학술논문
Gradient diffusion strips for detecting azole resistance in Aspergillus fumigatus sensu lato.
Document Type
Article
Author
Serrano‐Lobo, Julia; Gómez, Ana; Reigadas, Elena; Muñoz, Patricia; Escribano, Pilar; Guinea, Jesús; Sánchez‐Yebra, Waldo; Lozano, Inmaculada; Marfil, Eduardo; de la Muñoz‐Rosa, Montserrat; Tejero‐García, Rocío; Cobo, Fernando; Castro, Carmen; López, Concepción; Rezusta, Antonio; Peláez, Teresa; Lozano‐Serra, Julia; Jiménez, Rosa; Labayru‐Echeverría, Cristina; Losa‐Pérez, Cristina
Source
Subject
*DIFFUSION gradients
*ASPERGILLUS fumigatus
*ITRACONAZOLE
*VORICONAZOLE
*ANTIFUNGAL agents
*GENETIC mutation
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Language
ISSN
0933-7407
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. [ABSTRACT FROM AUTHOR]