scholarly journals Linezolid-resistant (Tn6246::fexB-poxtA) Enterococcus faecium strains colonizing humans and bovines on different continents: similarity without epidemiological link

2020 ◽  
Vol 75 (9) ◽  
pp. 2416-2423 ◽  
Author(s):  
Ana R Freitas ◽  
Ana P Tedim ◽  
Bárbara Duarte ◽  
Houyem Elghaieb ◽  
Mohamed S Abbassi ◽  
...  

Abstract Objectives poxtA is the most recently described gene conferring acquired resistance to linezolid, a relevant antibiotic for treating enterococcal infections. We retrospectively screened for poxtA in diverse enterococci and aimed to characterize its genetic/genomic contexts. Methods poxtA was screened by PCR in 812 enterococci from 458 samples (hospitals/healthy humans/wastewater/animals/retail food) obtained in Portugal/Angola/Tunisia (1996–2019). Antimicrobial susceptibility testing was performed for 13 antibiotics (EUCAST/CLSI). poxtA stability (∼500 generations), transfer (filter mating), clonality (SmaI-PFGE) and location (S1-PFGE/hybridization) were tested. WGS (Illumina-HiSeq) was performed for clonal representatives. Results poxtA was detected in Enterococcus faecium from six samples (1.3%): a healthy human (rectal swab) in Porto, Portugal (ST32/2001); four farm cows (milk) in Mateur, Tunisia (ST1058/2015); and a hospitalized patient (faeces) in Matosinhos, Portugal (ST1058/2015). All expressed resistance to linezolid (MIC = 8 mg/L), chloramphenicol, tetracycline and erythromycin, with variable resistance to ciprofloxacin and streptomycin. ST1058-poxtA-carrying isolates from Tunisia and Portugal differed by two SNPs and had similar plasmid content. poxtA, located in an IS1216-flanked Tn6246-like element, co-hybridized with fexB on one or more plasmids per isolate (one to three plasmids of 30–100 kb), was stable after several generations and transferred only from ST1058. ST1058 strains carried resistance/virulence genes (Efmqnr/acm) possibly induced under selective quinolone treatment. Conclusions poxtA has been circulating in Portugal since at least 2001, corresponding to the oldest description worldwide to date. We also extend the reservoir of poxtA to bovines. The similar linezolid-resistant poxtA-carrying strains colonizing humans and livestock on different continents, and without a noticeable relationship, suggests a recent transmission event or convergent evolution of E. faecium populations in different hosts and geographic regions.

2010 ◽  
Vol 54 (6) ◽  
pp. 2660-2665 ◽  
Author(s):  
Ana R. Freitas ◽  
Ana P. Tedim ◽  
Carla Novais ◽  
Patricia Ruiz-Garbajosa ◽  
Guido Werner ◽  
...  

ABSTRACT Enterococcus faecium has increasingly been reported as a nosocomial pathogen since the early 1990s, presumptively associated with the expansion of a human-associated Enterococcus faecium polyclonal subcluster known as clonal complex 17 (CC17) that has progressively acquired different antibiotic resistance (ampicillin and vancomycin) and virulence (esp Efm, hyl Efm, and fms) traits. We analyzed the presence and the location of a putative glycoside hydrolase hyl Efm gene among E. faecium strains obtained from hospitalized patients (255 patients; outbreak, bacteremic, and/or disseminated isolates from 23 countries and five continents; 1986 to 2009) and from nonclinical origins (isolates obtained from healthy humans [25 isolates], poultry [30], swine [90], and the environment [55]; 1999 to 2007). Clonal relatedness was established by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmid analysis included determination of content and size (S1-PFGE), transferability (filter mating), screening of Rep initiator proteins (PCR), and location of vanA, vanB, ermB, and hyl Efm genes (S1/I-CeuI hybridization). Most E. faecium isolates contained large plasmids (>150 kb) and showed variable contents of van, hyl Efm, or esp Efm. The hyl Efm gene was associated with megaplasmids (170 to 375 kb) of worldwide spread (ST16, ST17, and ST18) or locally predominant (ST192, ST203, ST280, and ST412) ampicillin-resistant CC17 clones collected in the five continents since the early 1990s. All but one hyl Efm-positive isolate belonged to the CC17 polyclonal subcluster. The presence of hyl Efm megaplasmids among CC17 from Europe, Australia, Asia, and Africa since at least the mid-1990s was documented. This study further demonstrates the pandemic expansion of particular CC17 clones before acquisition of vancomycin resistance and putative virulence traits and describes the presence of megaplasmids in most of the contemporary E. faecium isolates with different origins.


