Format

Send to

Choose Destination
See comment in PubMed Commons below
Clin Microbiol Infect. 2016 Jun;22(6):570.e1-9. doi: 10.1016/j.cmi.2016.04.001. Epub 2016 Apr 16.

Azole-resistant Aspergillus fumigatus in Denmark: a laboratory-based study on resistance mechanisms and genotypes.

Author information

  • 1Department of Mycology Unit, Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
  • 2Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, The Netherlands.
  • 3Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, The Netherlands; Department of Medical Microbiology, Radboudumc, Nijmegen, The Netherlands.
  • 4Department of Mycology Unit, Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. Electronic address: maca@ssi.dk.

Abstract

Azole-resistant Aspergillus fumigatus originating from the environment as well as induced during therapy are continuously emerging in Danish clinical settings. We performed a laboratory-based retrospective study (2010-2014) of azole resistance and genetic relationship of A. fumigatus at the national mycology reference laboratory of Denmark. A total of 1162 clinical and 133 environmental A. fumigatus isolates were identified by morphology, thermotolerance and/or β-tubulin sequencing. Screening for azole resistance was carried out using azole agar, and resistant isolates were susceptibility tested by the EUCAST (European Committee on Antimicrobial Susceptibility Testing) E.Def 9.2 reference method and CYP51A sequenced. Genotyping was performed for outbreak investigation and, when appropriate, short tandem repeat Aspergillus fumigatus microsatellite assay. All 133 environmental A. fumigatus isolates were azole susceptible. However, from 2010 to 2014, there was an increasing prevalence of azole resistance (from 1.4 to 6% isolates (p <0.001) and 1.8 to 4% patients (p <0.05)) among the clinical isolates, with the well-known environmental CYP51A variant TR34/L98H responsible for >50% of the azole resistance mechanisms. Among 184 Danish A. fumigatus isolates, 120 unique genotypes were identified and compared to a collection of 1822 international genotypes. Seven (5.8%) Danish genotypes were shared between isolates within Denmark but with different origin, 19 (15.8%) were shared with foreign genotypes, and two (11.8%) of 17 genotypes of isolates carrying the TR34/L98H resistance mechanisms were identical to two Dutch TR34/L98H isolates. Our findings underlines the demand for correct identification and susceptibility testing of clinical mould isolates. Furthermore, although complex, genotyping supported the hypotheses regarding clonal expansion and the potential of a single origin for the TR34/L98H clone.

KEYWORDS:

Aspergillosis; CYP51A; STRAf; TR34/L98H; TR46/Y121F/T289A; azole resistance; genotyping

PMID:
27091095
DOI:
10.1016/j.cmi.2016.04.001
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center