Evidence map›Paper›PMID 20404915›Full record

ArticlePloS one2010

Development of azole resistance in Aspergillus fumigatus during azole therapy associated with change in virulence.

Maiken Cavling Arendrup, Eleftheria Mavridou, Klaus Leth Mortensen, Eveline Snelders, Niels Frimodt-Møller, Humara Khan, Willem J G Melchers, Paul E Verweij

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
8.7field-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

80 citing papers in PubMed, 173 citations in OpenAlex.

  1. Climate change and antimicrobial resistance.Nature reviews. Microbiology · 2026
    Review
  2. Article
  3. Azole-ResistantJournal of fungi (Basel, Switzerland) · 2025
    Review
  4. Review
  5. The Influence ofJournal of fungi (Basel, Switzerland) · 2024
    Article
  6. Insights intoJournal of fungi (Basel, Switzerland) · 2024
    Article
  7. Review
  8. Resistance profiling ofEmerging microbes & infections · 2022
    Article
  9. Journal of fungi (Basel, Switzerland) · 2022
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Studies in mycology · 2021
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Structural basis of HapELife science alliance · 2020
    Article
  20. Lysine acetylation as drug target in fungi: an underexplored potential in Aspergillus spp.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2020
    Review

20 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

8 authors at 4 institutions in 2 countries.

Maiken Cavling ArendrupUnit of Mycology and Parasitology, Statens Serum Institut, Copenhagen, Denmark. mad@ssi.dk
Eleftheria Mavridou
Klaus Leth Mortensen
Eveline Snelders
Niels Frimodt-Møller
Humara Khan
Willem J G Melchers
Paul E Verweij
Statens Serum Institut · DKHospital South West Jutland · DKRadboud University Medical Center · NLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Four sequential Aspergillus fumigatus isolates from a patient with chronic granulomatous disease (CGD) eventually failing azole-echinocandin combination therapy were investigated. The first two isolates (1 and 2) were susceptible to antifungal azoles, but increased itraconazole, voriconazole and posaconazole MICs were found for the last two isolates (3 and 4). Microsatellite typing showed that the 4 isolates were isogenic, suggesting that resistance had been acquired during azole treatment of the patient. An immunocompromised mouse model confirmed that the in vitro resistance corresponded with treatment failure. Mice challenged with the resistant isolate 4 failed to respond to posaconazole therapy, while those infected by susceptible isolate 2 responded. Posaconazole-anidulafungin combination therapy was effective in mice challenged with isolate 4. No mutations were found in the Cyp51A gene of the four isolates. However, expression experiments of the Cyp51A showed that the expression was increased in the resistant isolates, compared to the azole-susceptible isolates. The microscopic morphology of the four isolates was similar, but a clear alteration in radial growth and a significantly reduced growth rate of the resistant isolates on solid and in broth medium was observed compared to isolates 1 and 2 and to unrelated wild-type controls. In the mouse model the virulence of isolates 3 and 4 was reduced compared to the susceptible ones and to wild-type controls. For the first time, the acquisition of azole resistance despite azole-echinocandin combination therapy is described in a CGD patient and the resistance demonstrated to be directly associated with significant change of virulence.

Indexed as

Drug Resistance, FungalAnimalsAntifungal AgentsAspergillus fumigatusAzolesDrug Therapy, CombinationGranulomatous Disease, ChronicHumansMiceVirulenceAntifungal AgentsAzoles

Identifiers

PMID20404915
PMCPMC2852403
OpenAlexW1999488124

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.