The first report of the coproduction of CMY-16 and ArmA 16S rRNA methylases in carbapenemase-ESBL producing Escherichia coli isolates

The main aim of this work was to assess the occurrence and to characterize AmpC genes and to investigate the co-existence of 16S rRNA methylases and carbapenemases genes among the ESBL producing Escherichia coli strains. 180 Escherichia coli clinical strains were collected from the university hospital of Constantine located in the eastern part of Algeria. 42 ESBL-producers were phenotypically identified and also confirmed genotypically able to produce CTX-M-15 [n=33], CTX-M-1 [n=5], CTX-M-14 [n=1], SHV-2 [n=1], and two strains have been revealed producing the blaOXA-48 genes associated with blaTEM-1. Among the ESBL-producing strains three expressed additionally an AmpC phenotype which corresponded to the carriage of a blaCMY gene shown by sequencing to correspond to CMY-2 (1 isolate) CMY-16 (2 isolates). The two E. coli isolates produce CMY-16 that belonged to phylogroup D while the single CMY-2 producing isolate belonged to phylogroup C. Antibiotic resistance of the aminoglycoside family by production of 16S rRNA methylases was detected by an end-point multiplex PCR assay which concerns genes coding for different 16S rRNA methylases (rmtD, rmtA, rmtB, armA, npmA, and rmtC). An armA gene was identified in 2 strains. This study shows for the first time the co-existance of CMY-16 and armA genes with blaTEM-1 and blaOXA-48 producing E. coli strains. DOI: http://dx.doi.org/10.5281/zenodo.377665

Évaluation de l’exposition du patient adulte aux particules issues des incompatibilités entre médicaments injectables utilisés en anesthésie et réanimation

Our PhD work aimed to evaluate the particulate exposure induced by drug incompatibilities in patients admitted in ICU for a septic shock or acute respiratory distress syndrome. The purpose was to establish a link with the occurrence of certain complications (inflammatory syndrome and organ dysfunctions) susceptible to aggravate life threatening. Indeed, the microcirculatory dysfunction characteristic of these patients could be increased by the particulate contamination, compromising tissue perfusion and leading to the occurrence of multi organ failureThe first part of this study consisted in a systematic literature review on the clinical implications of drug incompatibilities. One of the essential messages is the growing interest of inline filtration to prevent particulate contamination, highlighted by randomized controlled trials especially in pediatric ICU.The second part of the study was to conduct, in a first phase, an observational study, at the ICU patients’ bedsides, of the commonly used intravenous drugs and infusion sets. The second phase was to reproduce in vitro the previous observed infusion lines using the observed drugs combination, in order to quantify the particulate exposure, during a simulated 6-hour infusion period. The particle counting was performed using an innovative dynamic image analysis device.Our work indicates the amount of particulate matter potentially administered to critically-ill adult patients and paves the way to a strategy of prevention of drug incompatibilities.Ce travail de doctorat s’inscrit dans un projet de recherche destiné à évaluer la charge particulaire issue des incompatibilités physico-chimiques d’origine médicamenteuse de patients admis en réanimation pour un état de choc septique ou un syndrome de détresse respiratoire aigüe. Le corollaire est de faire le lien avec la survenue de certaines complications (syndrome inflammatoire et dysfonction d’organe) susceptibles de menacer le pronostic vital. En effet, la dysfonction microcirculatoire caractéristique de ces patients pourrait être majorée par la contamination particulaire aboutissant ainsi à une aggravation de l’hypo-perfusion tissulaire et à la survenue du syndrome de défaillance multi viscérale.La première partie de ce travail a consisté en une analyse de la littérature portant sur les incompatibilités médicamenteuses et leurs principales conséquences cliniques sous forme d’une revue systématique. Un des messages essentiels est l’intérêt grandissant de la filtration en ligne comme moyen de prévention de la contamination particulaire bien mis en évidence par certains essais contrôlés randomisés en particulier pédiatriques.La seconde partie de ce travail était de mener, dans une première phase, une étude d’observation clinique au lit du malade des dispositifs de perfusion intraveineux habituellement utilisés et des médicaments le plus souvent administrés à ces patients de réanimation du CHU de Lille. La deuxième phase consistait à reproduire in vitro le montage de perfusion utilisé en clinique avec les différentes solutions médicamenteuses dans le but de quantifier la charge particulaire à laquelle sont exposés les patients. Le comptage particulaire a été réalisé de manière dynamique, selon une technique innovante, grâce à un analyseur de particule connecté au montage de perfusion.Ce travail nous a permis finalement d’évaluer le risque particulaire pour ces patients fragiles et de proposer une stratégie de prévention des incompatibilités médicamenteuses

Assessment of particulate exposure induced by drug incompatibilities during continuous drug infusion in critically ill adult patients

