Evidence map›Paper›PMID 25564565›Full record

ArticleThe Journal of antimicrobial chemotherapy2015

Early agr activation correlates with vancomycin treatment failure in multi-clonotype MRSA endovascular infections.

Wessam Abdelhady, Liang Chen, Arnold S Bayer, Kati Seidl, Michael R Yeaman, Barry N Kreiswirth, Yan Q Xiong

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
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  15. Bicarbonate Resensitization of Methicillin-ResistantAntimicrobial agents and chemotherapy · 2019
    Article
  16. Review
  17. Linezolid and Rifampicin Combination to CombatFrontiers in microbiology · 2019
    Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Wessam AbdelhadyLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Liang ChenPublic Health Research Institute, NJMS-Rutgers University, Newark, NJ, USA.
Arnold S BayerLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Kati SeidlUniversity Hospital Zurich, University of Zurich, Zurich, Switzerland.
Michael R YeamanLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Barry N KreiswirthPublic Health Research Institute, NJMS-Rutgers University, Newark, NJ, USA.
Yan Q XiongLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA David Geffen School of Medicine at UCLA, Los Angeles, CA, USA yxiong@ucla.edu.
Harbor–UCLA Medical Center · USRutgers, The State University of New Jersey · USUniversity of Zurich · CH

Funding

Staphylococcal Adaptations to Platelet Microbicidal ProteinR01AI039108 · NIAID · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI BAYER, ARNOLD S · 1997 to 2016
$5.1M
Early agr Activation is a Key Pathogenic Signature in Persistent MRSA BacteremiaR21AI097657 · NIAID · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI XIONG, YAN Q. · 2012 to 2013
$390k
NIAID NIH HHS R01AI-39108NIAID NIH HHS R21AI097657
6 · The paper itself

Abstract

objectivesPersistent MRSA infections are especially relevant to endovascular infections and correlate with suboptimal outcomes. However, the virulence signatures of Staphylococcus aureus that drive such persistence outcomes are not well defined. In the current study, we investigated correlations between accessory gene regulator (agr) activation and the outcome of vancomycin treatment in an experimental model of infective endocarditis (IE) due to MRSA strains with different agr and clonal complex (CC) types.

methodsTwelve isolates with the four most common MRSA CC and agr types (CC5-agr II, CC8-agr I, CC30-agr III and CC45-agr I) were evaluated for heterogeneous vancomycin-intermediate S. aureus (hVISA), agr function, agrA and RNAIII transcription, agr locus sequences, virulence and response to vancomycin in the IE model.

resultsEarly agr RNAIII activation (beginning at 2 h of growth) in parallel with strong δ-haemolysin production correlated with persistent outcomes in the IE model following vancomycin therapy. Importantly, such treatment failures occurred across the range of CC/agr types studied. In addition, these MRSA strains: (i) were vancomycin susceptible in vitro; (ii) were not hVISA or vancomycin tolerant; and (iii) did not evolve hVISA phenotypes or perturbed δ-haemolysin activity in vivo following vancomycin therapy. Moreover, agr locus sequence analyses revealed no common point mutations that correlated with either temporal RNAIII transcription or vancomycin treatment outcomes, encompassing different CC and agr types.

conclusionsThese data suggest that temporal agr RNAIII activation and agr functional profiles may be useful biomarkers to predict the in vivo persistence of endovascular MRSA infections despite vancomycin therapy.

Indexed as

Transcriptional ActivationAnimalsAnti-Bacterial AgentsBacterial ProteinsDisease Models, AnimalEndocarditisGene Expression ProfilingMethicillin-Resistant Staphylococcus aureusRabbitsSequence Analysis, DNAStaphylococcal InfectionsTrans-ActivatorsTreatment FailureVirulenceAgr protein, Staphylococcus aureusAnti-Bacterial AgentsBacterial ProteinsTrans-Activatorsantibioticsbacteriaresistance

Identifiers

PMID25564565
PMCPMC4398469
OpenAlexW2145997688

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.