Evidence map›Paper›PMID 21467016›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2011

High-frequency triazole resistance found In nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease.

David W Denning, Steven Park, Cornelia Lass-Florl, Marcin G Fraczek, Marie Kirwan, Robin Gore, Jaclyn Smith, Ahmed Bueid, Caroline B Moore, Paul Bowyer and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 3 pooled it
16.9field-weighted citation impact, top 1% 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

131 citing papers in PubMed, 3 syntheses or guidelines pooled it, 311 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016
    Guideline
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  6. Azole Resistance inOpen forum infectious diseases · 2026
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  7. Evaluation of anAntimicrobial agents and chemotherapy · 2026
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  11. Invasive Aspergillosis with Secondary Bacterial Infection withJournal of pharmacy & bioallied sciences · 2025
    Article
  12. Loss of theMicrobiology spectrum · 2025
    Article
  13. Review
  14. Observational
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

71 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

11 authors at 5 institutions in 2 countries.

David W DenningNational Aspergillosis Centre, University of Manchester, Manchester, UK. ddenning@manchester.ac.uk
Steven Park
Cornelia Lass-Florl
Marcin G Fraczek
Marie Kirwan
Robin Gore
Jaclyn Smith
Ahmed Bueid
Caroline B Moore
Paul Bowyer
David S Perlin
University of Manchester · GBRutgers New Jersey Medical SchoolInnsbruck Medical University · ATManchester Academic Health Science Centre · GBNational Computing Centre (United Kingdom) · GB

Funding

Rapid and Expandable Nucleic Acid Platform to Detect Bloodstream InfectionsU01AI066561 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI PERLIN, DAVID S · 2005 to 2009
$3.5M
NIAID NIH HHS AI066561NIAID NIH HHS U01 AI066561Wellcome Trust
6 · The paper itself

Abstract

backgroundOral triazole therapy is well established for the treatment of invasive (IPA), allergic (ABPA), and chronic pulmonary (CPA) aspergillosis, and is often long-term. Triazole resistance rates are rising internationally. Microbiological diagnosis of aspergillosis is limited by poor culture yield, leading to uncertainty about the frequency of triazole resistance.

methodsUsing an ultrasensitive real-time polymerase chain reaction (PCR) assay for Aspergillus spp., we assessed respiratory fungal load in bronchoalveolar lavage (BAL) and sputum specimens. In a subset of PCR-positive, culture negative samples, we further amplified the CYP51A gene to detect key single-nucleotide polymorphisms (SNPs) associated with triazole resistance.

resultsAspergillus DNA was detected in BAL from normal volunteers (4/11, 36.4%) and patients with culture or microscopy confirmed IPA (21/22, 95%). Aspergillus DNA was detected in sputum in 15 of 19 (78.9%) and 30 of 42 (71.4%) patients with ABPA and CPA, compared with 0% and 16.7% by culture, respectively. In culture-negative, PCR-positive samples, we detected triazole-resistance mutations (L98H with tandem repeat [TR] and M220) within the drug target CYP51A in 55.1% of samples. Six of 8 (75%) of those with ABPA and 12 of 24 (50%) with CPA had resistance markers present, some without prior triazole treatment, and in most despite adequate plasma drug concentrations around the time of sampling.

conclusionsThe very low organism burdens of fungi causing infection have previously prevented direct culture and detection of antifungal resistance in clinical samples. These findings have major implications for the sustainability of triazoles for human antifungal therapy.

Indexed as

Drug Resistance, FungalAntifungal AgentsAspergillosis, Allergic BronchopulmonaryAspergillus fumigatusBronchoalveolar Lavage FluidChronic DiseaseCulture MediaDNA, FungalHumansInvasive Pulmonary AspergillosisLungMutationPolymerase Chain ReactionPulmonary AspergillosisSputumTriazolesAntifungal AgentsCulture MediaDNA, FungalTriazoles

Identifiers

PMID21467016
PMCPMC3106268
OpenAlexW2120323783

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.