How predictable is development of resistance after β-lactam therapy in Enterobacter cloacae infection?

Certain non-fastidious Gram-negative bacilli, notably Enterobacter cloacae, although classified as susceptible by usual in-vitro susceptibility testing, often become resistant in patients treated with newer β-lactam antibiotics. Here various in-vitro tests were carried out together with an animal model allowing the quantification of resistance that emerges after short term therapy. Mice were challenged (102 cfu plus talcum) intraperitoneally with one each of four strains of Ent. cloacae. Two hours later, a single β-lactam dose was administered subcutaneously. The following day, the peritoneal bacterial population was analysed by using antibiotic-containing gradient plates. Development of resistance after therapy varied according to the compound considered. Imipenem (50 mg/kg) produced no resistance, and piperacillin (200 mg/kg) only a few, while resistance occurred frequently after therapy with aztreonam (50 mg/kg), ceftazidime (50 mg/kg), cefotaxime (50 mg/kg) and cefpirome (50 mg/kg). MICs increased by at least 16-fold when resistance developed. No simple correlations were found between these in-vivo results and initial MICs, killing kinetics, frequency of resistant variants within the bacterial populations before therapy, initial MIC of these variants or antibiotic concentrations assayed in peritoneal fluid 60 min after dosing. The most reliable predictive in-vitro test appeared to be the determination of resistance emerging in broth containing at least 16 times the MIC of the antibiotic tested. Such a test is unlikely to be used on a routine basis. When a β-lactam compound seems appropriate for treating an Enterobacter infection, it may be advisable to avoid drugs that are prone prone to produce resistance in experimental or clinical infections, whatever the results of conventional in-vitro susceptibility test

Emergence of resistance after therapy with antibiotics used alone or combined in a marine model

A murine model of peritonitis allowing detection and quantification of in-vivo acquired resistance during short term therapy has been used in order to evaluate the capacity of antimicrobial combinations to limit emergence of resistance, as compared to individual components of the regimens. Mice were challenged intraperitoneally with 108 cfu of bacteria. Two hours later, a single antibiotic dose was injected subcutaneously: amikacin (15 mg/kg), ceftriaxone (50 mg/kg), pefloxacin (25 mg/kg), amikacin + ceftriaxone, amikacin + pefloxacin or ceftriaxone + pefloxacin. Escherichia coli and Staphylococcus aureus never became resistant. Single drug therapy yielded resistant mutants in Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae and Pseudomonas aeruginosa as follows: 74% of ceftriaxone-treated animals, 57% of pefloxacin treated animals and 27% of amikacin treated animals. All the tested combinations reduced the frequency of in-vivo acquired resistance produced by single drugs, and no combination selected resistance when the separate agents of the combination did not. Combining antimicrobial agents limits the risk of emergence of resistance during antibiotic therap

In-vitro activity of newer quinolones against aerobic bacteria

Nalidixic and five newer 4-quinolones, ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin were tested against 576 recent clinical aerobic bacterial isolates. The 4-quinolones were regularly active (MIC90 < 4 mg/1) against the following bacteria: Staphylococcus aureus, S. epidermidis, S. saprophyticus, different Enterobacteriaceae, Haemophilus influenzae, Campylobacter jejuni, Pseudomonas aeruginosa, Agrobacter spp., Aeromonas spp., Plesiomonas spp., Neisseria meningitidis. Other bacteria were usually intermediately susceptible or resistant: different streptococci, Listeria monocytogenes, Nocardia asteroides, P. maltophilia, Achromobacter xylosoxydans and Alcaligenes denitrificans. Ciprofloxacin was the most potent compound, followed by ofloxacin and pefloxacin, norfloxacin and enoxacin being less active. All the 4-quinolones were much more active than nalidixic acid. The MBC/MIC ratios of the 4-quinolones were between 1 and 2 with a majority of strains, and between 2 and 3 with Streptococcus agalactiae, Str. faecalis and L. monocytogenes. A two- to eight-fold increase of MIC was observed by increasing the inoculum 10,000-fold with most of the strains tested. Susceptible bacterial population of Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and P. aeruginosa contained more clones resistant to nalidixic acid (104 to 108 at four times the MIC) than to 4-quinolones (105 to 109 at four times the MIC). Supplementing the media with MgSO4 produced smaller inhibition zone diameters with a disc diffusion method than those obtained with non-supplemented agar, with all quinolone or strains. Less regular effect, or no effect was obtained after supplementation with ZnSO4 or Ca(NO3)

