all over the eastern Pyrenees and in particular in Ariege and in the Catalan mountains. Charcoal kilns can thus be used as tool for reconstructing environmental history and ancient woodlands. Two different methods are described here : (i) an anthraco-biogeographic method, based on a geosystemic approach, comparative studies and spatialisation of results ; (ii) an archeo-environmental method, that allows a precise diachronic study of limited forest units and charcoal kilns sites.Un programme interdisciplinaire de recherche est conduit depuis 15 ans sur l'histoire des forêts et l'impact de la métallurgie au bois dans les Pyrénées de l'est. L'objectif est de décrire l'évolution spatiale des paysages forestiers et pastoraux et de saisir les principaux seuils historiques et leurs causes. La méthodologie est basée sur l'étude régressive à grande échelle de sites caractéristiques (vallée ou unités forestières), en utilisant la phytogéographie, la palynologie, l'anthracologie et l'archéologie. Dans toutes les Pyrénées de l'est, en particulier dans les montagnes ariégeoises et catalanes, les restes d'anciennes charbonnières sont innombrables dans l'ensemble de l'aire de la forêt, actuelle ou potentielle. Les charbonnières ont donc été utilisées en tant qu'outil pour l'histoire de l'environnement et la reconstitution des forêts du passé. Deux méthodes sont décrites ici : (i) la méthode anthraco-biogéographique qui est basée sur une démarche géosystémique et permet une approche comparative et spatialité ; (ii) la méthode archéo-environnementale qui permet une étude diachronique précise d'unités forestières limitées et des sites de charbonnage

Hafnia, an enterobacterial genus naturally resistant to colistin revealed by three susceptibility testing methods

ObjectivesTo determine the susceptibility to colistin of Hafnia alvei and Hafnia paralvei, and to compare methods for colistin resistance detection in the Hafnia genus.MethodsA collection of 25 Hafnia isolates was studied. Species were identified by using 16S rRNA gene sequencing with subsequent phylogeny analysis. Susceptibility to colistin was determined using the broth microdilution (BMD) reference method, the Phoenix automated system, the Rapid Polymyxin NP test, the Etest system and the disc diffusion method.ResultsThe collection consisted of 15 H. alvei and 10 H. paralvei isolates. Based on the 16S rRNA analysis, a close relationship of the Hafnia genus with naturally colistin-resistant enterobacterial genera (Proteus, Morganella, Providencia and Serratia) was identified. Susceptibility testing performed using the BMD method, the Phoenix automated system and the Rapid Polymyxin NP test revealed a high rate of colistin resistance (96%). Underestimation of colistin resistance using Etest strips (72%) and the disc diffusion method (0%) was observed.ConclusionsThe high rate of colistin resistance observed within the Hafnia genus and its close phylogenetic relationship with naturally colistin-resistant genera suggest that Hafnia is a naturally colistin-resistant enterobacterial genus

Histoire de l'environnement et cartographie du temps dans la moitié est des Pyrénées. Pour une " chrono-chorologie ".

Des recherches interdisciplinaires ont été menées à partir de la fin des années 1980 dans les Pyrénées. Elles portent sur une période allant du Néolithique à l'actuel. Un des objectifs de ces travaux était d'obtenir une représentation spatiale des états successifs de l'environnement sous forme de modèles paysagers ou de cartographies éco-historiques. Ces représentations spatiales sont issues du croisement de relevés phytogéographiques et de données historiques, archéologiques, paléo-environnementales. Elles ont été facilitées par l'impact ancien de la métallurgie au bois et du charbonnage dans toute la moitié orientale des Pyrénées. En effet, la multitude de vestiges que ces pratiques ont laissé dans tout l'espace étudié (charbonnières, crassiers de forges, mines) permet une spatialisation des modes d'exploitation passés, et une analyse comparative entre sources historiques et paléo-environnementales. Est présentée ici une synthèse chronologique de l'évolution des espaces forestiers à l'échelle des Pyrénées de l'est, sous la forme de chrono-systèmes. Ces chrono-systèmes font ensuite l'objet d'une tentative de cartographie sous forme d'états successifs de l'environnement à l'échelle 1/250 000ème

Endogenous Plasma Peptide Detection and Identification in the Rat by a Combination of Fractionation Methods and Mass Spectrometry

Mass spectrometry-based analyses are essential tools in the field of biomarker research. However, detection and characterization of plasma low abundance and/or low molecular weight peptides is challenged by the presence of highly abundant proteins, salts and lipids. Numerous strategies have already been tested to reduce the complexity of plasma samples. The aim of this study was to enrich the low molecular weight fraction of rat plasma. To this end, we developed and compared simple protocols based on membrane filtration, solid phase extraction, and a combination of both. As assessed by UV absorbance, an albumin depletion >99% was obtained. The multistep fractionation strategy (including reverse phase HPLC) allowed detection, in a reproducible manner (CV < 30%–35%), of more than 450 peaks below 3000 Da by MALDI-TOF/MS. A MALDI-TOF/MS-determined LOD as low as 1 fmol/μL was obtained, thus allowing nanoLC-Chip/MS/MS identification of spiked peptides representing ~10−6% of total proteins, by weight. Signal peptide recovery ranged between 5%–100% according to the spiked peptide considered. Tens of peptide sequence tags from endogenous plasma peptides were also obtained and high confidence identifications of low abundance fibrinopeptide A and B are reported here to show the efficiency of the protocol. It is concluded that the fractionation protocol presented would be of particular interest for future differential (high throughput) analyses of the plasma low molecular weight fraction

A reuse-Oriented Approach for the Construction of Scenario Bases Methods

International audienceDespite the recent interest in scenarios, the development of new methods and tools for Requirements Engineering integrating scenario based approaches has been limited. This paper reports on four different processes developed from research undertaken as part of the CREWS project which the authors believe will improve scenario use and make it more systematic. Furthermore CREWS aims to integrate these approaches into a method for scenario-based requirements engineering. To achieve this objective and be able to include existing approaches such as use case analysis we develop a component based approach which reflects a shift towards a reuse-centric approach to method engineering. The paper presents CREWS method and meta-method knowledge through the implementation of an SGML database to store, retrieve and dynamically compose chunks of CREWS processes