scholarly journals Genotypic and Phenotypic Evaluation of the Evolution of High-Level Daptomycin Nonsusceptibility in Vancomycin-Resistant Enterococcus faecium

2012 ◽  
Vol 56 (11) ◽  
pp. 6051-6053 ◽  
Author(s):  
Romney M. Humphries ◽  
Theodoros Kelesidis ◽  
Ryan Tewhey ◽  
Warren E. Rose ◽  
Nicholas Schork ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Open Reading Frames ◽  
Vancomycin Resistant Enterococcus ◽  
Single Nucleotide Variants ◽  
Phosphotransferase System ◽  
Single Nucleotide ◽  
Content Type ◽  
Vancomycin Resistant ◽  
High Level ◽  
Reading Frames

ABSTRACTWhole-genome sequencing and cell membrane studies of three clonalEnterococcus faeciumstrains with daptomycin MICs of 4, 32, and 192 μg/ml were performed, revealing nonsynonymous single nucleotide variants in eight open reading frames, including those predicted to encode a phosphoenolpyruvate-dependent, mannose-specific phosphotransferase system, cardiolipin synthetase, and EzrA. Membrane studies revealed a higher net surface charge among the daptomycin-nonsusceptible isolates and increased septum formation in the isolate with a daptomycin MIC of 192 μg/ml.

scholarly journals Homologous Recombination within Large Chromosomal Regions Facilitates Acquisition of β-Lactam and Vancomycin Resistance in Enterococcus faecium

2016 ◽  
Vol 60 (10) ◽  
pp. 5777-5786 ◽  
Author(s):  
Mónica García-Solache ◽  
Francois Lebreton ◽  
Robert E. McLaughlin ◽  
James D. Whiteaker ◽  
Michael S. Gilmore ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Genomic Dna ◽  
Large Scale ◽  
Vancomycin Resistance ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Single Nucleotide ◽  
Content Type ◽  
Donor Chromosome ◽  
Vancomycin Resistant

ABSTRACTThe transfer of DNA betweenEnterococcus faeciumstrains has been characterized both by the movement of well-defined genetic elements and by the large-scale transfer of genomic DNA fragments. In this work, we report on the whole-genome analysis of transconjugants resulting from mating events between the vancomycin-resistantE. faeciumC68 strain and the vancomycin-susceptible D344RRF strain to discern the mechanism by which the transferred regions enter the recipient chromosome. Vancomycin-resistant transconjugants from five independent matings were analyzed by whole-genome sequencing. In all cases but one, the penicillin binding protein 5 (pbp5) gene and the Tn5382vancomycin resistance transposon were transferred together and replaced the correspondingpbp5region of D344RRF. In one instance, Tn5382inserted independently downstream of the D344RRFpbp5gene. Single nucleotide variant (SNV) analysis suggested that entry of donor DNA into the recipient chromosome occurred by recombination across regions of homology between donor and recipient chromosomes, rather than through insertion sequence-mediated transposition. The transfer of genomic DNA was also associated with the transfer of C68 plasmid pLRM23 and another putative plasmid. Our data are consistent with the initiation of transfer by cointegration of a transferable plasmid with the donor chromosome, with subsequent circularization of the plasmid-chromosome cointegrant in the donor prior to transfer. Entry into the recipient chromosome most commonly occurred across regions of homology between donor and recipient chromosomes.

scholarly journals High Prevalence ofvanMin Vancomycin-Resistant Enterococcus faecium Isolates from Shanghai, China

2015 ◽  
Vol 59 (12) ◽  
pp. 7795-7798 ◽  
Author(s):  
Chunhui Chen ◽  
Jingyong Sun ◽  
Yan Guo ◽  
Dongfang Lin ◽  
Qinglan Guo ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Enterococcus Faecium ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
High Prevalence ◽  
Vancomycin Resistant ◽  
Susceptibility Patterns

ABSTRACTThevanMgene was first found in a vancomycin-resistantEnterococcus faecium(VREm) isolate in Shanghai in 2006. In this study, we found that, in 70 VREm strains isolated in nine Shanghai hospitals from 2006 to 2014,vanMwas more prevalent than thevanAgene (64.3% [45/70] versus 35.7% [25/70]). ThevanM-type isolates showed similar antimicrobial susceptibility patterns with thevanAtypes. ThevanM-type VREm emerged and disseminated in Shanghai.

