Surveillance for azoles resistance in Aspergillus spp. highlights a high number of amphotericin B-resistant isolates

Mycoses. 2018 Jun;61(6):360-365. doi: 10.1111/myc.12759. Epub 2018 Mar 23.

Abstract

Aspergillus spp. are the most common invasive mould infection and are responsible for high mortality. Aspergillus fumigatus is currently of interest because resistance to azole antifungals has emerged. The Campinas University Hospital (HC-UNICAMP) receives high-risk patients susceptible to opportunistic infections but there have been no reports of resistant A. fumigatus. This study aimed to assess the susceptibility profile of Aspergillus isolates, specifically looking for azole resistance. ITS and β-tubulin DNA sequencing was performed on 228 sequential clinical isolates. Broth microdilution susceptibility testing was performed for all isolates. A. fumigatus represented 74% of the isolates followed by Aspergillus flavus (12%). Nine A. fumigatus isolates from 9 different patients showed high MIC values to at least 1 azole, but cyp51A polymorphisms were detected in only 6 isolates and none correlated with known resistance mutations. The most troubling observation was that the minimum inhibitory concentration for amphotericin B was elevated (≥2 mg L-1 ) in 87% of patients with A. flavus isolates and 43% with Aspergillus fumigatus isolates. Given that amphotericin B is used to treat azole-resistant infections, these data highlight the need for continuous surveillance in Aspergillus for all antifungal resistance to implement correct treatment strategies for the management of these pathogens.

Keywords: Aspergillosis; Aspergillus spp.; amphotericin B resistance; antifungal susceptibility; azole resistance.

MeSH terms

  • Amphotericin B / pharmacology*
  • Antifungal Agents / pharmacology*
  • Aspergillosis / microbiology
  • Aspergillus / drug effects*
  • Aspergillus / genetics
  • Aspergillus / isolation & purification
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / isolation & purification
  • Azoles / pharmacology*
  • DNA, Ribosomal Spacer / genetics
  • Drug Resistance, Fungal*
  • Genotype
  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • Sequence Analysis, DNA
  • Tubulin / genetics

Substances

  • Antifungal Agents
  • Azoles
  • DNA, Ribosomal Spacer
  • Tubulin
  • Amphotericin B

Associated data

  • GENBANK/AF338659