Gradient diffusion strips for detecting azole resistance in Aspergillus fumigatus sensu lato. Issue 3 (2nd November 2022)

• Record Type: Journal Article
• Authors: Serrano‐Lobo, Julia; Gómez, Ana; Reigadas, Elena; Muñoz, Patricia; Escribano, Pilar; Guinea, Jesús
• Other Names: Sánchez‐Yebra Waldo investigator.; Lozano Inmaculada investigator.; Marfil Eduardo investigator.; de la Muñoz‐Rosa Montserrat investigator.; Tejero‐García Rocío investigator.; Cobo Fernando investigator.; Castro Carmen investigator.; López Concepción investigator.; Rezusta Antonio investigator.; Peláez Teresa investigator.; Lozano‐Serra Julia investigator.; Jiménez Rosa investigator.; Labayru‐Echeverría Cristina investigator.; Losa‐Pérez Cristina investigator.; Megías‐Lobón Gregoria investigator.; Lorenzo Belén investigator.; Sánchez‐Reus Ferrán investigator.; Ayats Josefina investigator.; Martín Maria Teresa investigator.; Vidal Inmaculada investigator.; Sánchez‐Hellín Victoria investigator.; Ibáñez Elisa investigator.; Valentín Amparo investigator.; Pemán Javier investigator.; Fajardo Miguel investigator.; Pazos Carmen investigator.; Rodríguez‐Mayo María investigator.; Pérez‐Ayala Ana investigator.; Gómez‐García de la Pedrosa Elia investigator.; Guinea Jesus investigator.; Escribano Pilar investigator.; Serrano Julia investigator.; Reigadas Elena investigator.; Rodríguez Belén investigator.; Zvezdanova Estreya investigator.; Díaz‐García Judith investigator.; Núñez Ana investigator.; Machado Marina investigator.; Muñoz Patricia investigator.; Sánchez‐Romero Isabel investigator.; García‐Rodríguez Julio investigator.; del Pozo José Luis investigator.; Rubio‐Vallejo Manuel investigator.; Ruiz de Alegría‐Puig Carlos investigator.; López‐Soria Leyre investigator.; Marimón José María investigator.; Fernández‐Torres Marina investigator.; Hernáez‐Crespo Silvia investigator.;
• Is Part Of: Mycoses. Volume 66:Issue 3(2023)
• Page Start: 196
• Page End: 201
• Publication Date: 2022-11-02
• Subjects: Aspergillus fumigatus -- azole resistance -- EUCAST -- gradient diffusion strips; Pathogenic fungi -- Periodicals; Medical mycology -- Periodicals; 616.969
• DOI: 10.1111/myc.13541
• Languages: English
• ISSNs: 0933-7407

Abstract

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.