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. 2023 Mar;66(3):196-201.
doi: 10.1111/myc.13541. Epub 2022 Nov 2.

Gradient diffusion strips for detecting azole resistance in Aspergillus fumigatus sensu lato

Julia Serrano-Lobo  1   2 , Ana Gómez  1   2 , Elena Reigadas  1   2   3 , Patricia Muñoz  1   2   3   4 , Pilar Escribano  1   2 , Jesús Guinea  1   2   3 ; ASPEIN Study Group
Collaborators, Affiliations

Gradient diffusion strips for detecting azole resistance in Aspergillus fumigatus sensu lato

Julia Serrano-Lobo et al. Mycoses. 2023 Mar.

Abstract

Background: Studies comparing gradient diffusion strips (GDSs) and the EUCAST E.Def 9.4 microdilution method are scarce, thwarted by a low number of isolates, and restricted to selected antifungal agents.

Objectives: We evaluated the performance of GDSs to detect azole resistance in A. fumigatus, including cryptic species.

Patients/methods: A. fumigatus sensu stricto (n = 89) and cryptic species (n = 52) were classified as susceptible or resistant to itraconazole, voriconazole, posaconazole and isavuconazole (EUCAST E.Def 9.4; clinical breakpoints v10). A. fumigatus sensu stricto azole-resistant isolates had the following cyp51A gene mutations: TR34 -L98H (n = 24), G54R (n = 5), TR46 -Y121F-T289A (n = 1), F46Y-M172V-N248T-D255E-E427K (n = 1), F165L (n = 1) and cyp51A gene wild type (n = 3). GDSs (ETEST®, bioMèrieux, Marcy-l'Etoile, France and Liofilchem®, Roseto degli Abruzzi, Italy) MICs were obtained by following the manufacturer's guidelines.

Results: For A. fumigatus sensu stricto, itraconazole MICs >1.5 mg/L, voriconazole >0.38 mg/L, posaconazole >0.75 mg/L, and isavuconazole >0.5 mg/L correctly separated resistant from susceptible isolates with two exceptions. Considering the aforementioned cut-off MICs, sensitivity/specificity values of GDSs to detect azole resistance were: itraconazole (97%/100%), voriconazole (97%/100%), posaconazole (97%/100%) and isavuconazole (93.3%/100%). For cryptic species isolates, voriconazole MICs >1 mg/L and isavuconazole >0.75 mg/L separated resistant isolates from susceptible isolates with 15 and 27 exceptions, respectively. Considering the aforementioned cut-off MICs, sensitivity/specificity values were as follows: voriconazole (68.1%/100%) and isavuconazole (25%/100%). For itraconazole and posaconazole, it was not possible to establish cut-off values.

Conclusions: We set tentative cut-off MIC values to correctly spot resistant Aspergillus fumigatus sensu stricto isolates using GDSs. The performance against cryptic species was poor.

Keywords: Aspergillus fumigatus; EUCAST; azole resistance; gradient diffusion strips.

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References

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