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 Dec;27(12):1774-1778. doi: 10.1016/j.jiac.2021.08.024. Epub 2021 Sep 10.

Abstract

Background: Prevalence reports of triazole-resistance in Aspergillus fumigatus differ between countries and centers and may likewise vary over time. Continuous local surveillance programs to establish the evolving epidemiology of triazole-resistance in A. fumigatus are crucial to guide therapeutic recommendations. Here, we determined the prevalence of triazole-resistance in A. fumigatus complex culture-positive patients at the tertiary care center University Hospitals Leuven in Belgium in clinical isolates from 2016 to 2020.

Methods: All A. fumigatus complex isolates cultured from UZ Leuven patients between 2016 and 2020 were screened for triazole-resistance. Confirmation of resistance to voriconazole, posaconazole and itraconazole was performed with the European Committee for Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. Mutations in the cyp51A gene in triazole-resistant isolates were determined by sequencing. Patients were classified as susceptible or resistant cases based on their isolate's susceptibility phenotype.

Results: We screened 2494 A. fumigatus complex isolates from 1600 patients (320 ± 38 [SD] patients per year). The prevalence of triazole-resistance in patients was 8.3% (28/337), 6.7% (26/386), 7.0% (21/301), 7.1% (21/294) and 7.4% (21/282) in 2016, 2017, 2018, 2019 and 2020 respectively, with an overall triazole-resistance prevalence of 7.1% (85/1192; 95% CI 6.6-7.7%). The TR34/L98H mutation was the most prevalent (83.0%, 78/94) with most isolates displaying resistance to all triazole antifungals tested (94.8%, 74/78).

Conclusion: The prevalence of triazole-resistance in A. fumigatus has remained stable from 2016 to 2020 in our center ranging between 6.7 and 8.3%, with an overall five-year prevalence of 7.1%. The environmentally associated cyp51A gene mutations were most prevalent amongst triazole-resistant isolates and conferred resistance to all antifungals tested in 73% of the isolates.

Keywords: Aspergillus fumigatus; Belgium; Epidemiology; Surveillance; Triazole-resistance.

MeSH terms

  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Aspergillosis* / drug therapy
  • Aspergillosis* / epidemiology
  • Aspergillus fumigatus* / genetics
  • Belgium / epidemiology
  • Cytochrome P-450 Enzyme System
  • Drug Resistance, Fungal / genetics
  • Fungal Proteins / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Prevalence
  • Tertiary Care Centers
  • Triazoles / pharmacology
  • Triazoles / therapeutic use

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Triazoles
  • Cytochrome P-450 Enzyme System