1887
  1. Home
  2. Eurosurveillance
  3. Volume 30, Issue 18, 08/May/2025
  4. Article
Surveillance Open Access
Like 0
Download

SDG 3: Antimicrobial resistance

Abstract

Background

Dutch national treatment guidelines for fungal infections have been adapted based on surveillance findings of triazole resistance rates >10% in species isolates. In Belgium, nationwide resistance data have not been collected since 2011.

Aim

Our objective was to evaluate changes in antifungal susceptibility among species isolates from patients with invasive aspergillosis.

Methods

Laboratories across Belgium were invited to send all clinically relevant species isolates from patients diagnosed with invasive aspergillosis, collected between April 2022 and March 2023, to the National Reference Centre for Mycosis at UZ Leuven for identification and antifungal susceptibility testing.

Results

Overall, 29 clinical laboratories contributed 309 isolates from 297 patients. Median patient age was 66 years (range: 6 months–96 years). Among isolates, 61% (189/309) were from male patients. At species level, isolates predominated (278/309, 90%), with a 9.7% (27/278) triazole resistance rate, compared to the 4.6% rate found in 2011. Of 27 resistant isolates, successful sequencing of 26 showed 20 with the TR/L98H resistance mechanism. Across the country, local triazole resistance rates varied. Among provinces in the Flanders region, Antwerp had the highest resistance rate (15.4%: 10/65; p = 0.082), Flemish Brabant (6/48) also had a rate >10%, while Limburg (2/46) had the lowest rate.

Conclusions

Geographical differences in triazole resistance rates stress the importance of implementing broad prospective surveillance initiatives, not limited to one region or one hospital. In Belgium, triazole resistance rates have doubled over 10 years, nearly attaining the 10% threshold, warranting re-evaluation of local empirical antifungal treatment regimen decisions.

© Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2025.30.18.2400559
2025-05-08
2025-05-08
/content/10.2807/1560-7917.ES.2025.30.18.2400559
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/30/18/eurosurv-30-18-1.html?itemId=/content/10.2807/1560-7917.ES.2025.30.18.2400559&mimeType=html&fmt=ahah