2013 ◽  
Vol 110 (1) ◽  
pp. 162-169 ◽  
Author(s):  
O. Le Bon ◽  
P. Linkowski

Previous studies in animals and humans have reported correlations between the durations of rapid eye movement sleep (REMS) episodes and immediately preceding or subsequent non-REMS (NREMS) episodes. The relationship between these two types of sleep is a crucial component in understanding the regulation and neurophysiology of ultradian alternations that occur during sleep. Although the present study replicated previous studies, we also measured NREMS in terms of spectral power Delta and Ultra-Slow bands in addition to duration in examining correlations. The spectral power Delta band, also known as slow-wave activity, measures sleep quantity and is believed to reflect sleep physiology better than mere episode durations. The Ultra-Slow spectral power band was analyzed in parallel. Healthy human participants of both sexes ( n = 26, age range 15–45 yr, n = 12 female) were carefully selected to participate in two consecutive series of home polysomnograms performed after 2 nights of habituation to the equipment. In the analyses, REMS episode durations (minutes) were compared with immediately preceding and immediately subsequent NREMS episodes (Delta and Ultra-Slow power) in each sleep cycle. REMS episode duration was more strongly correlated with preceding NREMS episodes than with subsequent NREMS episodes. However, in most cases, no correlations were observed in either direction. One ultradian sleep regulation hypothesis, which is based on stronger correlations between REMS and subsequent NREMS episode durations, holds that the main purpose of REMS is to reactivate NREMS during each sleep cycle. The present results do not support that hypothesis.


2012 ◽  
Vol 78 (16) ◽  
pp. 5824-5830 ◽  
Author(s):  
Catherine M. Logue ◽  
Curt Doetkott ◽  
Paul Mangiamele ◽  
Yvonne M. Wannemuehler ◽  
Timothy J. Johnson ◽  
...  

ABSTRACTNeonatal meningitisEscherichia coli(NMEC) is one of the top causes of neonatal meningitis worldwide. Here, 85 NMEC and 204 fecalE. coliisolates from healthy humans (HFEC) were compared for possession of traits related to virulence, antimicrobial resistance, and plasmid content. This comparison was done to identify traits that typify NMEC and distinguish it from commensal strains to refine the definition of the NMEC subpathotype, identify traits that might contribute to NMEC pathogenesis, and facilitate choices of NMEC strains for future study. A large number ofE. colistrains from both groups were untypeable, with the most common serogroups occurring among NMEC being O18, followed by O83, O7, O12, and O1. NMEC strains were more likely than HFEC strains to be assigned to the B2 phylogenetic group. Few NMEC or HFEC strains were resistant to antimicrobials. Genes that best discriminated between NMEC and HFEC strains and that were present in more than 50% of NMEC isolates were mainly from extraintestinal pathogenicE. coligenomic and plasmid pathogenicity islands. Several of these defining traits had not previously been associated with NMEC pathogenesis, are of unknown function, and are plasmid located. Several genes that had been previously associated with NMEC virulence did not dominate among the NMEC isolates. These data suggest that there is much about NMEC virulence that is unknown and that there are pitfalls to studying single NMEC isolates to represent the entire subpathotype.


2017 ◽  
Vol 22 (2) ◽  
pp. 91
Author(s):  
Laela Hayu Nurani ◽  
Eka Kumalasari ◽  
Abdul Rohman ◽  
Sitarina Widyarini

Pasak bumi (Eurycoma longifolia) has the potential to be developed as antihypertensive, antipyretic, aphrodisiacs and health supplements. The use of E. longifolia as a traditional medicine needs to be pursued in the form of more effective and appropriate formulation. The capsule preparations are easy to make and cancover the bitter taste of E. longifolia. Clinical trials in this study use design pre-post treatment in healthy humans. Subjects used were male - healthy men and healthy women who met inclusion criteria and were subjected with formulated capsule for 14 days. The study resulted capsule formula comprising of the ethanolic extract of E. longifolia 300 mg, vivapur 101 300 mg, 58 mg maydis starch, aerosil 3%, talc 2%, and Mg stearate 1%. The results showed that the capsule of E. longifolia did not affect the value of heart rate, respiration rate, body temperature and weight (P > 0.05), based on paired t-test, but they causes a decrease in blood pressure of healthy human. The ethanol extract of E. longifolia caused vasodilation of blood vessels that can be used in antihypertensive therapy.


2003 ◽  
Vol 284 (1) ◽  
pp. G130-G137 ◽  
Author(s):  
Heather J. Chial ◽  
Michael Camilleri ◽  
Duane Burton ◽  
George Thomforde ◽  
Kevin W. Olden ◽  
...  

