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Azole Resistance in Aspergillus fumigatus. The first 2-year's Data from the Danish National Surveillance Study, 2018-2020

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  • Malene Risum
  • Rasmus Krøger Hare
  • Jan Berg Gertsen
  • Lise Kristensen
  • Flemming Schønning Rosenvinge
  • Sofia Sulim
  • Nissrine Abou-Chakra
  • Jette Bangsborg
  • Bent Løwe Røder
  • Ea Sofie Marmolin
  • Karen Marie Thyssen Astvad
  • Michael Pedersen
  • Esad Dzajic
  • Steen Lomborg Andersen
  • Maiken Cavling Arendrup
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BACKGROUND: Azole resistance complicates treatment of patients with invasive aspergillosis with an increased mortality. Azole resistance in Aspergillus fumigatus is a growing problem and associated with human and environmental azole use. Denmark has a considerable and highly efficient agricultural sector. Following reports on environmental azole resistance in A. fumigatus from Danish patients, the ministry of health requested a prospective national surveillance of azole-resistant A. fumigatus and particularly that of environmental origin.

OBJECTIVES: To present the data from the first 2 years of the surveillance programme.

METHODS: Unique isolates regarded as clinically relevant and any A. fumigatus isolated on a preferred weekday (background samples) were included. EUCAST susceptibility testing was performed and azole-resistant isolates underwent cyp51A gene sequencing.

RESULTS: The azole resistance prevalence was 6.1% (66/1083) at patient level. The TR34 /L98H prevalence was 3.6% (39/1083) and included the variants TR34 /L98H, TR34 3 /L98H and TR34 /L98H/S297T/F495I. Resistance caused by other Cyp51A variants accounted for 1.3% (14/1083) and included G54R, P216S, F219L, G54W, M220I, M220K, M220R, G432S, G448S and Y121F alterations. Non-Cyp51A-mediated resistance accounted for 1.2% (13/1083). Proportionally, TR34 /L98H, other Cyp51A variants and non-Cyp51A-mediated resistance accounted for 59.1% (39/66), 21.2% (14/66) and 19.7% (13/66), respectively, of all resistance. Azole resistance was detected in all five regions in Denmark, and TR34 /L98H specifically, in four of five regions during the surveillance period.

CONCLUSION: The azole resistance prevalence does not lead to a change in the initial treatment of aspergillosis at this point, but causes concern and leads to therapeutic challenges in the affected patients.

Original languageEnglish
Article number13426
JournalMycoses
Volume65
Issue number4
Pages (from-to)419-428
Number of pages10
ISSN0933-7407
DOIs
Publication statusPublished - Apr 2022

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