High prevalence of triazole resistance in clinical Aspergillus fumigatus isolates in a specialist cardiothoracic centre

Int J Antimicrob Agents. 2018 Nov;52(5):637-642. doi: 10.1016/j.ijantimicag.2018.08.004. Epub 2018 Aug 10.

Abstract

Objectives: To evaluate the prevalence of triazole-resistant Aspergillus fumigatus and common molecular cyp51A polymorphisms amongst clinical isolates in a specialised cardiothoracic centre in London, UK.

Methods: All A. fumigatus isolates were prospectively analysed from April 2014 to March 2016. Isolates were screened with a four-well VIPcheck™ plate to assess triazole susceptibility. Resistance was confirmed with a standard microbroth dilution method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Triazole-resistant A. fumigatus isolates were subjected to a mixed-format real time polymerase chain reaction (RT-PCR) assay (AsperGenius®) to detect common cyp51A alterations.

Results: We identified 167 clinical A. fumigatus isolates from 135 patients. Resistance to at least one azole antifungal drug was confirmed in 22/167 (13.2%) of isolates from 18/135 (13.3%) patients, including 12/74 (16.2%) patients with cystic fibrosis (CF). The highest detection rate of azole-resistant A. fumigatus was among the 11- to 20-y age group. All triazole-resistant isolates (n = 22) were resistant to itraconazole, 18 showed cross-resistance to posaconazole and 10 displayed reduced susceptibility to voriconazole. No pan-azole-resistant A. fumigatus was identified. TR34/L98H was identified in 6/22 (27.3%) of azole-resistant isolates and detectable in 5/12 (42%) patients with CF.

Conclusions: In our specialist cardiothoracic centre, the prevalence of triazole-resistant A. fumigatus is alarmingly high (13.2%). The majority of azole-resistant isolates were from patients with CF. We found a higher prevalence of the environmentally driven mutation TR34/L98H in our A. fumigatus isolates than in published UK data from other specialist respiratory centres, which may reflect differing patient populations managed at these institutions.

Keywords: Aspergillus fumigatus; antifungal drugs; azole resistance; cyp51A.

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Antifungal Agents / pharmacology*
  • Aspergillosis / epidemiology
  • Aspergillosis / microbiology*
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / enzymology
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / isolation & purification
  • Child
  • Cystic Fibrosis / complications
  • Cytochrome P-450 Enzyme System / genetics
  • Drug Resistance, Fungal*
  • Female
  • Fungal Proteins / genetics
  • Hospitals
  • Humans
  • London
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Polymorphism, Genetic
  • Prevalence
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Triazoles / pharmacology*
  • Young Adult

Substances

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