This study evaluated the effects of serotonergic psychoactive agents on gastrointestinal functions in healthy human subjects. Participants received one of four regimens in a randomized, double-blind manner: buspirone, a 5-HT1Areceptor agonist (10 mg twice daily); paroxetine, a selective serotonin reuptake inhibitor (20 mg daily); venlafaxine-XR, a selective serotonin and norepinephrine reuptake inhibitor (75 mg daily); or placebo for 11 days. Physiological testing performed on days 8–11included scintigraphic assessment of gastrointestinal and colonic transit, the nutrient drink test, and assessment of the postprandial change in gastric volume. Fifty-one healthy adults (40 females, 11 males) participated in this study. No effects on gastric emptying or colonic transit were identified with any agent. Small bowel transit of a solid meal was accelerated by paroxetine. Buspirone decreased postprandial aggregate symptom and nausea scores. Venlafaxine-XR increased the postprandial change in gastric volume. Buspirone, paroxetine, and venlafaxine-XR affect upper gastrointestinal functions in healthy humans. These data support the need for clinical and physiological studies of these agents in functional gastrointestinal disorders.


2014 ◽  
Vol 58 (7) ◽  
pp. 3618-3625 ◽  
Author(s):  
Nina V. Malkevich ◽  
Robert J. Hopkins ◽  
Edward Bernton ◽  
Gabriel T. Meister ◽  
Eric M. Vela ◽  
...  

ABSTRACTAnthrax is an acute infectious disease caused by the spore-forming bacteriumBacillus anthracis. Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human anthrax monoclonal antibody), is being developed as a therapeutic agent against anthrax toxemia. The efficacy of AVP-21D9 inB. anthracis-infected New Zealand White rabbits and in cynomolgus macaques was evaluated, and its safety and pharmacokinetics were assessed in healthy human volunteers. The estimated mean elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11 days, respectively. In healthy humans, the mean elimination half-life was in the range of 20 to 27 days. Dose proportionality was observed for the maximum serum concentration (Cmax) of AVP-21D9 and the area under the concentration-time curve (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in survival of up to 92% of the rabbits and up to 67% of the macaques. Single infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all doses evaluated, and no serious adverse events were reported. (This study has been registered at ClinicalTrials.gov under registration no. NCT01202695.)


2014 ◽  
Vol 307 (7) ◽  
pp. R862-R868 ◽  
Author(s):  
Jennifer P. Richards ◽  
Gina L. C. Yosten ◽  
Grant R. Kolar ◽  
Cory W. Jones ◽  
Alan H. Stephenson ◽  
...  

ATP release from erythrocytes in response to reduced oxygen (O2) tension stimulates local vasodilation, enabling these cells to direct perfusion to areas in skeletal muscle in need of O2. Erythrocytes of humans with type 2 diabetes do not release ATP in response to low O2. Both C-peptide and insulin individually inhibit low O2-induced ATP release from healthy human erythrocytes, yet when coadministered at physiological concentrations and ratios, no inhibition is seen. Here, we determined: that 1) erythrocytes of healthy humans and humans with type 2 diabetes possess a C-peptide receptor (GPR146), 2) the combination of C-peptide and insulin at physiological ratios rescues low O2-induced ATP release from erythrocytes of humans with type 2 diabetes, 3) residual C-peptide levels reported in humans with type 2 diabetes are not adequate to rescue low O2-induced ATP release in the presence of 1 nM insulin, and 4) the effects of C-peptide and insulin are neither altered by increased glucose levels nor explained by changes in erythrocyte deformability. These results suggest that the addition of C-peptide to the treatment regimen for type 2 diabetes could have beneficial effects on tissue oxygenation, which would help to ameliorate the concomitant peripheral vascular disease.


2017 ◽  
Vol 11 (2) ◽  
pp. 83-89 ◽  
Author(s):  
Solayide A Adesida ◽  
Cynthia C Ezenta ◽  
Ajoke O Adagbada ◽  
Amudat A Aladesokan ◽  
Akintoye o Coker

2020 ◽  
Author(s):  
George A. Mashour ◽  
Ben J.A. Palanca ◽  
Mathias Basner ◽  
Duan Li ◽  
Wei Wang ◽  
...  

AbstractUnderstanding how consciousness and cognitive function return after a major perturbation is important clinically and neurobiologically. To address this question, we conducted a three-center study of 30 healthy humans receiving general anesthesia at clinically relevant doses for three hours. We administered a pre- and post-anesthetic battery of neurocognitive tests, recorded continuous electroencephalography to assess cortical dynamics, and monitored sleep-wake activity before and following anesthetic exposure. We hypothesized that cognitive reconstitution would be a process that evolved over time in the following sequence: attention, complex scanning and tracking, working memory, and executive function. Contrary to our hypothesis, executive function returned first and electroencephalographic analyses revealed that frontal cortical dynamics recovered faster than posterior cortical dynamics. Furthermore, actigraphy indicated normal sleep-wake patterns in the post-anesthetic period. These recovery patterns of higher cognitive function and arousal states suggest that the healthy human brain is resilient to the effects of deep general anesthesia.


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