Evidence map›Paper›PMID 21969582›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei.

Narisara Chantratita, Drew A Rholl, Bernice Sim, Vanaporn Wuthiekanun, Direk Limmathurotsakul, Premjit Amornchai, Aunchalee Thanwisai, Hui Hoon Chua, Wen Fong Ooi, Matthew T G Holden and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

73 citing papers in PubMed, 117 citations in OpenAlex.

  1. Case Commentary: When susceptibility is not enough in recurrentAntimicrobial agents and chemotherapy · 2026
    Article
  2. Article
  3. Article
  4. Antimicrobial agents and chemotherapy · 2025
    Article
  5. Genomic insights into ceftazidime resistance inAntimicrobial agents and chemotherapy · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Burkholderia pseudomallei and melioidosis.Nature reviews. Microbiology · 2024
    Review
  11. Article
  12. In Vitro Susceptibility ofJournal of laboratory physicians · 2023
    Article
  13. Article
  14. Antibiotic susceptibility of clinicalAntimicrobial agents and chemotherapy · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Antimicrobial Susceptibility of Western Hemisphere Isolates ofMicrobial drug resistance (Larchmont, N.Y.) · 2021
    Article

13 more citing papers are in PubMed but not listed here.

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

14 authors at 6 institutions in 4 countries.

Narisara ChantratitaDepartment of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Drew A Rholl
Bernice Sim
Vanaporn Wuthiekanun
Direk Limmathurotsakul
Premjit Amornchai
Aunchalee Thanwisai
Hui Hoon Chua
Wen Fong Ooi
Matthew T G Holden
Nicholas P Day
Patrick Tan
Herbert P Schweizer
Sharon J Peacock
Genome Institute of Singapore · SGMahidol Oxford Tropical Medicine Research Unit · THColorado State University · USMahidol University · THUniversity of Oxford · GBWellcome Sanger Institute · GB

Funding

Vascular stabilization as a broad theraprutic platform for biodefenseU54AI065357 · NIAID · COLORADO STATE UNIVERSITY-FORT COLLINS · PI SCHWEIZER, HERBERT P. · 2005 to 2013
$77.5M
NIAID NIH HHS AI065357NIAID NIH HHS U54 AI065357Wellcome Trust 087769/Z/08/
6 · The paper itself

Abstract

Known mechanisms of resistance to β-lactam antibiotics include β-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of β-lactam resistance in the biothreat organism Burkholderia pseudomallei (the cause of melioidosis), associated with treatment failure during prolonged ceftazidime therapy of natural infection. Detailed comparisons of the initial ceftazidime-susceptible infecting isolate and subsequent ceftazidime-resistant variants from six patients led us to identify a common, large-scale genomic loss involving a minimum of 49 genes in all six resistant strains. Mutational analysis of wild-type B. pseudomallei demonstrated that ceftazidime resistance was due to deletion of a gene encoding a penicillin-binding protein 3 (BPSS1219) present within the region of genomic loss. The clinical ceftazidime-resistant variants failed to grow using commonly used laboratory culture media, including commercial blood cultures, rendering the variants almost undetectable in the diagnostic laboratory. Melioidosis is notoriously difficult to cure and clinical treatment failure is common in patients treated with ceftazidime, the drug of first choice across most of Southeast Asia where the majority of cases are reported. The mechanism described here represents an explanation for ceftazidime treatment failure, and may be a frequent but undetected resistance event.

Indexed as

Anti-Bacterial AgentsAsia, SoutheasternBase SequenceBurkholderia pseudomalleiCeftazidimeDNA, BacterialDrug Resistance, BacterialGene DeletionGenes, BacterialHumansMelioidosisPenicillin-Binding ProteinsTreatment FailureAnti-Bacterial AgentsCeftazidimeDNA, BacterialPenicillin-Binding Proteins

Identifiers

PMID21969582
PMCPMC3193241
OpenAlexW2154846135

What OpenQuestion holds

Textmetadata
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.