Characteristic of Enterococcus faecium clinical isolates with quinupristin/dalfopristin resistance in China

The production of diverse and extended spectrum β-lactamases among Escherichia coli and ESKAPE pathogens is a growing threat to clinicians and public health. We aim to provide a comprehensive analysis of evolving trends of antimicrobial resistance and β-lactamases among E. coli and ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acine to bacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) in the Arabian region. A systematic review was conducted in Medline PubMed on papers published between January 2000 and February 2020 on countries in the Arab region showing different antibiotic resistance among E. coli and ESKAPE pathogens. A total of n = 119,144 clinical isolates were evaluated for antimicrobial resistance in 19 Arab countries. Among these clinical isolates, 74,039 belonged to E. coli and ESKAPE pathogen. Distribution of antibiotic resistance among E. coli and ESKAPE pathogens indicated that E. coli (n = 32,038) was the predominant pathogen followed by K. pneumoniae (n = 17,128), P. aeruginosa (n = 11,074), methicillin-resistant S. aureus (MRSA, n = 4370), A. baumannii (n = 3485) and Enterobacter spp. (n = 1574). There were no reports demonstrating Enterococcus faecium producing β-lactamase. Analyses revealed 19 out of 22 countries reported occurrence of ESBL (Extended-Spectrum β-Lactamase) producing E. coli and ESKAPE pathogens. The present study showed significantly increased resistance rates to various antimicrobial agents over the last 20 years; for instance, cephalosporin resistance increased from 37 to 89.5%, fluoroquinolones from 46.8 to 70.3%, aminoglycosides from 40.2 to 64.4%, mono-bactams from 30.6 to 73.6% and carbapenems from 30.5 to 64.4%. An average of 36.9% of the total isolates were reported to have ESBL phenotype during 2000 to 2020. Molecular analyses showed that among ESBLs and Class A and Class D β-lactamases, blaCTX-M and blaOXA have higher prevalence rates of 57% and 52.7%, respectively. Among Class B β-lactamases, few incidences of blaVIM 27.7% and blaNDM 26.3% were encountered in the Arab region. Conclusion: This review highlights a significant increase in resistance to various classes of antibiotics, including cephalosporins, β-lactam and β-lactamase inhibitor combinations, carbapenems, aminoglycosides and quinolones among E. coli and ESKAPE pathogens in the Arab region.

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Association of Alterations in ParC and GyrA Proteins with Resistance of Clinical Isolates of Enterococcus faecium to Nine Different Fluoroquinolones

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.10.2513 ◽

1999 ◽

Vol 43 (10) ◽

pp. 2513-2516 ◽

Cited By ~ 22

Author(s):

Sylvain Brisse ◽

Ad C. Fluit ◽

Ulrich Wagner ◽

Peter Heisig ◽

Dana Milatovic ◽

...

Keyword(s):

Enterococcus Faecium ◽

Resistance Mechanisms ◽

Clinical Isolates

ABSTRACT The parC and gyrA genes of 73 ciprofloxacin-resistant and 6 ciprofloxacin-susceptibleEnterococcus faecium clinical isolates were partly sequenced. Alterations in ParC and GyrA, possibly in combination with other resistance mechanisms, severely restricted the in vitro activities of the nine quinolones tested. For all isolates, clinafloxacin and sitafloxacin showed the best activities.

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High-level resistance to gentamicin in clinical isolates of Streptococcus (Enterococcus) faecium.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.32.10.1528 ◽

1988 ◽

Vol 32 (10) ◽

pp. 1528-1532 ◽

Cited By ~ 53

Author(s):

G M Eliopoulos ◽

C Wennersten ◽

S Zighelboim-Daum ◽

E Reiszner ◽

D Goldmann ◽

...

Keyword(s):

Enterococcus Faecium ◽

Clinical Isolates ◽

High Level ◽

Level Resistance

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Influence of Inoculum Effect on the Efficacy of Daptomycin Monotherapy and in Combination with β-Lactams against Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00315-18 ◽

2018 ◽

Vol 62 (8) ◽

Cited By ~ 11

Author(s):

Razieh Kebriaei ◽

Seth A. Rice ◽

Kavindra V. Singh ◽

Kyle C. Stamper ◽

An Q. Dinh ◽

...

Keyword(s):

