Evidence map›Paper›PMID 25072733›Full record

ArticlePloS one2014

Incidence of Cyp51 A key mutations in Aspergillus fumigatus-a study on primary clinical samples of immunocompromised patients in the period of 1995-2013.

Birgit Spiess, Patricia Postina, Mark Reinwald, Oliver A Cornely, Axel Hamprecht, Martin Hoenigl, Cornelia Lass-Flörl, Peter-Michael Rath, Jörg Steinmann, Thomas Miethke and 5 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Studies in mycology · 2021
    Review
  6. Review
  7. Article
  8. (New) Methods for Detection ofCurrent fungal infection reports · 2019
    Article
  9. Article
  10. New Insights into the Cyp51 Contribution to Azole Resistance inAntimicrobial agents and chemotherapy · 2019
    Article
  11. Article
  12. Review
  13. Article
  14. Molecular Detection of Azole-ResistantFrontiers in microbiology · 2018
    Review
  15. Performance of Molecular Approaches forFrontiers in microbiology · 2018
    Article
  16. Article
  17. Article
  18. Review
  19. Review
  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

15 authors at 8 institutions in 2 countries.

Birgit SpiessDepartment of Hematology and Oncology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Patricia PostinaDepartment of Hematology and Oncology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Mark ReinwaldDepartment of Hematology and Oncology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Oliver A CornelyDepartment I of Internal Medicine, University Hospital of Cologne, Cologne; Clinical Trials Centre Cologne, ZKS Köln, BMBF 01KN1106, and Centre for Integrated Oncology CIO Köln Bonn, and Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Axel HamprechtInstitute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany.
Martin HoeniglSection of Infectious Diseases and Tropical Medicine & Department of Pulmonology, University Hospital of Internal Medicine, Graz Medical University, Graz, Austria.
Cornelia Lass-FlörlSection of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
Peter-Michael RathInstitute of Medical Microbiology, University Hospital of Essen, Essen, Germany.
Jörg SteinmannInstitute of Medical Microbiology, University Hospital of Essen, Essen, Germany.
Thomas MiethkeInstitute of Medical Microbiology and Hygiene, University Hospital Mannheim, Mannheim, Germany.
Melchior LautenPediatric Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Silke WillDepartment of Hematology and Oncology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Natalia MerkerDepartment of Hematology and Oncology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Wolf-Karsten HofmannDepartment of Hematology and Oncology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Dieter BuchheidtDepartment of Hematology and Oncology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Heidelberg University · DEEssen University Hospital · DEUniversity Hospital Cologne · DEUniversity Hospital Heidelberg · DEInstitute of Medical Microbiology and Hygiene · DEMedical University of Graz · ATUniversität Innsbruck · ATUniversity Hospital Schleswig-Holstein · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As the incidence of azole resistance in Aspergillus fumigatus is rising and the diagnosis of invasive aspergillosis (IA) in immunocompromised patients is rarely based on positive culture yield, we screened our Aspergillus DNA sample collection for the occurrence of azole resistance mediating cyp51 A key mutations. Using two established, a modified and a novel polymerase chain reaction (PCR) assays followed by DNA sequence analysis to detect the most frequent mutations in the A. fumigatus cyp51 A gene conferring azole resistance (TR34 (tandem repeat), L98H and M220 alterations). We analyzed two itraconazole and voriconazole and two multi-azole resistant clinical isolates and screened 181 DNA aliquots derived from clinical samples (blood, bronchoalveolar lavage (BAL), biopsies, cerebrospinal fluid (CSF)) of 155 immunocompromised patients of our Aspergillus DNA sample collection, previously tested positive for Aspergillus DNA and collected between 1995 and 2013. Using a novel PCR assay for the detection of the cyp51 A 46 bp tandem repeat (TR46) directly from clinical samples, we found the alteration in a TR46/Y121F/T289A positive clinical isolate. Fifty stored DNA aliquots from clinical samples were TR46 negative. DNA sequence analysis revealed a single L98H mutation in 2010, two times the L98H alteration combined with TR34 in 2011 and 2012 and a so far unknown N90K mutation in 1998. In addition, four clinical isolates were tested positive for the TR34/L98H combination in the year 2012. We consider our assay of epidemiological relevance to detect A. fumigatus azole resistance in culture-negative clinical samples of immunocompromised patients; a prospective study is ongoing.

Indexed as

Immunocompromised HostMutationAntifungal AgentsAspergillosisAspergillus fumigatusAzolesCytochrome P-450 Enzyme SystemDrug Resistance, FungalFungal ProteinsHumansMicrobial Sensitivity TestsPolymerase Chain ReactionSensitivity and SpecificityAntifungal AgentsAzolescytochrome P-450 CYP51A, AspergillusCytochrome P-450 Enzyme SystemFungal Proteins

Identifiers

PMID25072733
PMCPMC4114486
OpenAlexW2084087805

What OpenQuestion holds

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LicenceCC BY
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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.