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The Current Status of Drug-resistant Aspergillus

Masato Tashiro1, Koichi Izumikawa

  • 1Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences.

Medical Mycology Journal
|September 2, 2016
PubMed

Insights

Azole-resistant Aspergillus fumigatus, a cause of serious infections, has been identified in Japan. This resistance, linked to CYP51A mutations, poses treatment challenges, particularly for chronic aspergillosis patients.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance

Background:

  • Aspergillosis presents a high mortality risk.
  • Limited oral anti-aspergillus drug options exist, with only itraconazole (ITCZ) and voriconazole (VRCZ) available in Japan.
  • Emergence of azole-resistant Aspergillus strains globally necessitates local surveillance.

Purpose of the Study:

  • To investigate the presence and characteristics of azole-resistant Aspergillus fumigatus in Japanese clinical settings.
  • To understand the genetic mechanisms underlying azole resistance in Aspergillus.

Main Methods:

  • Detection and identification of Aspergillus isolates from clinical samples.
  • Antifungal susceptibility testing to determine azole resistance.
  • Molecular analysis of the CYP51A gene to identify resistance-conferring mutations.

Main Results:

  • Azole-resistant Aspergillus fumigatus strains were identified in Japanese clinical settings.
  • Resistance was associated with mutations in the target protein, CYP51A.
  • Long-term itraconazole treatment was found to induce specific CYP51A mutations (G54 substitution), leading to itraconazole resistance.

Conclusions:

  • Azole resistance in Aspergillus fumigatus is a growing concern in Japan, mirroring global trends.
  • Mutations in CYP51A are a key mechanism for azole resistance.
  • Continued monitoring for resistant isolates is crucial for managing aspergillosis, especially chronic cases potentially untreatable with oral azoles.

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