Evidence map›Paper›PMID 27600049›Full record

ArticleAntimicrobial agents and chemotherapy2016

Genomic Characterization of Colistin Heteroresistance in Klebsiella pneumoniae during a Nosocomial Outbreak.

Teysir Halaby, Emre Kucukkose, Axel B Janssen, Malbert R C Rogers, Dennis J Doorduijn, Adri G M van der Zanden, Nashwan Al Naiemi, Christina M J E Vandenbroucke-Grauls, Willem van Schaik

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
–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

57 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Global prevalence of mutation in theFrontiers in microbiology · 2024
    Pooled it
  3. Article
  4. Article
  5. Polymyxin heteroresistance inJournal of medical microbiology · 2026
    Article
  6. Article
  7. An Investigation of Colistin Heteroresistance inBioMed research international · 2026
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Detection of Colistin Heteroresistance in Carbapenem-ResistantInternational journal of microbiology · 2025
    Article
  13. Article
  14. Theoretical considerations and empirical predictions of the pharmaco- and population dynamics of heteroresistance.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. Heteroresistance to Colistin in Clinical Isolates ofAntibiotics (Basel, Switzerland) · 2023
    Article
  19. Review
  20. Characterization of Carbapenemase-ProducingAntibiotics (Basel, Switzerland) · 2022
    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

9 authors.

Teysir HalabyLaboratory for Medical Microbiology and Public Health, Hengelo, The Netherlands t.halaby@labmicta.nl.
Emre KucukkoseLaboratory for Medical Microbiology and Public Health, Hengelo, The Netherlands.
Axel B JanssenDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Malbert R C RogersDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Dennis J DoorduijnDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Adri G M van der ZandenLaboratory for Medical Microbiology and Public Health, Hengelo, The Netherlands.
Nashwan Al NaiemiLaboratory for Medical Microbiology and Public Health, Hengelo, The Netherlands.
Christina M J E Vandenbroucke-GraulsDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
Willem van SchaikDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Klebsiella pneumoniae is emerging as an important nosocomial pathogen due to its rapidly increasing multidrug resistance, which has led to a renewed interest in polymyxin antibiotics, such as colistin, as antibiotics of last resort. However, heteroresistance (i.e., the presence of a subpopulation of resistant bacteria in an otherwise susceptible culture) may hamper the effectiveness of colistin treatment in patients. In a previous study, we showed that colistin resistance among extended-spectrum-beta-lactamase (ESBL)-producing K. pneumoniae isolates emerged after the introduction of selective digestive tract decontamination (SDD) in an intensive care unit (ICU). In this study, we investigated heteroresistance to colistin among ESBL-producing K. pneumoniae isolates by using population analysis profiles (PAPs). We used whole-genome sequencing (WGS) to identify the mutations that were associated with the emergence of colistin resistance in these K. pneumoniae isolates. We found five heteroresistant subpopulations, with colistin MICs ranging from 8 to 64 mg/liter, which were derived from five clonally related, colistin-susceptible clinical isolates. WGS revealed the presence of mutations in the lpxM, mgrB, phoQ, and yciM genes in colistin-resistant K. pneumoniae isolates. In two strains, mgrB was inactivated by an IS3-like or ISKpn14 insertion sequence element. Complementation in trans with the wild-type mgrB gene resulted in these strains reverting to colistin susceptibility. The MICs for colistin-susceptible strains increased 2- to 4-fold in the presence of the mutated phoQ, lpxM, and yciM alleles. In conclusion, the present study indicates that heteroresistant K. pneumoniae subpopulations may be selected for upon exposure to colistin. Mutations in mgrB and phoQ have previously been associated with colistin resistance, but we provide experimental evidence for roles of mutations in the yciM and lpxM genes in the emergence of colistin resistance in K. pneumoniae.

Indexed as

Anti-Bacterial AgentsBacterial Proteinsbeta-LactamasesColistinCross InfectionDisease OutbreaksDrug Resistance, BacterialGenome, BacterialHumansKlebsiella InfectionsKlebsiella pneumoniaeMicrobial Sensitivity TestsMutationPhylogenyPolymorphism, Single NucleotideAnti-Bacterial AgentsBacterial Proteinsbeta-LactamasesColistinPhoQ protein, Bacteria

Identifiers

PMID27600049
PMCPMC5075093

What OpenQuestion holds

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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.