Pour en finir avec le XXIe siècle

Culture of Narcissism: American Life in An Age of Diminishing Expectations a été publié aux États-Unis en 1979. Christopher Lasch (1932–1994) qui avait déjà écrit plusieurs ouvrages de sociologie, en particulier de la famille (Haven in a Heartless World : The Family Besieged, 1977), y fait un portrait psycho-social d’une société américaine absorbée dans la contemplation et l’adoration de sa propre image, construite en particulier par les sciences sociales. Ce livre militant suscita à l’époque nombre de controverses et popularisa le terme « national malaise », version post-freudienne du malaise dans la civilisation. Une traduction française a paru en 1981 chez Robert Laffont dans la collection Libertés 2000 dirigée par Georges Liébert et Emmanuel Todd, sous le titre du Complexe de Narcisse. Cette traduction, devenue rapidement introuvable, a été republiée en 2001, augmentée d’une postface inédite de l’auteur, par les éditions Climats. Nous avons choisi de proposer dans TransatlanticA la préface originale à cette édition, rédigée par le philosophe Jean-Claude Michéa. Sa lecture engagée de Lasch nous a paru propre à susciter débats et réactions autour d’une oeuvre foisonnante, polémique et parfois datée aussi. Nous encourageons les lecteurs à poursuivre l’échange en nous écrivant. Nous publierons les principaux commentaires dans le numéro 3 de TransatlanticA

Pour en finir avec le XXIe siècle

Culture of Narcissism: American Life in An Age of Diminishing Expectations a été publié aux États-Unis en 1979. Christopher Lasch (1932–1994) qui avait déjà écrit plusieurs ouvrages de sociologie, en particulier de la famille (Haven in a Heartless World : The Family Besieged, 1977), y fait un portrait psycho-social d’une société américaine absorbée dans la contemplation et l’adoration de sa propre image, construite en particulier par les sciences sociales. Ce livre militant suscita à l’époque nombre de controverses et popularisa le terme « national malaise », version post-freudienne du malaise dans la civilisation. Une traduction française a paru en 1981 chez Robert Laffont dans la collection Libertés 2000 dirigée par Georges Liébert et Emmanuel Todd, sous le titre du Complexe de Narcisse. Cette traduction, devenue rapidement introuvable, a été republiée en 2001, augmentée d’une postface inédite de l’auteur, par les éditions Climats. Nous avons choisi de proposer dans TransatlanticA la préface originale à cette édition, rédigée par le philosophe Jean-Claude Michéa. Sa lecture engagée de Lasch nous a paru propre à susciter débats et réactions autour d’une oeuvre foisonnante, polémique et parfois datée aussi. Nous encourageons les lecteurs à poursuivre l’échange en nous écrivant. Nous publierons les principaux commentaires dans le numéro 3 de TransatlanticA

Accelerating a 3D finite-difference wave propagation code using GPU graphics cards

International audienceWe accelerate a three-dimensional finite-difference in the time domain (FDTD) wave propagation code by a factor between about 20 and 60 compared to a serial implementation using Graphics Processing Unit (GPU) computing on NVIDIA graphics cards with the CUDA programming language. We describe the implementation of the code in CUDA to simulate the propagation of seismic waves in a heterogeneous elastic medium. We also implement Convolution Perfectly Matched Layers (CPMLs) on the graphics cards to efficiently absorb outgoing waves on the fictitious edges of the grid. We show that the code that runs on a graphics card gives the expected results by comparing our results to those obtained by running the same simulation on a classical processor core. The methodology that we present can be used for Maxwell's equations as well because their form is similar to that of the seismic wave equation written in velocity vector and stress tensor

NLSEmagic: Nonlinear Schr\"odinger Equation Multidimensional Matlab-based GPU-accelerated Integrators using Compact High-order Schemes

We present a simple to use, yet powerful code package called NLSEmagic to numerically integrate the nonlinear Schr\"odinger equation in one, two, and three dimensions. NLSEmagic is a high-order finite-difference code package which utilizes graphic processing unit (GPU) parallel architectures. The codes running on the GPU are many times faster than their serial counterparts, and are much cheaper to run than on standard parallel clusters. The codes are developed with usability and portability in mind, and therefore are written to interface with MATLAB utilizing custom GPU-enabled C codes with the MEX-compiler interface. The packages are freely distributed, including user manuals and set-up files.Comment: 37 pages, 13 figure

