Comparison of the MICs Obtained by Gradient Concentration Strip and EUCAST Methods for Four Azole Drugs and Amphotericin B against Azole-Susceptible and -Resistant Aspergillus Section Fumigati Clinical Isolates

Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01597-19. doi: 10.1128/AAC.01597-19. Print 2020 Feb 21.

Abstract

Reference methods used to assess the drug susceptibilities of Aspergillus fumigatus isolates consisted of EUCAST and CLSI standardized broth microdilution techniques. Considering the increasing rate and the potential impact on the clinical outcome of azole resistance in A. fumigatus, more suitable techniques for routine testing are needed. The gradient concentration strip (GCS) method has been favorably evaluated for yeast testing. The aim of this study was to compare the CGS test with EUCAST broth microdilution for amphotericin B (AMB), posaconazole (PCZ), itraconazole (ITZ), voriconazole (VRZ), and isavuconazole (ISA). A total of 121 Aspergillus section Fumigati strains were collected, including 24 A. fumigatus sensu stricto strains that were resistant to at least one azole drug. MICs were determined using GCS and EUCAST methods. Essential agreement between the 2 methods was considered when MICs fell within ±1 dilution or ±2 dilutions of the 2-fold dilution scale. Categorical agreement was defined as the percentage of strains classified in the same category (susceptible, intermediate, or resistant) with both methods. Essential agreements with ±1 dilution and ±2 dilutions were 96.7, 93.4, 90.0, 89.3, and 95% and 100, 99.2, 100, 97.5, and 100% for AMB, PCZ, ITZ, VRZ, and ISA, respectively. Categorical agreements were 94.3, 86.1, 89.3, and 88.5% for AMB, PCZ, ITZ, and VRZ, respectively. Detection of resistance was missed with the GCS for one strain (4.1%) for PCZ and for 2 strains (8.3%) for ISA. Determination of ITZ MICs using the GCS allowed the detection of 91.7% of azole-resistant strains. The GCS test appears to be a valuable method for screening azole-resistant A. fumigatus clinical isolates.

Keywords: Aspergillus fumigatus; CYP51A; EUCAST; antifungal susceptibility testing; azole resistance; gradient concentration strip.

MeSH terms

  • Amphotericin B / pharmacology*
  • Antifungal Agents / pharmacology*
  • Aspergillus / drug effects
  • Aspergillus / genetics
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / genetics
  • Azoles / pharmacology*
  • Drug Resistance, Fungal / genetics
  • Fungal Proteins / genetics
  • Itraconazole / pharmacology
  • Microbial Sensitivity Tests
  • Nitriles / pharmacology
  • Pyridines / pharmacology
  • Triazoles / pharmacology
  • Voriconazole / pharmacology

Substances

  • Antifungal Agents
  • Azoles
  • Fungal Proteins
  • Nitriles
  • Pyridines
  • Triazoles
  • Itraconazole
  • isavuconazole
  • Amphotericin B
  • Voriconazole