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
  • Bangsborg, Jette Marie
  • Bent Løwe Røder
  • Ea Sofie Marmolin
  • Karen Marie Thyssen Astvad
  • Michael Pedersen
  • Esad Dzajic
  • Steen Lomborg Andersen
  • Arendrup, Maiken Cavling

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, TR343/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.

OriginalsprogEngelsk
BogserieMycoses
Vol/bind65
Udgave nummer4
Sider (fra-til)419-428
Antal sider10
ISSN0933-7407
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
MR: Has received research ‐and travel grants from Gilead. RKH: Has over the past 5 years received travel grants and speaker honoraria from Gilead. JBG: Has over the past 5 years received travel grants and speaker honoraria from Gilead. LK: No conflicts of interest. FSR: No conflicts of interest. SS: No conflicts of interest. NA: No conflicts of interest. JB: No conflicts of interest. BLR: No conflicts of interest. EM: No conflicts of interest. KA: Has received travel grant and speaker honoraria from Gilead.MP: No conflicts of interest. ED: No conflicts of interest. SLA: No conflicts of interest. MCA: has outside the current work, over the past 5 years, received research grants/contract work (paid to the SSI) from Amplyx, Basilea, Cidara, F2G, Gilead, Novabiotics and Scynexis, and speaker honoraria (personal fee) from Astellas, Chiesi, Gilead, MSD, and SEGES. She is the current chairman of the EUCAST‐AFST.

Publisher Copyright:
© 2022 The Authors. Mycoses published by Wiley-VCH GmbH.

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