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    Serrano‐Lobo, Julia; Gómez, Ana; Reigadas, Elena; Muñoz, Patricia; Escribano, Pilar; Guinea, Jesús; Sánchez‐Yebra, Waldo; Lozano, Inmaculada; Marfil, Eduardo; 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; Megías‐Lobón, Gregoria; Lorenzo, Belén; Sánchez‐Reus, Ferrán; Ayats, Josefina; Martín, Maria Teresa; Vidal, Inmaculada; Sánchez‐Hellín, Victoria; Ibáñez, Elisa; Valentín, Amparo; Pemán, Javier; Fajardo, Miguel; Pazos, Carmen; Rodríguez‐Mayo, María; Pérez‐Ayala, Ana; Gómez‐García de la Pedrosa, Elia; Guinea, Jesus; Escribano, Pilar; Serrano, Julia; Reigadas, Elena; Rodríguez, Belén; Zvezdanova, Estreya; Díaz‐García, Judith; Núñez, Ana; Machado, Marina; Muñoz, Patricia; Sánchez‐Romero, Isabel; García‐Rodríguez, Julio; del Pozo, José Luis; Rubio‐Vallejo, Manuel; Ruiz de Alegría‐Puig, Carlos; López‐Soria, Leyre; Marimón, José María; Fernández‐Torres, Marina; Hernáez‐Crespo, Silvia

    Mycoses, March 2023, 2023-Mar, 2023-03-00, 20230301, Volume: 66, Issue: 3
    Journal Article

    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.