Extended-spectrum β-lactamase, carbapenemase, and the mcr-1 gene: Is there a historical link?

The plasmid mediated mcr-1 gene encoding for Enterobacteriaceae colistin resistance has been recently identified across five continents. The objective of the present study was to trace historical events concerning the discovery and emergence of the mcr-1 gene along with ESBL and carbapenemase genes since several studies have reported identifying mcr-1 genes among Extended-Spectrum β-Lactamases (ESBL) and/or carbapenemase producing Escherichia coli. A retrospective study reported the identification of the mcr-1 gene in E. coli strains isolated in the 1980s, and this seems to correspond to the first identification of ESBL enzymes. The first discovery of the New Delhi metallo-beta-lactamase-1 (NDM-1) in 2009 was associated with a significant increase in mcr-1 gene prevalence in E. coli strains obtained from food producing animals. We noticed that a historical link has existed between mcr-1, ESBL and carbapenemase genes since the 1980s, and we believe that the re-evaluation of colistin use in livestock needs an overall approach that includes not only colistin use reduction but also the reduction of all antibiotic use

Effet d’une supplémentation en vitamine E alimentaire sur l’inflammation et la douleur chez le chien avec arthrose

La vitamine E (VE) est parfois préconisée pour le traitement de l’arthrose chez le chien, par contre aucune étude n’a documenté cette efficacité. L’objectif de cette étude était de déterminer l’effet d’une forte dose de VE alimentaire sur l’inflammation et la douleur arthrosique chez le chien. Deux groupes de chiens avec arthrose provoquée par section du ligament croisé crânial du membre postérieur droit ; un groupe contrôle (n=8) et un groupe supplémenté avec la VE (n=7), ont été suivis selon un design parallèle, randomisé et en aveugle. La supplémentation a été commencée 1 jour après la chirurgie avec une dose de 400 UI/animal/jour par voie orale pendant 56 jours. Les évaluations objectives (activité électrodermique, EDA) et subjectives (VAS, NRS) de la douleur ont été faites avant la chirurgie J0, à J28 et à J55 après chirurgie. La détermination de la concentration synoviale des marqueurs de l’inflammation (IL-1β, PGE2 et NOx) et l’étude lésionnelle ont été faites après l’euthanasie à J56. Une comparaison unilatérale avec un seuil alpha de 10% a été réalisée. Les concentrations synoviales de PGE2 et de NOx étaient faibles chez le groupe supplémenté en VE par rapport au contrôle (P=0,03 et P<0,0001 respectivement). Les valeurs de VAS, NRS et EDA ont montré une tendance constante à l’amélioration de la douleur dans le groupe traité, avec des résultats significatifs obtenus pour VAS à J55 et pour EDA à J28 (P ajusté = 0,07 dans les deux cas). L’analyse histologique du cartilage articulaire a montré une réduction significative des scores lésionnels dans le groupe traité. C’est la première fois qu’une étude menée chez le chien avec arthrose, a montré qu’une forte dose en VE alimentaire permet de réduire les marqueurs de l’inflammation articulaire, les lésions histologiques cartilagineuses et permet aussi d’améliorer les signes de la douleur associe à l’arthrose.Because of the evidence of some anti-inflammatory and analgesic activities of vitamin E (VE) in human osteoarthritis (OA), this double blind and randomized pilot study used a broad spectrum of clinical and laboratory parameters to investigate whether such beneficial effects could be detected in a canine experimental OA model. Dogs were divided into 2 groups: control group (n = 8) receiving a placebo, and test group (n = 7) receiving orally 400 IU/ animal/ day of VE during 55 days, starting the day after transection surgery of the cranial cruciate ligament. At d56, dogs were euthanized and concentrations of prostaglandin E2 (PGE2), nitric oxide (NO) and interleukin-1β (IL-1β) were measured in synovial fluid samples. Severity of lameness and pain was assessed using a visual analogue scale (VAS), a numerical rating scale (NRS) and electrodermal activity (EDA) at d0, d28 and d55. The size and grade of cartilage macroscopic lesions on femoral condyles and tibial plateaus were evaluated, and the histological severity of cartilage lesions and synovial inflammation was determined. One-side comparison was conducted at an alpha-threshold of 10%. Synovial amounts of NOx and PGE2 were lower in the test group (P < 0.0001 and P = 0.03, respectively). Values of VAS, NRS and EDA showed a consistent trend to be lower in the test group compared to the control, while statistical significance was reached for VAS at d55 and EDA at d28 (adjusted P = 0.07 in both cases). Histological analyses of articular cartilage showed a significant reduction in lesions’ scores in the tested group. For the first time, a study in dog with OA using high dose of VE showed that this supplementation reduces inflammation joint markers and histological expression, as well as tends to improve signs of pain

Évaluation in vivo de l’efficacité thérapeutique, de la résistance et la pharmacocinétique de la colistine sulfate lors du traitement de la diarrhée colibacillaire post sevrage chez le porc