scholarly journals β-Lactams Enhance Daptomycin Activity against Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium inIn VitroPharmacokinetic/Pharmacodynamic Models

2015 ◽  
Vol 59 (5) ◽  
pp. 2842-2848 ◽  
Author(s):  
Jordan R. Smith ◽  
Katie E. Barber ◽  
Animesh Raut ◽  
Michael J. Rybak
Keyword(s):  
Body Weight ◽  
Combination Therapy ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Single Agent ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Combination Regimens

ABSTRACTEnterococcus faecalisandEnterococcus faeciumare frequently resistant to vancomycin and β-lactams. In enterococcal infections with reduced glycopeptide susceptibility, combination therapy is often administered. Our objective was to conduct pharmacokinetic/pharmacodynamic (PK/PD) models to evaluate β-lactam synergy with daptomycin (DAP) against resistant enterococci. OneE. faecalisstrain (R6981) and twoE. faeciumstrains (R6370 and 8019) were evaluated. DAP MICs were obtained. All strains were evaluated for response to LL37, an antimicrobial peptide, in the presence and absence of ceftaroline (CPT), ertapenem (ERT), and ampicillin (AMP). After 96 h,in vitromodels were run simulating 10 mg DAP/kg body weight/day, 600 mg CPT every 8 h (q8h), 2 g AMP q4h, and 1 g ERT q24h, both alone and in combination against all strains. DAP MICs were 2, 4, and 4 μg/ml for strains R6981, R6370, and 8019, respectively. PK/PD models demonstrated bactericidal activity with DAP-CPT, DAP-AMP, and DAP-ERT combinations against strain 8019 (P< 0.001 and log10CFU/ml reduction of >2 compared to any single agent). Against strains R6981 and R6370, the DAP-AMP combination demonstrated enhancement against R6370 but not R6981, while the combinations of DAP-CPT and DAP-ERT were bactericidal, demonstrated enhancement, and were statistically superior to all other regimens at 96 h (P< 0.001) against both strains. CPT, ERT, and AMP similarly augmented LL37 killing against strain 8019. In strains R6981 and R6370, CPT and ERT aided LL37 more than AMP (P< 0.001). Compared to DAP alone, combination regimens provide better killing and prevent resistance. Clinical research involving DAP combinations is warranted.

scholarly journals Draft Genome Sequence of New Vancomycin-Resistant Enterococcus faecium Sequence Type 1421

2018 ◽  
Vol 6 (20) ◽  
Author(s):  
Kelvin W. C. Leong ◽  
Louise A. Cooley ◽  
Ronan F. O’Toole
Keyword(s):  
Genome Sequence ◽  
Enterococcus Faecium ◽  
Draft Genome ◽  
Sequence Type ◽  
Public Hospitals ◽  
Whole Genome Sequence ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Type Sequence

ABSTRACT The spread of vancomycin-resistant Enterococcus faecium (VREfm) has become a challenge to health care infection control worldwide. In 2015, a marked increase in VREfm isolation was detected in acute public hospitals in Tasmania. We report here the draft whole-genome sequence of a newly designated VREfm sequence type, sequence type 1421 (ST1421).

scholarly journals Vancomycin-resistant Enterococcus faecium in Algeria: phenotypic and genotypic characterization of clinical isolates

2021 ◽  
Vol 15 (01) ◽  
pp. 95-101
Author(s):  
Nabila Benamrouche ◽  
Badia Guettou ◽  
Fatma Zohra Henniche ◽  
Farida Assaous ◽  
Houcine Laouar ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Public Health Problem ◽  
Test Method ◽  
Control Measures ◽  
Molecular Characteristics ◽  
Major Public Health Problem ◽  
Vancomycin Resistant Enterococcus ◽  
Infection Control Measures ◽  
Vancomycin Resistant ◽  
High Level

