Evidence map›Paper›PMID 33876817›Full record

ArticleThe Journal of antimicrobial chemotherapy2021

Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile.

Ilse M Boekhoud, Igor Sidorov, Sam Nooij, Céline Harmanus, Ingrid M J G Bos-Sanders, Virginie Viprey, William Spittal, Emma Clark, Kerrie Davies, Jane Freeman and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
  2. Clostridioides difficile pathogenesis and control.Nature reviews. Microbiology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Newly emerging metronidazole-resistantEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2025
    Article
  10. Article
  11. Article
  12. Pathogens (Basel, Switzerland) · 2024
    Review
  13. Article
  14. European Practice for CDI Treatment.Advances in experimental medicine and biology · 2024
    Article
  15. Article
  16. Article
  17. Antibiotic Resistances of Clostridioides difficile.Advances in experimental medicine and biology · 2024
    Article
  18. Antimicrobial Resistance ofInfection and drug resistance · 2024
    Article
  19. Article
  20. Surveillance of Clostridioides difficile Antimicrobial Resistance in the United States.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    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

13 authors at 2 institutions in 3 countries.

Ilse M BoekhoudDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Igor SidorovDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Sam NooijDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Céline HarmanusDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Ingrid M J G Bos-SandersDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Virginie VipreyHealthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK.
William SpittalHealthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK.
Emma ClarkHealthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK.
Kerrie DaviesHealthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK.
Jane FreemanHealthcare Associated Infection Research Group, School of Medicine, University of Leeds, Leeds, UK.
Ed J KuijperDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Wiep Klaas SmitsDepartment of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-7409-2847
COMBACTE-CDI Consortium
Leiden University Medical Center · NLUniversity of Leeds · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUntil recently, metronidazole was the first-line treatment for Clostridioides difficile infection and it is still commonly used. Though resistance has been reported due to the plasmid pCD-METRO, this does not explain all cases.

objectivesTo identify factors that contribute to plasmid-independent metronidazole resistance of C. difficile.

methodsHere, we investigate resistance to metronidazole in a collection of clinical isolates of C. difficile using a combination of antimicrobial susceptibility testing on different solid agar media and WGS of selected isolates.

resultsWe find that nearly all isolates demonstrate a haem-dependent increase in the MIC of metronidazole, which in some cases leads to isolates qualifying as resistant (MIC >2 mg/L). Moreover, we find an SNP in the haem-responsive gene hsmA, which defines a metronidazole-resistant lineage of PCR ribotype 010/MLST ST15 isolates that also includes pCD-METRO-containing strains.

conclusionsOur data demonstrate that haem is crucial for medium-dependent metronidazole resistance in C. difficile.

Indexed as

Clostridioides difficileClostridium InfectionsAnti-Bacterial AgentsClostridioidesHemeHumansMetronidazoleMicrobial Sensitivity TestsMultilocus Sequence TypingRibotypingAnti-Bacterial AgentsHemeMetronidazole

Identifiers

PMID33876817
PMCPMC8212768
OpenAlexW3155929353

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.