Triazole resistance in Aspergillus fumigatus isolates from patients with cystic fibrosis in Italy

J Cyst Fibros. 2017 Jan;16(1):64-69. doi: 10.1016/j.jcf.2016.06.006. Epub 2016 Jun 26.

Abstract

Background: Aspergillus fumigatus is frequently recovered from respiratory secretions of cystic fibrosis (CF) patients. Azole resistance has been increasingly reported.

Objectives: To assess the prevalence of azole resistance in A. fumigatus isolates from patients followed by two CF centers of northern Italy.

Methods: 423 isolates (220 patients) were screened for azole resistance. Resistance was confirmed with the EUCAST method and cyp51A gene sequencing. Microsatellite genotyping was performed and results were compared with those of environmental resistant isolates.

Results: No resistance was detected in one center, while 8.2% of the patients of the other center harbored resistant isolates. The TR34/L98H alteration in the cyp51A gene, present in seven cases, resulted associated with poor in-vitro activity of all tested azoles.

Conclusions: The environmental origin of the resistance seems to be probable since azole resistance was found also in naïve patients and an identical microsatellite genotype in clinical and environmental isolates was observed.

Keywords: Aspergillus fumigatus; Azole resistance; Cystic fibrosis; Italy.

MeSH terms

  • Adolescent
  • Adult
  • Antifungal Agents / pharmacology
  • Aspergillus fumigatus* / drug effects
  • Aspergillus fumigatus* / genetics
  • Aspergillus fumigatus* / isolation & purification
  • Child
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / epidemiology
  • Cystic Fibrosis* / microbiology
  • Cytochrome P-450 Enzyme System / genetics*
  • Drug Resistance, Fungal / genetics
  • Environment
  • Female
  • Fungal Proteins / genetics*
  • Humans
  • Italy / epidemiology
  • Male
  • Microbial Sensitivity Tests / methods
  • Point Mutation
  • Prevalence
  • Pulmonary Aspergillosis* / diagnosis
  • Pulmonary Aspergillosis* / drug therapy
  • Pulmonary Aspergillosis* / epidemiology
  • Pulmonary Aspergillosis* / etiology
  • Triazoles / pharmacology*

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Triazoles
  • Cytochrome P-450 Enzyme System
  • cytochrome P-450 CYP51A, Aspergillus