Ce travail de doctorat s’inscrit dans un projet de recherche destiné à évaluer la charge particulaire issue des incompatibilités physico-chimiques d’origine médicamenteuse de patients admis en réanimation pour un état de choc septique ou un syndrome de détresse respiratoire aigüe. Le corollaire est de faire le lien avec la survenue de certaines complications (syndrome inflammatoire et dysfonction d’organe) susceptibles de menacer le pronostic vital. En effet, la dysfonction microcirculatoire caractéristique de ces patients pourrait être majorée par la contamination particulaire aboutissant ainsi à une aggravation de l’hypo-perfusion tissulaire et à la survenue du syndrome de défaillance multi viscérale.La première partie de ce travail a consisté en une analyse de la littérature portant sur les incompatibilités médicamenteuses et leurs principales conséquences cliniques sous forme d’une revue systématique. Un des messages essentiels est l’intérêt grandissant de la filtration en ligne comme moyen de prévention de la contamination particulaire bien mis en évidence par certains essais contrôlés randomisés en particulier pédiatriques.La seconde partie de ce travail était de mener, dans une première phase, une étude d’observation clinique au lit du malade des dispositifs de perfusion intraveineux habituellement utilisés et des médicaments le plus souvent administrés à ces patients de réanimation du CHU de Lille. La deuxième phase consistait à reproduire in vitro le montage de perfusion utilisé en clinique avec les différentes solutions médicamenteuses dans le but de quantifier la charge particulaire à laquelle sont exposés les patients. Le comptage particulaire a été réalisé de manière dynamique, selon une technique innovante, grâce à un analyseur de particule connecté au montage de perfusion.Ce travail nous a permis finalement d’évaluer le risque particulaire pour ces patients fragiles et de proposer une stratégie de prévention des incompatibilités médicamenteuses.Our PhD work aimed to evaluate the particulate exposure induced by drug incompatibilities in patients admitted in ICU for a septic shock or acute respiratory distress syndrome. The purpose was to establish a link with the occurrence of certain complications (inflammatory syndrome and organ dysfunctions) susceptible to aggravate life threatening. Indeed, the microcirculatory dysfunction characteristic of these patients could be increased by the particulate contamination, compromising tissue perfusion and leading to the occurrence of multi organ failureThe first part of this study consisted in a systematic literature review on the clinical implications of drug incompatibilities. One of the essential messages is the growing interest of inline filtration to prevent particulate contamination, highlighted by randomized controlled trials especially in pediatric ICU.The second part of the study was to conduct, in a first phase, an observational study, at the ICU patients’ bedsides, of the commonly used intravenous drugs and infusion sets. The second phase was to reproduce in vitro the previous observed infusion lines using the observed drugs combination, in order to quantify the particulate exposure, during a simulated 6-hour infusion period. The particle counting was performed using an innovative dynamic image analysis device.Our work indicates the amount of particulate matter potentially administered to critically-ill adult patients and paves the way to a strategy of prevention of drug incompatibilities

Potential Use of Propolis in Phytocosmetic as Phytotherapeutic Constituent

Phytocosmetic is an important aspect of traditional medicine in several cultures. Researchers are now focusing to find new and effective ingredients of natural origin. Propolis is a natural beehive product extensively used in traditional medicine. We aimed in the present study to investigate the potential use of propolis as an aesthetic and phytotherapeutic constituent in phytocosmetics. Propolis was extracted using 80% ethanol. Total phenolic and flavonoid contents were determined calorimetrically. Free radical scavenging ability and reducing capacity were evaluated using four assays and expressed as IC50 values. Antibacterial activity was evaluated by the determination of minimum inhibitory concentration (MIC) on 11 Gram-positive and Gram-negative bacteria. The wound healing activity of 30% ethanolic extract and propolis ointment was studied using excision wounds in the anterio-dorsal side of the rats. The phenolic acid composition of the tested propolis was investigated using UFLC/MS-MS analysis. The tested propolis was rich in phenolic and flavonoid content and demonstrated an interesting antibacterial and antioxidant activity. Wounds treated with propolis appear to display a lesser degree of inflammation. Chemical analysis led to the identification of 11 phenolics. Among them, five are considered as main compounds: Chlorogenic acid (48.79 ± 5.01 ng/mL), Gallic acid (44.25 ± 6.40 ng/mL), Rutin (21.12 ± 3.57 ng/mL), Caffeic acid (28.19 ± 4.95 ng/mL), and trans-cinnamic acid (20.10 ± 6.51 ng/mL). Our results indicated that propolis can not only be used as a cosmetic ingredient but also be used as a preventative and curative constituent, which might be used as a barrier when applied externally on infected and non-infected skin

