Evaluation of a new rapid immunochromatographic assay for the detection of GES-producing Gram-negative bacteria

International audienceAbstract Background As carbapenemase-producing Enterobacterales are increasingly reported worldwide, their rapid detection is crucial to reduce their spread and prevent infections and outbreaks. Lateral flow immunoassays (LFIAs) have become major tools for the detection of carbapenemases. However, as for most commercially available assays, only the five main carbapenemases are targeted. Objectives Here, we have developed and evaluated an LFIA prototype for the rapid and reliable detection of the increasingly identified GES-type β-lactamases. Methods The GES LFIA was validated on 103 well-characterized Gram-negative isolates expressing various β-lactamases grown on Mueller–Hinton (MH) agar, chromogenic, and chromogenic/selective media. Results The limit of detection of the assay was 106 cfu per test with bacteria grown on MH agar plates. GES LFIA accurately detected GES-type β-lactamases irrespective of the culture media and the bacterial host. The GES LFIA was not able to distinguish between GES-ESBLs and GES-carbapenemases. Because GES enzymes are still rare, their detection as an ESBL or a carbapenemase remains important, especially because extensive use of carbapenems to treat ESBL infections may select for GES variants capable of hydrolysing carbapenems. Conclusions The GES LFIA is efficient, rapid and easy to implement in the routine workflow of a clinical microbiology laboratory for the confirmation of GES-type β-lactamases. Combining it with immunochromatographic assays targeting the five main carbapenemases (KPC, NDM, VIM, IMP and OXA-48) would improve the overall sensitivity for the most frequently encountered carbapenemases and ESBLs, especially in non-fermenters

A Lateral Flow Immunoassay for the Rapid Identification of CTX-M-Producing Enterobacterales from Culture Plates and Positive Blood Cultures

International audienceWe have developed a lateral flow immunoassay (LFIA), named NG-Test CTX-M MULTI (NG-Test), to detect group 1, 2, 8, 9, 25 CTX-M producers from agar plates and from positive blood cultures in less than 15 min. The NG-Test was validated retrospectively on 113 well-characterized enterobacterial isolates, prospectively on 102 consecutively isolated ESBL-producers from the Bicêtre hospital and on 100 consecutive blood cultures positive with a gram-negative bacilli (GNB). The NG-Test was able to detect all CTX-M producers grown on the different agar plates used in clinical microbiology laboratories. No false positive nor negative results were observed. Among the 102 consecutive ESBL isolates, three hyper mucous isolates showed an incorrect migration leading to invalid results (no control band). Using an adapted protocol, the results could be validated. The NG-Test detected 99/102 ESBLs as being CTX-Ms. Three SHV producers were not detected. Among the 100 positive blood cultures with GNB tested 10/11 ESBL-producers were detected (8 CTX-M-15, 2 CTX-M-27). One SHV-2-producing-E. cloacae was missed. The NG-Test CTX-M MULTI showed 100% sensitivity and specificity with isolates cultured on agar plates and was able to detect 98% of the ESBL-producers identified in our clinical setting either from colonies or from positive blood cultures

Arbitrage et conciliation dans l'Islam médiéval et moderne

La justice en Islam est souvent associée au personnage du cadi, juge nommé par le pouvoir. L’État n’eut cependant jamais le monopole de la résolution des conflits. L’arbitre et le médiateur proposaient deux alternatives possibles, fondées sur le consensus des parties. Tandis que le premier, doté d’un rôle décisionnel, pouvait rendre une sentence généralement considérée comme exécutoire, le second orchestrait un processus de négociation se concluant par un accord à l’amiable. Face à des modes d’adjudication visant à déterminer un vainqueur et un perdant, la conciliation était tenue en haute estime par les juristes comme par les justiciables. La recherche d’un moyen terme permettait non seulement à chacun des adversaires de garder la face, mais servait aussi à préserver l’apparence d’une communauté musulmane unie. Les dix contributions à ce dossier thématique explorent le fonctionnement de l’arbitrage et de la conciliation dans divers contextes, maghrébins et moyen-orientaux, depuis l’apparition de l’Islam jusqu’à la fin du xviiie siècle. Dans le cadre de litiges aux fondements juridiques, ces deux procédés pouvaient soit offrir une alternative à la justice du pouvoir, soit s’y articuler pour assouplir la prise de décision et l’adapter aux réalités sociales. Au-delà de cette complexe articulation entre institutions judiciaires officielles et privées, la conciliation fut aussi un outil essentiel de gestion des rivalités politiques, tout particulièrement dans le milieu de la cour. L’image idéale de consensus associée aux procédures de conciliation ne doit cependant pas occulter des stratégies peu avouables par les acteurs eux-mêmes. C’est que la transaction permettait, aussi, de contourner la loi islamique, parfois au détriment de l’équité. Cette livraison de la Remmm invite ainsi à une lecture dynamique des conflits et de leurs résolutions en rapport avec leurs contextes historiques

The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up

Accurate prediction of progression in subjects at risk of Alzheimer's disease is crucial for enrolling the right subjects in clinical trials. However, a prospective comparison of state-of-the-art algorithms for predicting disease onset and progression is currently lacking. We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of patient-specific biomarkers. On a limited, cross-sectional subset of the data emulating clinical trials, performance of the best algorithms at predicting clinical diagnosis decreased only slightly (2 percentage points) compared to the full longitudinal dataset. The submission system remains open via the website https://tadpole.grand-challenge.org, while TADPOLE SHARE (https://tadpole-share.github.io/) collates code for submissions. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.</jats:p