Evidence map›Paper›PMID 28579300›Full record

ArticleEBioMedicine2017

Correcting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing.

Selvi C Ersoy, Douglas M Heithoff, Lucien Barnes, Geneva K Tripp, John K House, Jamey D Marth, Jeffrey W Smith, Michael J Mahan

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
154citing papers in PubMed, 2 pooled it
13.3field-weighted citation impact, top 1% 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

154 citing papers in PubMed, 2 syntheses or guidelines pooled it, 217 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Genomic investigation and clinical correlates of theAntimicrobial agents and chemotherapy · 2024
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  6. An Achilles' heel for methicillin-resistantAntimicrobial agents and chemotherapy · 2026
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  11. Two Multidrug-ResistantPathogens (Basel, Switzerland) · 2026
    Article
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  13. Methicillin-resistantAntimicrobial agents and chemotherapy · 2026
    Article
  14. Review
  15. Review
  16. Contrasting pH optima of β-lactamases CTX-M and CMY influenceApplied and environmental microbiology · 2026
    Article
  17. Article
  18. Article
  19. Article
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94 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Selvi C ErsoyDept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Douglas M HeithoffDept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA; Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA.
Lucien BarnesDept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Geneva K TrippDept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
John K HouseUniversity of Sydney, Faculty of Veterinary Science, Camden, New South Wales, Australia.
Jamey D MarthDept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA; Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA; Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA 92037, USA.
Jeffrey W SmithSanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA 92037, USA.
Michael J MahanDept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA; Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA. Electronic address: michael.mahan@lifesci.ucsb.edu.
University of California, Santa Barbara · USCancer Research Center · USDiscovery Institute · USUniversity of Sydney · AU

Funding

Protein Glycosylation in the Coagulopathy and Inflammation of SepsisP01HL131474 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MARTH, JAMEY · 2016 to 2025
$26.2M
Glycoprotein Remodeling in the Vasculopathy and Coagulopathy of SepsisR01HL125352 · NHLBI · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI MARTH, JAMEY, NIZET, VICTOR · 2014 to 2018
$3.6M
NHLBI NIH HHS P01 HL131474NHLBI NIH HHS R01 HL125352
6 · The paper itself

Abstract

The emergence and prevalence of antibiotic-resistant bacteria are an increasing cause of death worldwide, resulting in a global 'call to action' to avoid receding into an era lacking effective antibiotics. Despite the urgency, the healthcare industry still relies on a single in vitro bioassay to determine antibiotic efficacy. This assay fails to incorporate environmental factors normally present during host-pathogen interactions in vivo that significantly impact antibiotic efficacy. Here we report that standard antimicrobial susceptibility testing (AST) failed to detect antibiotics that are in fact effective in vivo; and frequently identified antibiotics that were instead ineffective as further confirmed in mouse models of infection and sepsis. Notably, AST performed in media mimicking host environments succeeded in identifying specific antibiotics that were effective in bacterial clearance and host survival, even though these same antibiotics failed in results using standard test media. Similarly, our revised media further identified antibiotics that were ineffective in vivo despite passing the AST standard for clinical use. Supplementation of AST medium with sodium bicarbonate, an abundant in vivo molecule that stimulates global changes in bacterial structure and gene expression, was found to be an important factor improving the predictive value of AST in the assignment of appropriate therapy. These findings have the potential to improve the means by which antibiotics are developed, tested, and prescribed.

Indexed as

Anti-Infective AgentsBacteriaBacterial Physiological PhenomenaDrug Resistance, MicrobialHost-Pathogen InteractionsHumansMicrobial Sensitivity TestsReproducibility of ResultsAnti-Infective AgentsAntibiotic resistanceAntimicrobial susceptibility testing (AST)Antimicrobial therapyMIC testingMultidrug-resistant pathogens

Identifiers

PMID28579300
PMCPMC5478264
OpenAlexW2618823124

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.