La diarrhée colibacillaire post-sevrage (DCPS) est une infection intestinale endémique dans les fermes porcines à l’échelle mondiale. Cette maladie est causée principalement par la présence et la multiplication au niveau de l’intestin des porcelets d’un pathotype d’Escherchia coli, nommé E. coli entérotoxinogène (ETEC) et en particulier celui qui exprime l’adhésine F4 (K88) (ETEC: F4). Le sérogroupe ETEC: O149 a été le plus isolé à partir des cas de DCPS à travers le monde. Plusieurs études ont rapporté un taux de résistance important des souches O149: F4 contre les antibiotiques qui sont classiquement utilisés pour traiter cette infection et en particulier les aminoglycosides. Ainsi, pour remédier aux échecs thérapeutiques observés dans les fermes porcines au Canada, les vétérinaires ont commencé à utiliser, sous leurs responsabilités, un antibiotique, la colistine sulfate (CS), qui n’est pas homologué en production animale au Canada. Cette étude avait pour buts d’étudier la pharmacocinétique de la CS in vitro et in vivo, de développer une technique sensible pour une quantification plasmatique de la CS, de déterminer son efficacité thérapeutique in vivo dans un modèle d’infection expérimentale de DCPS et de caractériser la résistance d’E. coli consécutive à l’utilisation thérapeutique de la CS chez le porc. Une simulation du liquide gastrique (SLG) a été préparée, et après l’ajout de la CS et de la pepsine à cette solution, les concentrations de la CS ont été mesurées par chromatographie liquide à haute performance couplée à la spectrométrie de masse en tandem (HPLC-MS/MS). Une dégradation rapide de CS a été constatée dans la SLG et a été accompagnée par la formation de produits de dégradation qui ont démontré une activité microbienne plus importante par comparaison avec la molécule mère (CS). Dans un volet in vivo, l’infection expérimentale des porcelets sevrés par une souche ETEC: F4 n’a pas augmenté l’absorption digestive de la CS dans un modèle subclinique de DCPS chez le porc. L’administration orale de la CS à la dose thérapeutique de 50,000 UI/kg à raison de 2 fois par jour pendant 5 jours pour traiter la DCPS dans des conditions expérimentales a entraîné une réduction significative de l’excrétion fécale de la souche infectieuse (ETEC : F4), de la population totale d’E. coli et des scores de diarrhée, uniquement pendant la période du traitement. Cependant, ces résultats ont été accompagnés par une légère augmentation dans l’excrétion fécale des E. coli résistants à la colistine, et le traitement n'a pas empêché la perte de poids des porcs infectés. En revanche, l’infection expérimentale des porcelets par ETEC: F4 a augmenté l’absorption digestive de la CS dans un modèle clinique de diarrhée colibacillaire chez le porc. Cette étude a permis de générer pour la première fois des données scientifiques concernant l’efficacité thérapeutique, la pharmacocinétique et la résistance à la colistine dans un modèle de DCPS chez le porc. Elle a également remis en doute la pertinence économique d’augmenter la dose de CS pour accélérer le rétablissement clinique des porcs. Finalement, elle a indiqué que des conditions d’élevage optimales, sans autres facteurs prédisposants, étaient aussi efficaces que la CS dans l’amélioration des symptômes cliniques de la DCPS.Post-weaning diarrhea (PWD) caused by Escherichia coli is an endemic intestinal infection in pig farms worldwide. This disease is mostly the consequence of the presence and the multiplication in piglet’s gut of an Escherchia pathotype, named enterotoxigenic E. coli (ETEC) and in particular those that express the F4 (K88) fimbrial adhesin (ETEC: F4). The predominant serogroup of E. coli isolated from piglets with PWD worldwide is O149. Several studies have reported a significant resistance rate of O149 ETEC strains against commonly used antibiotics for the treatment of PWD, particularly, aminoglycosides. Thereby, to address therapeutic failures observed in pig farms during PWD treatment, veterinarians in Canada started using, under their responsibilities, the colistin sulfate (CS), an antibiotic not approved for farm animals in Canada. The objectives of this thesis were: to study the pharmacokinetics of CS in vitro and in vivo, to develop a sensitive method for the quantification of CS plasma concentrations in pigs, to determine the therapeutic efficacy of CS in an experimental model of PWD, and to characterize the resistance of E. coli to colistin consecutive to its therapeutic use in pigs. Simulated gastric fluid (SGF) was prepared, and after the addition of CS and pepsin to this solution, the concentrations of CS were followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A rapid degradation of CS in the SGF was observed, and the degradation products showed a greater antimicrobial activity compared to the native CS. On the other hand, the experimental challenge of piglets with an ETEC: F4 strain has not increased the CS intestinal absorption in a subclinical model of PWD in pigs. The oral administration of a therapeutic dose of CS at 50,000 IU/kg twice a day for 5 successive days to treat an experimental PWD in pigs, resulted in a significant reduction of fecal ETEC: F4 and total E. coli shedding, and in diarrhea scores but only during the treatment period. However, CS treatment resulted in a slight increase in fecal shedding of CS resistant E. coli and did not prevent weight loss in challenged pigs. In addition, challenge with ETEC: F4 resulted in an increase of CS intestinal absorption in a clinical model of PWD. This study has generated, for the first time, scientific data regarding CS therapeutic efficacy, its pharmacokinetic and the selection of E. coli colistin resistant in an experimental model of PWD in pigs. It also challenged the economic relevance of increasing CS oral doses to accelerate the clinical recovery of pigs. Finally, it indicated that optimal housing conditions were without other predisposing factors, effective as CS in improving clinical symptoms of experimental PWD in pigs