Prostaglandin E1 increases oxygen extraction capabilities in experimental sepsis

By its microvascular and anti-inflammatory actions, prostaglandin E1 (PGE1) has been suggested both in animal models and in humans to have a therapeutic value in sepsis. To investigate whether PGE1 could improve the oxygen extraction capabilities in severe sepsis, our study focused on the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during an acute reduction in blood flow induced by cardiac tamponade in endotoxic dogs. Thirty anesthetized, ventilated dogs were divided into three groups. A first group (N = 10) served as a control receiving 20 ml/kg/hr of saline intravenously. A second group (N = 10) received PGE1 at 100 ng/kg/min along with the same saline infusion. A third group (N = 10) received the same dose of PGE1 with only 1 ml/kg/hr of saline. Thirty minutes after the initiation of this therapy, Escherichia coli endotoxin (2 mg/kg) was injected in each dog. In each group, the administration of PGE1, fluids, or both was continued throughout the study. Tamponade was then induced by repeated bolus injections of warm saline into the pericardial space. Steady-state measurements of VO2 (derived from the expired gases) and DO2 (the product of cardiac index and oxygen content) were obtained sequentially after each saline injection. The administration of PGE1 + fluids resulted in significant increases in stroke volume, cardiac index, and DO2 and reductions in systemic and pulmonary vascular resistance. Stroke volume and cardiac index were lower in the PGE1 alone than in the PGE1 + fluids group. The VO2 levels at critical DO2 (DO2crit) were identical. However, DO2crit, which was 12.2 +/- 2.8 ml/kg/min in the control group, was significantly decreased to 9.8 +/- 2.0 ml/kg/min in the PGE1 + fluids and to 9.3 +/- 2.7 ml/kg/min in the PGE1 alone group (both P < 0.05). Critical oxygen extraction ratio (O2ERcrit) which was 47 +/- 14% in the control group, was increased to 63 +/- 16% in the PGE1 + fluids group and to 61 +/- 17% in the PGE1 alone group (both P < 0.05). To investigate whether PGE1 also improves oxygen extraction capabilities in the absence of endotoxin, a second series of experiments was performed in 14 dogs, receiving saline alone (Control, N = 7) or plus PGE1 at 100 ng/kg/min (PGE1, N = 7). DO2crit was 10.7 +/- 2.9 ml/kg/min in the PGE1 group vs 10.1 +/- 1.8 ml/kg/min in the control group (NS). O2ERcrit tended to be higher in the PGE1 group than that in the control group (68 +/- 13% vs 60 +/- 15%, P = 0.054)

Protective effects of N-acetyl-L-cysteine in endotoxemia.

Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/- 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS

Systemic oxygen extraction can be improved during repeated episodes of cardiac tamponade

We used a tamponade model to study the relationship between oxygen uptake (Vo2) and oxygen delivery (Do2) during successive, reversible decreases in blood flow. In 7 pentobarbital-anesthetized and mechanically ventilated dogs, a catheter was introduced via a left thoracotomy into the pericardium to inject and to withdraw saline. Each experiment consisted of three steps. First, cardiac output was reduced by successive pericardial fluid injections until 4 to 6 data points were obtained in the dependent region of the Vo2/Do2 plot (step 1). Second, cardiac output was restored by progressive withdrawal of pericardial fluid (step 2). Third, cardiac output was lowered again by reinjection of fluid into the pericardium until death (step 3). Expired gases were collected for determination of Vo2. In each animal, critical Do2 (Do2crit), below which Vo2 became Do2 dependent, was determined from a plot of Vo2 versus Do2. When releasing tamponade, Vo2 was restored to baseline. For the 3 steps, Do2crit were 10.5 ± 2.2 mL/kg/min in step 1, 9.8 ± 1.8 mL/kg/min in step 2, and 8.3 ± 1.9 mL/kg/min in step 3 (P < .01 v step 1; P < .05 v step 2, respectively). There was no significant difference in Vo2 at Do2crit for the three steps. Hence, critical oxygen extraction ratio (ERo2crit) increased from 60% ± 12% in step 1 to 64% ± 11% in step 2 (not significant) and to 73% ± 12% in step 3 (P < .01). The Vo2/Do2 dependency slope was also steeper in step 3 than in step 1 (0.77 ± 0.31 v 0.54 ± 0.20, P < .05). A progressive decrease in arterial and in mixed venous pH was observed during the experiment. We conclude that a decrease in Vo2 associated with an acute reduction in blood flow can be readily reversible. When the procedure is repeated, a progressive increase in oxygen extraction capabilities is observed. This reversible tamponade model is potentially suitable to induce several hypoxic episodes in the same animal.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A new triterpenic diester from the aerial parts of Chrysanthemum macrocarpum

International audienceA new triterpenic diester, 3,21-dipalmitoyloxy-16β,21α-dihydroxy-β-amyrine (1), along with two natural cyclitols, conduritol C (2) and viburnitol (3), four known triterpenes (4–7), and seven known flavonoids (8–14) were isolated from the aerial parts of Chrysanthemum macrocarpum. Their structures were established on the basis of extensive 1D and 2D NMR (1H, 13C, COSY, HMBC, HSQC, and ROESY) and ESIMS studies. The chloroform fraction, taraxasterol (4) and β-sitosterol (7) were investigated for their antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The chloroform fraction and taraxasterol (4) showed a weak antibacterial activity and were evaluated for their cytotoxic activity against human colon cancer HT-29 cells and human prostate carcinoma PC3 cells. The results indicated that both the chloroform fraction and taraxasterol (4) inhibited cell proliferation of both PC3 and HT-29 cells

First report of blaOXA-24 carbapenemase gene, armA methyltransferase and aac(6′)-Ib-cr among multidrug-resistant clinical isolates of Proteus mirabilis in Algeria

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