References

  1. Denning DW. Global incidence and mortality of severe fungal disease. Lancet Infect Dis. 2024;24(7):e428-38.  https://doi.org/10.1016/S1473-3099(23)00692-8  PMID: 38224705 
  2. Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-60.  https://doi.org/10.1093/cid/ciw326  PMID: 27365388 
  3. Snelders E, Camps SMT, Karawajczyk A, Schaftenaar G, Kema GHJ, van der Lee HA, et al. Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatus. PLoS One. 2012;7(3):e31801.  https://doi.org/10.1371/journal.pone.0031801  PMID: 22396740 
  4. Verweij PE, Arendrup MC, Alastruey-Izquierdo A, Gold JAW, Lockhart SR, Chiller T, et al. Dual use of antifungals in medicine and agriculture: How do we help prevent resistance developing in human pathogens? Drug Resist Updat. 2022;65:100885.  https://doi.org/10.1016/j.drup.2022.100885  PMID: 36283187 
  5. Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, et al. Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol. 2022;20(9):557-71.  https://doi.org/10.1038/s41579-022-00720-1  PMID: 35352028 
  6. Debergh H, Castelain P, Goens K, Lefevere P, Claessens J, De Vits E, et al. Detection of pan-azole resistant Aspergillus fumigatus in horticulture and a composting facility in Belgium. Med Mycol. 2024;62(7):myae055.  https://doi.org/10.1093/mmy/myae055  PMID: 38769604 
  7. Resendiz-Sharpe A, Merckx R, Verweij PE, Maertens J, Lagrou K. Stable prevalence of triazole-resistance in Aspergillus fumigatus complex clinical isolates in a Belgian tertiary care center from 2016 to 2020. J Infect Chemother. 2021;27(12):1774-8.  https://doi.org/10.1016/j.jiac.2021.08.024  PMID: 34518094 
  8. Lestrade PPA, Meis JF, Melchers WJG, Verweij PE. Triazole resistance in Aspergillus fumigatus: recent insights and challenges for patient management. Clin Microbiol Infect. 2019;25(7):799-806.  https://doi.org/10.1016/j.cmi.2018.11.027  PMID: 30580035 
  9. Verweij PE, Mellado E, Melchers WJG. Multiple-triazole-resistant aspergillosis. N Engl J Med. 2007;356(14):1481-3.  https://doi.org/10.1056/NEJMc061720  PMID: 17409336 
  10. Resendiz Sharpe A, Lagrou K, Meis JF, Chowdhary A, Lockhart SR, Verweij PE, ISHAM/ECMM Aspergillus Resistance Surveillance working group. Triazole resistance surveillance in Aspergillus fumigatus. Med Mycol. 2018;56(suppl_1):S83-92.  https://doi.org/10.1093/mmy/myx144  PMID: 29538741 
  11. Vermeulen E, Maertens J, De Bel A, Nulens E, Boelens J, Surmont I, et al. Nationwide surveillance of azole resistance in Aspergillus diseases. Antimicrob Agents Chemother. 2015;59(8):4569-76.  https://doi.org/10.1128/AAC.00233-15  PMID: 25987612 
  12. Resendiz-Sharpe A, Mercier T, Lestrade PPA, van der Beek MT, von dem Borne PA, Cornelissen JJ, et al. Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients. J Antimicrob Chemother. 2019;74(9):2759-66.  https://doi.org/10.1093/jac/dkz258  PMID: 31236587 
  13. Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24(Suppl 1):e1-38.  https://doi.org/10.1016/j.cmi.2018.01.002  PMID: 29544767 
  14. Verweij PE, Ananda-Rajah M, Andes D, Arendrup MC, Brüggemann RJ, Chowdhary A, et al. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist Updat. 2015;21-22:30-40.  https://doi.org/10.1016/j.drup.2015.08.001  PMID: 26282594 
  15. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the mycosis study group education and research consortium. Clin Infect Dis. 2020;71(6):1367-76.  https://doi.org/10.1093/cid/ciz1008  PMID: 31802125 
  16. Blot SI, Taccone FS, Van den Abeele A-M, Bulpa P, Meersseman W, Brusselaers N, et al. , AspICU Study Investigators. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2012;186(1):56-64.  https://doi.org/10.1164/rccm.201111-1978OC  PMID: 22517788 
  17. Verweij PE, Rijnders BJA, Brüggemann RJM, Azoulay E, Bassetti M, Blot S, et al. Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion. Intensive Care Med. 2020;46(8):1524-35.  https://doi.org/10.1007/s00134-020-06091-6  PMID: 32572532 
  18. Koehler P, Bassetti M, Chakrabarti A, Chen SCA, Colombo AL, Hoenigl M, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2021;21(6):e149-62.  https://doi.org/10.1016/S1473-3099(20)30847-1  PMID: 33333012 
  19. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2023. Available from: https://www.R-project.org/
  20. Snelders E, Karawajczyk A, Schaftenaar G, Verweij PE, Melchers WJG. Azole resistance profile of amino acid changes in Aspergillus fumigatus CYP51A based on protein homology modeling. Antimicrob Agents Chemother. 2010;54(6):2425-30.  https://doi.org/10.1128/AAC.01599-09  PMID: 20385860 
  21. Guinea J. Updated EUCAST clinical breakpoints against Aspergillus, implications for the clinical microbiology laboratory. J Fungi (Basel). 2020;6(4):343.  https://doi.org/10.3390/jof6040343  PMID: 33291313 
  22. Resendiz-Sharpe A, Dewaele K, Merckx R, Bustamante B, Vega-Gomez MC, Rolon M, et al. Triazole-resistance in environmental Aspergillus fumigatus in Latin American and African countries. J Fungi (Basel). 2021;7(4):292.  https://doi.org/10.3390/jof7040292  PMID: 33921497 