Post weaning diarrhea in pigs: risk factors and non‑colistin‑based control strategies

Post-weaning diarrhea (PWD) is one of the most serious threats for the swine industry worldwide. It is commonly associated with the proliferation of enterotoxigenic Escherichia coli in the pig intestine. Colistin, a cationic antibiotic, is widely used in swine for the oral treatment of intestinal infections caused by E. coli, and particularly of PWD. However, despite the effectiveness of this antibiotic in the treatment of PWD, several studies have reported high rates of colistin resistant E. coli in swine. Furthermore, this antibiotic is considered of very high importance in humans, being used for the treatment of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB). Moreover, the recent discovery of the mcr-1 gene encoding for colistin resistance in Enterobacteriaceae on a conjugative stable plasmid has raised great concern about the possible loss of colistin effectiveness for the treatment of MDR-GNB in humans. Consequently, it has been proposed that the use of colistin in animal production should be considered as a last resort treatment only. Thus, to overcome the economic losses, which would result from the restriction of use of colistin, especially for prophylactic purposes in PWD control, we believe that an understanding of the factors contributing to the development of this disease and the putting in place of practical alternative strategies for the control of PWD in swine is crucial. Such alternatives should improve animal gut health and reduce economic losses in pigs without promoting bacterial resistance. The present review begins with an overview of risk factors of PWD and an update of colistin use in PWD control worldwide in terms of quantities and microbiological outcomes. Subsequently, alternative strategies to the use of colistin for the control of this disease are described and discussed. Finally, a practical approach for the control of PWD in its various phases is proposed

Morphological variability of Mauritanian date-palm (Phoenix dactylifera L.) cultivars as revealed by vegetative traits

The aim of this study was to use morphological markers to characterize twelve Mauritanian date-palm ecotypes currently grown by farmers. Eighteen phenotypic traits describing the vegetative systems were measured in the field in Atar Oasis. The data set was analyzed by principal components analysis (PCA) and UPGMA clustering. PCA revealed a great variability among the cultivars. Fourteen out of the 18 characters studied showed a high discriminating power suggesting their possible uses in the establishment of a Mauritanian date-palm catalogue. UPGMA Clustering revealed association between cultivars with similar fruit characteristics indicating that these ecotypes are morphologically related. Results also showed that individuals belonging to the Ahmar cultivar were morphologically distinct, suggesting it is likely a polyclonal variety

Efficacy of fungicides for control of powdery mildew on grapevines in Chott Sidi Abdel Salam oasis, southeastern Tunisia

Grapevine is an important fruit crop grown in the Chott Sidi Abdel Salam oasis in south eastern Tunisia. It provides great economic potential for the oasis population due to its higher yield and monetary returns. It, also, has a good nutritional value and is consumed fresh or in dried form. Powdery mildew represents one of the most destructive diseases affecting viticulture, especially in temperate-humid climate. It is an economically important fungal disease in the grapevine farms. This pathogen is able to differentially attack leaves and grapes, and is currently controlled with repeated applications of fungicides. This research aimed to use chemical control in order to assess the ability of contact, systemic and the combination of both routes of fungicides’ administration, at three different sampling moments to manage powdery mildew infestation of grapevines (Cv. Bazzoul Kalba), under field conditions. The experiments were conducted in the oasis of Chott Sidi Abdel Salam in southeastern Tunisia. Both Pristine WG and Vectra 10 SC allowed controlling the disease intensity of powdery mildew compared to Talendo® showing a highly significant augmentation of the inhibitory growth potential (84.26% and 88.94%, respectively at 21 days after the first fungicide application) and the protective potential (73.11% and 76.92%, respectively at 21 day). This information can be used to help grapevines growers to improve powdery mildew control and enhance marketable yields

First report of olive anthracnose caused by Colletotrichum gloeosporioides in Tunisia

Ripe and overripe olive fruits (cv. Meski, Manzanilla and Picholine) showing circular spots 1 to 10 mm in diameter, slightly depressed and reddish-brown in color, were collected from local markets and orchards located in the regions of Takelsa, Zarzis and Rgueb in Tunisia. Colletotrichum gloeosporioides was isolated from symptomatic fruits and Koch&rsquo;s postulates were fulfilled. This is the first report of Colletotrichum gloeosporioides causing anthracnose of olives in Tunisia