Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona, Spain

Infection. 2024 Oct;52(5):1651-1656. doi: 10.1007/s15010-024-02236-7. Epub 2024 May 27.

Abstract

Objectives: We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months.

Methods: Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation.

Results: Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles.

Conclusion: We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.

Keywords: Aspergillus fumigatus sensu stricto; Azole-resistant Aspergillus; Hematologic patients; Invasive aspergillosis; TR34/L98H mutation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / therapeutic use
  • Aspergillosis* / drug therapy
  • Aspergillosis* / microbiology
  • Aspergillus fumigatus* / drug effects
  • Aspergillus fumigatus* / genetics
  • Aspergillus fumigatus* / isolation & purification
  • Azoles* / pharmacology
  • Azoles* / therapeutic use
  • Drug Resistance, Fungal* / genetics
  • Female
  • Hematologic Neoplasms / complications
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation*
  • Prospective Studies
  • Spain / epidemiology

Substances

  • Azoles
  • Antifungal Agents