Evidence map›Paper›PMID 39424629›Full record

ArticleNature communications2024

Molecular mechanisms of re-emerging chloramphenicol susceptibility in extended-spectrum beta-lactamase-producing Enterobacterales.

Fabrice E Graf, Richard N Goodman, Sarah Gallichan, Sally Forrest, Esther Picton-Barlow, Alice J Fraser, Minh-Duy Phan, Madalitso Mphasa, Alasdair T M Hubbard, Patrick Musicha and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Pangenome analysis ofAntimicrobial agents and chemotherapy · 2026
    Article
  2. Microbiology spectrum · 2026
    Article
  3. A Pilot Study ofDiagnostics (Basel, Switzerland) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Extended-Spectrum β-Lactamase-ProducingAntibiotics (Basel, Switzerland) · 2025
    Article
  9. Third-Generation Cephalosporin-Resistant UropathogenicThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025
    Article
  10. Article
  11. Article
  12. 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

15 authors.

Fabrice E GrafDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK. fabrice.graf@lstmed.ac.uk.ORCID 0000-0003-1132-5348
Richard N GoodmanDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0009-0008-0578-789X
Sarah GallichanDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
Sally ForrestDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
Esther Picton-BarlowDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0009-0002-1189-4751
Alice J FraserDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
Minh-Duy PhanInstitute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.ORCID 0000-0002-3426-1044
Madalitso MphasaMalawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.
Alasdair T M HubbardDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0000-0001-6668-9179
Patrick MusichaMalawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi.
Mark A SchembriInstitute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.ORCID 0000-0003-4863-9260
Adam P RobertsDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0000-0002-0760-3088
Thomas EdwardsDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0000-0003-4058-4461
Joseph M LewisDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0000-0002-3837-5188
Nicholas A FeaseyDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.ORCID 0000-0003-4041-1405

Funding

Medical Research Council MR/W030578/1RCUK | Medical Research Council (MRC) MR/N013514/1Research Councils UK (RCUK) 107136Research Councils UK (RCUK) MR/W030578/1Unilever MA-2021-00523N
6 · The paper itself

Abstract

Infections with Enterobacterales (E) are increasingly difficult to treat due to antimicrobial resistance. After ceftriaxone replaced chloramphenicol (CHL) as empiric therapy for suspected sepsis in Malawi in 2004, extended-spectrum beta-lactamase (ESBL)-E rapidly emerged. Concurrently, resistance to CHL in Escherichia coli and Klebsiella spp. decreased, raising the possibility of CHL re-introduction. However, many phenotypically susceptible isolates still carry CHL acetyltransferase (cat) genes. To understand the molecular mechanisms and stability of this re-emerging CHL susceptibility we use a combination of genomics, phenotypic susceptibility assays, experimental evolution, and functional assays for CAT activity. Here, we show that of 840 Malawian E. coli and Klebsiella spp. isolates, 31% have discordant CHL susceptibility genotype-phenotype, and we select a subset of 42 isolates for in-depth analysis. Stable degradation of cat genes by insertion sequences leads to re-emergence of CHL susceptibility. Our study suggests that CHL could be reintroduced as a reserve agent for critically ill patients with ESBL-E infections in Malawi and similar settings and highlights the ongoing challenges in inferring antimicrobial resistance from sequence data.

Indexed as

Anti-Bacterial Agentsbeta-LactamasesChloramphenicolEscherichia coliKlebsiellaMicrobial Sensitivity TestsChloramphenicol O-AcetyltransferaseGenotypeHumansMalawiAnti-Bacterial Agentsbeta-LactamasesChloramphenicolChloramphenicol O-Acetyltransferase

Identifiers

PMID39424629
PMCPMC11489765

What OpenQuestion holds

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LicenceCC BY
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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.