Evidence map›Paper›PMID 40447858›Full record

Articlenpj antimicrobials and resistance2025

Tazobactam selects for multidrug resistance.

Emma R Holden, Muhammad Yasir, A Keith Turner, Ian G Charles, Mark A Webber

Abstract read
In one paragraph

Article in npj antimicrobials and resistance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Phenotypic Characterization ofAntibiotics (Basel, Switzerland) · 2025
    Article
  3. Article
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

5 authors.

Emma R HoldenQuadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, NR4 7UQ, UK.
Muhammad YasirQuadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, NR4 7UQ, UK.
A Keith TurnerQuadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, NR4 7UQ, UK.
Ian G CharlesQuadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, NR4 7UQ, UK.
Mark A WebberQuadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, NR4 7UQ, UK. Mark.Webber@quadram.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/X011011/1
6 · The paper itself

Abstract

Piperacillin-Tazobactam is a β-lactam/β-lactamase inhibitor combination that is amongst the most prescribed antimicrobials in hospital medicine. Piperacillin is inactivated by many common beta-lactamases, but tazobactam inhibits these, allowing successful treatment. The effect of piperacillin on Gram-negative bacteria has been widely studied, but less attention has been paid to the effects of tazobactam. We used a massive transposon mutagenesis approach (TraDIS-Xpress) to identify genes in Escherichia coli that affect survival when exposed to piperacillin and tazobactam, separately and together. We found significant differences between the two drugs: a striking finding was that multiple efflux pump families and regulators were essential for survival in the presence of tazobactam, but only one efflux system was beneficial for piperacillin. Exposure of Escherichia coli and Klebsiella pneumoniae to piperacillin and/or tazobactam selected for mutants with reduced susceptibility, and tazobactam selected for efflux and cell envelope mutants associated with multidrug resistance. We identified other pathways involved in tazobactam susceptibility, including the shikimate kinase AroK. Genes involved in DNA replication and repair reduced E. coli susceptibility to a combination of piperacillin and tazobactam but were not identified after exposure to either drug alone. Tazobactam can select for mutants with increased efflux activity, and the development of future β-lactamase inhibitors should consider potential selective impacts of both inhibitor and antibiotic.

Identifiers

PMID40447858
PMCPMC12125205

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.