In vitro antifungal susceptibility profile and genotypic characterization of clinical Aspergillus isolates in Eastern China on behalf of Eastern China Invasive Fungi Infection Group

Med Mycol. 2023 Sep 4;61(9):myad082. doi: 10.1093/mmy/myad082.

Abstract

Aspergillus species is a widespread environmental mould that can cause aspergillosis. The purpose of this study was to investigate the antifungal susceptibility profile and genotypic characterization of clinical Aspergillus isolates from different provinces in Eastern China. The data included the antifungal susceptibility distributions with eight common antifungal drugs, cyp51A gene mutations of triazole-resistant Aspergillus fumigatus sensu stricto, and the genotypic relationships among the A. fumigatus sensu stricto isolates based on microsatellite typing. A. fumigatus sensu lato was the most common clinical Aspergillus species (n = 252), followed by A. flavus (n = 169), A. terreus (n = 37), A. niger (n = 29), and A. nidulans (n = 4). The modal minimum effective concentration values of micafungin and anidulafungin were lower than those of caspofungin for all Aspergillus species. The in vitro efficacy of isavuconazole was similar to that of voriconazole against most Aspergillus species. Sequencing revealed cyp51A gene mutations TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A in four triazole-resistant A. fumigatus sensu stricto. Phylogenetic analyses using microsatellite markers of A. fumigatus sensu stricto revealed that 211 unique genotypes clustered into two clades. The data demonstrate the diversity of clinically relevant Aspergillus species in Eastern China. Routine antifungal susceptibility testing should be performed to monitor the antifungal resistance and guide clinical therapy.

Keywords: Aspergillus species; cyp51A gene mutations; Eastern China; antifungal susceptibility profile; microsatellite typing.

Plain language summary

The 6-year multicenter study collected a total of 491 Aspergillus isolates from Eastern China to investigate the in vitro antifungal susceptibility to eight antifungal drugs, the cyp51A gene mutations of triazole-resistant A. fumigatus sensu stricto, and the genetic relatedness through microsatellite typing.

MeSH terms

  • Animals
  • Antifungal Agents* / pharmacology
  • Aspergillus
  • Aspergillus fumigatus
  • Azoles / pharmacology
  • Drug Resistance, Fungal / genetics
  • Fungal Proteins / genetics
  • Genotype
  • Invasive Fungal Infections* / veterinary
  • Microbial Sensitivity Tests / veterinary
  • Phylogeny
  • Triazoles / pharmacology

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Azoles
  • Triazoles