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Azole-resistant central nervous system aspergillosis

Jan W M van der Linden1, Rogier R Jansen, Dorine Bresters

  • 1Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|March 11, 2009
PubMed

Insights

Azole-resistant Aspergillus fumigatus caused central nervous system aspergillosis in three patients. Despite treatment with combination or polyene therapy, all patients unfortunately died, highlighting challenges in managing this resistant fungal infection.

Area of Science:

  • Medical Mycology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Central nervous system aspergillosis is a severe opportunistic infection.
  • Emergence of azole resistance in Aspergillus fumigatus poses a significant clinical challenge.
  • Specific genetic mutations, including L98H and promoter region alterations, are linked to azole resistance.

Observation:

  • Three cases of central nervous system aspergillosis caused by azole-resistant Aspergillus fumigatus are presented.
  • The identified resistance mechanism involved a leucine substitution for histidine at codon 98 (L98H) and a 34-base pair tandem repeat in the promoter region.
  • Patients received combination antifungal therapy or polyene-based treatments.

Findings:

  • All three patients with central nervous system aspergillosis due to azole-resistant Aspergillus fumigatus experienced fatal outcomes.
  • Treatment with standard or alternative antifungal regimens proved ineffective.
  • The study underscores the limited therapeutic options for invasive aspergillosis caused by resistant strains.

Implications:

  • Azole resistance in Aspergillus fumigatus significantly complicates the management of invasive aspergillosis.
  • Delayed initiation of effective therapy is a major consequence of azole resistance.
  • There is a critical need for the development of novel antifungal agents and improved diagnostic strategies to combat resistant fungal infections.

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