Hybrid Multicore/vectorisation technique applied to the elastic wave equation on a staggered grid

In modern physics it has become common to find the solution of a problem by solving numerically a set of PDEs. Whether solving them on a finite difference grid or by a finite element approach, the main calculations are often applied to a stencil structure. In the last decade it has become usual to work with so called big data problems where calculations are very heavy and accelerators and modern architectures are widely used. Although CPU and GPU clusters are often used to solve such problems, parallelisation of any calculation ideally starts from a single processor optimisation. Unfortunately, it is impossible to vectorise a stencil structured loop with high level instructions. In this paper we suggest a new approach to rearranging the data structure which makes it possible to apply high level vectorisation instructions to a stencil loop and which results in significant acceleration. The suggested method allows further acceleration if shared memory APIs are used. We show the effectiveness of the method by applying it to an elastic wave propagation problem on a finite difference grid. We have chosen Intel architecture for the test problem and OpenMP (Open Multi-Processing) since they are extensively used in many applications

Collaborative simulation and scientific big data analysis: Illustration for sustainability in natural hazards management and chemical process engineering

Classical approaches for remote visualization and collaboration used in Computer-Aided Design and Engineering (CAD/E) applications are no longer appropriate due to the increasing amount of data generated, especially using standard networks. We introduce a lightweight and computing platform for scientific simulation, collaboration in engineering, 3D visualization and big data management. This ICT based platform provides scientists an “easy-to-integrate” generic tool, thus enabling worldwide collaboration and remote processing for any kind of data. The service-oriented architecture is based on the cloud computing paradigm and relies on standard internet technologies to be efficient on a large panel of networks and clients. In this paper, we discuss the need of innovations in (i) pre and post processing visualization services, (ii) 3D large scientific data set scalable compression and transmission methods, (iii) collaborative virtual environments, and (iv) collaboration in multi-domains of CAD/E. We propose our open platform for collaborative simulation and scientific big data analysis. This platform is now available as an open project with all core components licensed under LGPL V2.1. We provide two examples of usage of the platform in CAD/E for sustainability engineering from one academic application and one industrial case study. Firstly, we consider chemical process engineering showing the development of a domain specific service. With the rise of global warming issues and with growing importance granted to sustainable development, chemical process engineering has turned to think more and more environmentally. Indeed, the chemical engineer has now taken into account not only the engineering and economic criteria of the process, but also its environmental and social performances. Secondly, an example of natural hazards management illustrates the efficiency of our approach for remote collaboration that involves big data exchange and analysis between distant locations. Finally we underline the platform benefits and we open our platform through next activities in innovation techniques and inventive design

High-frequency simulations of global seismic wave propagation using SPECFEM3D_GLOBE on 62K processors

SPECFEM3D_GLOBE is a spectral element application enabling the simulation of global seismic wave propagation in 3D anelastic, anisotropic, rotating and self-gravitating Earth models at unprecedented resolution. A fundamental challenge in global seismology is to model the propagation of waves with periods between 1 and 2 seconds, the highest frequency signals that can propagate clear across the Earth. These waves help reveal the 3D structure of the Earth's deep interior and can be compared to seismographic recordings. We broke the 2 second barrier using the 62K processor Ranger system at TACC. Indeed we broke the barrier using just half of Ranger, by reaching a period of 1.84 seconds with sustained 28.7 Tflops on 32K processors. We obtained similar results on the XT4 Franklin system at NERSC and the XT4 Kraken system at University of Tennessee Knoxville, while a similar run on the 28K processor Jaguar system at ORNL, which has better memory bandwidth per processor, sustained 35.7 Tflops (a higher flops rate) with a 1.94 shortest period. Thus we have enabled a powerful new tool for seismic wave simulation, one that operates in the same frequency regimes as nature; in seismology there is no need to pursue periods much smaller because higher frequency signals do not propagate across the entire globe. We employed performance modeling methods to identify performance bottlenecks and worked through issues of parallel I/O and scalability. Improved mesh design and numbering results in excellent load balancing and few cache misses. The primary achievements are not just the scalability and high teraflops number, but a historic step towards understanding the physics and chemistry of the Earth's interior at unprecedented resolution