Evidence map›Paper›PMID 18644959›Full record

ArticleAntimicrobial agents and chemotherapy2008

Establishing in vitro-in vivo correlations for Aspergillus fumigatus: the challenge of azoles versus echinocandins.

Maiken Cavling Arendrup, Susanne Perkhofer, Susan J Howard, Guillermo Garcia-Effron, Aimanianda Vishukumar, David Perlin, Cornelia Lass-Flörl

Open access · greenAbstract readComparative Study
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Studies in mycology · 2021
    Review
  8. Article
  9. Antimicrobial agents and chemotherapy · 2020
    Article
  10. Article
  11. Article
  12. Article
  13. Detection of Echinocandin-ResistantAntimicrobial agents and chemotherapy · 2019
    Article
  14. Animal Models of Aspergillosis.Comparative medicine · 2018
    Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. 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

7 authors at 5 institutions in 4 countries.

Maiken Cavling ArendrupUnit of Mycology and Parasitology (43/117), Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. mad@ssi.dk
Susanne Perkhofer
Susan J Howard
Guillermo Garcia-Effron
Aimanianda Vishukumar
David Perlin
Cornelia Lass-Flörl
Innsbruck Medical University · ATRutgers New Jersey Medical SchoolInstitut Pasteur · FRStatens Serum Institut · DKUniversity of Manchester · GB

Funding

Mechanism of clinical resistance to echinocandin antifungal drugsR01AI069397 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI PERLIN, DAVID S · 2007 to 2011
$2.0M
NIAID NIH HHS AI069397NIAID NIH HHS R01 AI069397
6 · The paper itself

Abstract

Two clinical isolates of Aspergillus fumigatus, designated AT and DK, were recently obtained from patients failing caspofungin and itraconazole therapy, respectively. The isolates were tested by microdilution for susceptibility to itraconazole, voriconazole, posaconazole, ravuconazole, and caspofungin and by Etest for susceptibility to amphotericin B and caspofungin. Susceptibility testing documented that the DK isolate was azole resistant (itraconazole and posaconazole MICs, >4 microg/ml; voriconazole MIC, 2 microg/ml; ravuconazole MIC, 4 microg/ml), and the resistance was confirmed in a hematogenous mouse model, with mortality and the galactomannan index as the primary and secondary end points. Sequencing of the cyp51A gene revealed the M220K mutation, conferring multiazole resistance. The Etest, but not microdilution, suggested that the AT isolate was resistant to caspofungin (MIC, >32 microg/ml). In the animal model, this isolate showed reduced susceptibility to caspofungin. Sequencing of the FKS1 gene revealed no mutations; the enzyme retained full sensitivity in vitro; and investigation of the polysaccharide composition showed that the beta-(1,3)-glucan proportion was unchanged. However, gene expression profiling by Northern blotting and real-time PCR demonstrated that the FKS gene was expressed at a higher level in the AT isolate than in the susceptible control isolate. To our knowledge, this is the first report to document the presence of multiazole-resistant clinical isolates in Denmark and to demonstrate reduced susceptibility to caspofungin in a clinical A. fumigatus isolate with increased expression of the FKS gene. Further research to determine the prevalence of resistance in A. fumigatus worldwide, and to develop easier and reliable tools for the identification of such isolates in routine laboratories, is warranted.

Indexed as

AdultAnimalsAntifungal AgentsAspergillosisAspergillus fumigatusAzolesBase SequenceCaspofunginCytochrome P-450 Enzyme SystemDisease Models, AnimalDNA, FungalDrug Resistance, Multiple, FungalEchinocandinsFungal ProteinsGenes, FungalGlucosyltransferases1,3-beta-glucan synthaseAntifungal AgentsAzolesCaspofungincytochrome P-450 CYP51A, AspergillusCytochrome P-450 Enzyme SystemDNA, FungalEchinocandinsFungal ProteinsGlucosyltransferasesItraconazoleLipopeptides

Identifiers

PMID18644959
PMCPMC2565905
OpenAlexW1994115447

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.