Introduction: vancomycin-resistant Enterococcus faecium (VREfm) is a major public health problem worldwide. The aim of our study was to determine the microbiological, epidemiological and molecular characteristics of VREfm isolated in north-central, eastern and western Algeria. Methodology: a collection of 48 VREfm isolated from September 2010 to April 2017 in several Algerian hospitals were studied. Minimum inhibitory concentrations (MICs) were determined by E-test method according to CLSI guidelines. the detection of van genotype of all strains was performed by PCR. Clonal relationship of five VREfm targeted by region were characterized using multilocus sequence typing (MLST). Results: All isolates have multidrug-resistance (MDR) and were resistant to at least five classes of antibiotics; however, all were susceptible to tigecycline and daptomycin with MIC50 at 0.094 µg/mL and 2 µg/mL respectively. All strains belonged to vanA genotype and have high level of resistance to vancomycin and teicoplanin. MLST revealed two sequence types (STs): ST80 (from the four regions of Algeria) and ST789, both belonging to the former hospital-adapted clonal complex CC17. Conclusions: the alarming dissemination of MDR E. faecium vanA and the ST80 in several regions of Algeria suggest a clonal spread of VREfm strains, which urgently require implementation of adequate infection control measures.

scholarly journals Genomics of vancomycin-resistant Enterococcus faecium

2019 ◽  
Vol 5 (7) ◽  
Author(s):  
Claire Gorrie ◽  
Charlie Higgs ◽  
Glen Carter ◽  
Timothy P. Stinear ◽  
Benjamin Howden
Keyword(s):  
Enterococcus Faecium ◽  
Type Species ◽  
Treatment Options ◽  
World Health ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
The World ◽  
Significant Public Health ◽  
Vancomycin Resistant ◽  
New Treatments

Vancomycin-resistant Enterococcus faecium (VREfm) is a globally significant public health threat and was listed on the World Health Organization’s 2017 list of high-priority pathogens for which new treatments are urgently needed. Treatment options for invasive VREfm infections are very limited, and outcomes are often poor. Whole-genome sequencing is providing important new insights into VREfm evolution, drug resistance and hospital adaptation, and is increasingly being used to track VREfm transmission within hospitals to detect outbreaks and inform infection control practices. This mini-review provides an overview of recent data on the use of genomics to understand and respond to the global problem of VREfm.

scholarly journals Treatment of Multidrug-Resistant Vancomycin-Resistant Enterococcus faecium Hardware-Associated Vertebral Osteomyelitis with Oritavancin plus Ampicillin

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Samira Dahesh ◽  
Brian Wong ◽  
Victor Nizet ◽  
George Sakoulas ◽  
Truc T. Tran ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Antimicrobial Peptide ◽  
Continuous Infusion ◽  
Enterococcus Faecium ◽  
Vertebral Osteomyelitis ◽  
Multidrug Resistant ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Time Kill

ABSTRACT Weekly oritavancin plus ampicillin continuous infusion combination therapy was used to successfully treat a deep spine vancomycin-resistant Enterococcus faecium infection associated with hardware. Checkerboard and time-kill assays confirmed synergy between these two antibiotics. Further synergies of oritavancin and ampicillin with rifampin or the endogenous human antimicrobial peptide cathelicidin LL-37 were demonstrated.

scholarly journals Evaluation of Oritavancin Dosing Strategies against Vancomycin-Resistant Enterococcus faecium Isolates with or without Reduced Susceptibility to Daptomycin in an In Vitro Pharmacokinetic/Pharmacodynamic Model

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Adam Belley ◽  
Francis F. Arhin ◽  
Greg Moeck
Keyword(s):  
Enterococcus Faecium ◽  
Pharmacodynamic Model ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Vancomycin Resistant ◽  
Lipopeptide Antibiotic ◽  
Long Acting

ABSTRACT The clinical development of nonsusceptibility to the lipopeptide antibiotic daptomycin remains a serious concern during therapy for infections caused by vancomycin-resistant Enterococcus faecium (VREfm). The long-acting lipoglycopeptide oritavancin exhibits potent in vitro activity against VREfm, although its safety and efficacy for treating clinical VREfm infections have not been established. In this study, novel dosing regimens of daptomycin and oritavancin were assessed against both VREfm and daptomycin-nonsusceptible VREfm isolates in an in vitro pharmacokinetic/pharmacodynamic model.

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