Azole resistance survey on clinical Aspergillus fumigatus isolates in Spain. 2021

Pilar Escribano, and Belén Rodríguez-Sánchez, and Judith Díaz-García, and María Teresa Martín-Gómez, and Elisa Ibáñez-Martínez, and María Rodríguez-Mayo, and Teresa Peláez, and Elia García-Gómez de la Pedrosa, and Rocío Tejero-García, and José María Marimón, and Elena Reigadas, and Antonio Rezusta, and Cristina Labayru-Echeverría, and Ana Pérez-Ayala, and Josefina Ayats, and Fernando Cobo, and Carmen Pazos, and Leyre López-Soria, and Ana Alastruey-Izquierdo, and Patricia Muñoz, and Jesús Guinea, and
Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

OBJECTIVE We aimed to assess the percentage of azole resistance in Aspergillus fumigatus in Spain. METHODS Thirty participating Spanish hospitals stored all morphologically identified A. fumigatus sensu lato clinical isolates-regardless their clinical significance-from 15 February to 14 May 2019. Isolates showing azole resistance according to the EUCAST 9.3.2 methodology were molecularly identified and the cyp51A gene was studied in A. fumigatus sensu stricto isolates. RESULTS Eight hundred and forty-seven isolates from 725 patients were collected in 29 hospitals (A. fumigatus sensu stricto (n = 828) and cryptic species (n = 19)). Isolates were mostly from the lower respiratory tract (94.0%; 797/847). Only cryptic species were amphotericin B resistant. Sixty-three (7.4%) out of the 847 isolates were resistant to ≥1 azole(s). Azole resistance was higher in cryptic species than in A. fumigatus sensu stricto (95%, 18/19 vs. 5.5%, 45/828); isavuconazole was associated to the lowest number of non-wild type isolates. The dominant mechanism of resistance was the presence of TR34-L98H substitutions (n = 24 out of 63). Out of the 725 patients, 48 (6.6%) carried either cryptic species (n = 14) or A. fumigatus sensu stricto (n = 34; 4.7%) resistant isolates. Aspergillus fumigatus sensu stricto harbouring either the TR34-L98H (n = 19) or TR46/Y121F/T289A (n = 1) mutations were detected in patients in hospitals located at 7/24 studied cities. CONCLUSIONS Of the patients, 6.6% carry azole-resistant A. fumigatus sensu lato isolates in Spain. TR34-L98H is the dominant cyp51A gene substitutions, although its presence is not widespread.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D005656 Fungal Proteins Proteins found in any species of fungus. Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D001228 Aspergillosis Infections with fungi of the genus ASPERGILLUS. Aspergillus Infection,Aspergilloses,Aspergillus Infections,Infection, Aspergillus,Infections, Aspergillus
D001232 Aspergillus fumigatus A species of imperfect fungi from which the antibiotic fumigatin is obtained. Its spores may cause respiratory infection in birds and mammals. Aspergillus fumigates,Neosartorya fumigata,Sartorya fumigata
D001393 Azoles Five membered rings containing a NITROGEN atom. Azole
D013030 Spain Country located between France on the northeast and Portugal on the west and bordered by the Atlantic Ocean and the Mediterranean Sea. The capital is Madrid. Balearic Islands,Canary Islands
D025141 Drug Resistance, Fungal The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation. Antibiotic Resistance, Fungal,Antifungal Drug Resistance,Resistance, Antifungal Drug

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