Body Weight ◽

Bloodstream Infection ◽

Clinical Isolate ◽

Rat Model ◽

Enterococcus Faecium ◽

Dose Regimen ◽

Clinical Isolates ◽

Content Type ◽

Inoculum Effect ◽

Derivatives Of

ABSTRACT Enterococcus faecium isolates that harbor LiaFSR substitutions but are phenotypically susceptible to daptomycin (DAP) by current breakpoints are problematic, since predisposition to resistance may lead to therapeutic failure. Using a simulated endocardial vegetation (SEV) pharmacokinetic/pharmacodynamic (PK/PD) model, we investigated DAP regimens (6, 8, and 10 mg/kg of body weight/day) as monotherapy and in combination with ampicillin (AMP), ceftaroline (CPT), or ertapenem (ERT) against E. faecium HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively). Of interest, the efficacy of DAP monotherapy, at any dose regimen, was dependent on the size of the inoculum. At an inoculum of ∼109 CFU/g, DAP doses of 6 to 8 mg/kg/day were not effective and led to significant regrowth with emergence of resistant derivatives. In contrast, at an inoculum of ∼107 CFU/g, marked reductions in bacterial counts were observed with DAP at 6 mg/kg/day, with no resistance. The inoculum effect was confirmed in a rat model using humanized DAP exposures. Combinations of DAP with AMP, CPT, or ERT demonstrated enhanced eradication and reduced potential for resistance, allowing de-escalation of the DAP dose. Persistence of the LiaRS substitutions was identified in DAP-resistant isolates recovered from the SEV model and in DAP-resistant derivatives of an initially DAP-susceptible clinical isolate of E. faecium (HOU668) harboring LiaSR substitutions that was recovered from a patient with a recurrent bloodstream infection. Our results provide novel data for the use of DAP monotherapy and combinations for recalcitrant E. faecium infections and pave the way for testing these approaches in humans.

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1798. Phenotypic and Genotypic Impact of Antibiotic Stewardship Intervention on Daptomycin-Nonsusceptible Enterococcus faecium (DNSE) Clinical Isolates

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1454 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S509-S510

Author(s):

Abhay Dhand ◽

Leslie Lee ◽

Nicholas Feola ◽

Donald Chen ◽

Nevenka Dimitrova ◽

...

Keyword(s):

Enterococcus Faecium ◽

Antibiotic Stewardship ◽

Clinical Isolates

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Detection of a cfr(B) Variant in German Enterococcus faecium Clinical Isolates and the Impact on Linezolid Resistance in Enterococcus spp.

PLoS ONE ◽

10.1371/journal.pone.0167042 ◽

2016 ◽

Vol 11 (11) ◽

pp. e0167042 ◽

Cited By ~ 25

Author(s):

Jennifer K. Bender ◽

Carola Fleige ◽

Ingo Klare ◽

Stefan Fiedler ◽

Alexander Mischnik ◽

...

Keyword(s):

Enterococcus Faecium ◽

Clinical Isolates ◽

Linezolid Resistance ◽

Enterococcus Spp ◽

The Impact

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Diversity of Tn1546 in vanA -positive Enterococcus faecium clinical isolates with VanA, VanB, and VanD phenotypes and susceptibility to vancomycin

Journal of Applied Microbiology ◽

10.1111/jam.12300 ◽

2013 ◽

Vol 115 (4) ◽

pp. 969-976 ◽

Cited By ~ 2

Author(s):

J.O. Cha ◽

J.I. Yoo ◽

H.K. Kim ◽

H.S. Kim ◽

J.S. Yoo ◽

...

Keyword(s):

Enterococcus Faecium ◽

Clinical Isolates

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Construction of Improved Temperature-Sensitive and Mobilizable Vectors and Their Use for Constructing Mutations in the Adhesin-Encoding acm Gene of Poorly Transformable Clinical Enterococcus faecium Strains

Applied and Environmental Microbiology ◽

10.1128/aem.72.1.334-345.2006 ◽

2006 ◽

Vol 72 (1) ◽

pp. 334-345 ◽

Cited By ~ 48

Author(s):

Sreedhar R. Nallapareddy ◽

Kavindra V. Singh ◽

Barbara E. Murray

Keyword(s):

Enterococcus Faecium ◽

Deletion Mutant ◽

Clinical Isolates ◽

Marker Genes ◽

Temperature Sensitive ◽

Gram Positive ◽

Transcriptional Terminator ◽

Double Crossover ◽

Allelic Exchange ◽

Allelic Replacement

ABSTRACT Inactivation by allelic exchange in clinical isolates of the emerging nosocomial pathogen Enterococcus faecium has been hindered by lack of efficient tools, and, in this study, transformation of clinical isolates was found to be particularly problematic. For this reason, a vector for allelic replacement (pTEX5500ts) was constructed that includes (i) the pWV01-based gram-positive repAts replication region, which is known to confer a high degree of temperature intolerance, (ii) Escherichia coli oriR from pUC18, (iii) two extended multiple-cloning sites located upstream and downstream of one of the marker genes for efficient cloning of flanking regions for double-crossover mutagenesis, (iv) transcriptional terminator sites to terminate undesired readthrough, and (v) a synthetic extended promoter region containing the cat gene for allelic exchange and a high-level gentamicin resistance gene, aph(2′′)-Id, to distinguish double-crossover recombination, both of which are functional in gram-positive and gram-negative backgrounds. To demonstrate the functionality of this vector, the vector was used to construct an acm (encoding an adhesin to collagen from E. faecium) deletion mutant of a poorly transformable multidrug-resistant E. faecium endocarditis isolate, TX0082. The acm-deleted strain, TX6051 (TX0082Δacm), was shown to lack Acm on its surface, which resulted in the abolishment of the collagen adherence phenotype observed in TX0082. A mobilizable derivative (pTEX5501ts) that contains oriT of Tn916 to facilitate conjugative transfer from the transformable E. faecalis strain JH2Sm::Tn916 to E. faecium was also constructed. Using this vector, the acm gene of a nonelectroporable E. faecium wound isolate was successfully interrupted. Thus, pTEX5500ts and its mobilizable derivative demonstrated their roles as important tools by helping to create the first reported allelic replacement in E. faecium; the constructed this acm deletion mutant will be useful for assessing the role of acm in E. faecium pathogenesis using animal models.

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