  23. Chong GM, van der Beek MT, von dem Borne PA, Boelens J, Steel E, Kampinga GA, et al. PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay® in 201 patients with haematological disease suspected for invasive aspergillosis. J Antimicrob Chemother. 2016;71(12):3528-35.  https://doi.org/10.1093/jac/dkw323  PMID: 27530755 
  24. Lestrade PP, Bentvelsen RG, Schauwvlieghe AFAD, Schalekamp S, van der Velden WJFM, Kuiper EJ, et al. Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study. Clin Infect Dis. 2019;68(9):1463-71.  https://doi.org/10.1093/cid/ciy859  PMID: 30307492 
  25. Dladla M, Gyzenhout M, Marias G, Ghosh S. Azole resistance in Aspergillus fumigatus- comprehensive review. Arch Microbiol. 2024;206(7):305.  https://doi.org/10.1007/s00203-024-04026-z  PMID: 38878211 
  26. Pfaller MA, Carvalhaes CG, Rhomberg PR, Desphande LM, Castanheira M. Trends in the activity of mold-active azole agents against Aspergillus fumigatus clinical isolates with and without cyp51 alterations from Europe and North America (2017-2021). J Clin Microbiol. 2024;62(2):e0114123.  https://doi.org/10.1128/jcm.01141-23  PMID: 38193696 
  27. Huygens S, Dunbar A, Buil JB, Klaassen CHW, Verweij PE, van Dijk K, et al. Clinical impact of polymerase chain reaction-based Aspergillus and azole resistance detection in invasive aspergillosis: A prospective multicentre study. Clin Infect Dis. 2023;77:38-45.  https://doi.org/10.1093/cid/ciad141  PMID: 36905147 
  28. NethMap. 2023: Consumption of antimicrobial agents and antimicrobial resistance among medically important bacteria in the Netherlands. Available from: https://swab.nl/nl/exec/file/download/266 - accessed on 18/06/2024
  29. Advise Health Council from the Netherlands: ‘Resistentie ondermijnt de behandeling van schimmelinfecties’ [Resistance undermines treatment of fungal infections]– Nr. 2024/10, Den Haag, 6 juni 2024.
  30. Arendrup MC, Hare RK, Jørgensen KM, Bollmann UE, Bech TB, Hansen CC, et al. Environmental hot spots and resistance-associated application practices for azole-resistant Aspergillus fumigatus, Denmark, 2020-2023. Emerg Infect Dis. 2024;30(8):1531-41.  https://doi.org/10.3201/eid3008.240096  PMID: 38935978 
  31. Chowdhary A, Kathuria S, Xu J, Meis JF. Emergence of azole-resistant aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health. PLoS Pathog. 2013;9(10):e1003633.  https://doi.org/10.1371/journal.ppat.1003633  PMID: 24204249 
  32. Jørgensen LN, Heick TM. Azole us in agriculture, horticulture, and wood preservation – is it indispensable? Front Cell Infect Microbiol. 2021;11:730297.  https://doi.org/10.3389/fcimb.2021.730297  PMID: 34557427 
  33. Flemish information centre for agriculture and horticulture. [Accessed 21 Jun 2024]. Available from: https://vilt.be/nl
  34. Ministry of Agriculture. news from 2020. [Accessed 20 Mar 2024]. Available from: https://www.agroberichtenbuitenland.nl/actueel/nieuws/2020/03/05/belgie---overzicht-waalse-landbouwsector-2017
Doubling of triazole resistance rates in invasive aspergillosis over a 10-year period, Belgium, 1 April 2022 to 31 March 2023
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Lize+Cuypers&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Cuypers Lize</a>, <a href="/search?value1=Robina+Aerts&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Aerts Robina</a>, <a href="/search?value1=Otto+Van+de+gaer&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Van de gaer Otto</a>, <a href="/search?value1=Lore+Vinken&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Vinken Lore</a>, <a href="/search?value1=Rita+Merckx&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Merckx Rita</a>, <a href="/search?value1=Veerle+Gerils&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Gerils Veerle</a>, <a href="/search?value1=Greetje+Vande+Velde&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Vande Velde Greetje</a>, <a href="/search?value1=Agustin+Res%C3%A9ndiz-Sharpe&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Reséndiz-Sharpe Agustin</a>, <a href="/search?value1=Johan+Maertens&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Maertens Johan</a>, <a href="/search?value1=Katrien+Lagrou&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Lagrou Katrien</a></span>. Doubling of triazole resistance rates in invasive aspergillosis over a 10-year period, Belgium, 1 April 2022 to 31 March 2023. <a href="/content/ecdc">Euro Surveill.</a> 2025;30(18):pii=2400559. <a href="https://doi.org/10.2807/1560-7917.ES.2025.30.18.2400559" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2025.30.18.2400559</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 23 Aug 2024;&nbsp;&nbsp; <span class="generated">Accepted</span>: 11 Dec 2024 </span> </p>
/content/10.2807/1560-7917.ES.2025.30.18.2400559
/content/10.2807/1560-7917.ES.2025.30.18.2400559
Loading

Data & Media loading...

Supplementary data

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error