Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in

A Prigitano1, M C Esposto1, A Grancini2

  • 1Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.

Abstract

Insights

Azole resistance in Aspergillus is a concern, with a 1% prevalence found in immunocompromised patients. This study identified resistance in Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus awamori, highlighting the need for accurate species identification.

Area of Science:

  • Medical Mycology
  • Antifungal Resistance
  • Clinical Microbiology

Background:

  • Azole antifungals are crucial for treating invasive Aspergillus infections, particularly in immunocompromised patients.
  • Emergence of azole resistance in Aspergillus poses a significant threat to patient outcomes.
  • Patients with haematological malignancies and those undergoing stem cell transplantation are at high risk for invasive aspergillosis.

Purpose of the Study:

  • To determine the prevalence of azole resistance in Aspergillus isolates from high-risk patient populations.
  • To investigate the molecular mechanisms underlying azole resistance in these isolates.
  • To assess the epidemiological impact of azole resistance in a multicenter Italian study.

Main Methods:

  • Prospective collection of Aspergillus isolates from surveillance cultures across 18 Italian centers over 28 months.
  • Screening of isolates for resistance to azole antifungals.
  • Identification of mutations in the cyp51A gene and molecular genotyping of resistant strains using microsatellite analysis.

Main Results:

  • A total of 292 Aspergillus isolates were collected from 228 patients, predominantly from the section Fumigati (45.9%).
  • Three isolates exhibited itraconazole resistance: Aspergillus fumigatus sensu stricto, Aspergillus lentulus, and Aspergillus awamori, resulting in an overall azole resistance rate of 1% (3/292).
  • The single azole-resistant Aspergillus fumigatus isolate harbored the TR34/L98H mutation and was genotypically distinct from previously characterized strains.

Conclusions:

  • The study identified a 1% prevalence of azole resistance in Aspergillus isolates from immunocompromised patients, including non-fumigatus species.
  • Accurate species-level identification is critical for effective and timely antifungal therapy.
  • Monitoring local epidemiology and understanding the emergence of cryptic species are essential for managing azole resistance.