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Azole resistance survey on clinical Aspergillus fumigatus isolates in Spain
Pilar Escribano1, Belén Rodríguez-Sánchez2, Judith Díaz-García1
1Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Objectives:
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.
Discussion:
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.
Insights
In Spain, 6.6% of patients carried azole-resistant Aspergillus fumigatus. The TR34-L98H substitution was the most common resistance mechanism found in Aspergillus fumigatus sensu stricto.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Clinical Microbiology
Background:
- Azole antifungals are crucial for treating invasive fungal infections.
- Emergence of azole resistance in Aspergillus fumigatus poses a significant public health threat.
- Monitoring resistance patterns is essential for effective patient management.
Purpose of the Study:
- To determine the prevalence of azole resistance in Aspergillus fumigatus clinical isolates across Spain.
- To identify the genetic mechanisms underlying azole resistance.
- To assess the proportion of patients infected with azole-resistant strains.
Main Methods:
- Collection of Aspergillus fumigatus sensu lato isolates from 30 Spanish hospitals between February and May 2019.
- Susceptibility testing to azoles using EUCAST methodology.
- Molecular identification of isolates and sequencing of the cyp51A gene in resistant strains.
Main Results:
- Out of 847 isolates, 7.4% exhibited resistance to at least one azole.
- Azole resistance was significantly higher in cryptic species (95%) compared to Aspergillus fumigatus sensu stricto (5.5%).
- The TR34-L98H substitution in the cyp51A gene was the predominant resistance mechanism (24/63 isolates).
Conclusions:
- 6.6% of patients in Spain were found to carry azole-resistant Aspergillus fumigatus sensu lato.
- TR34-L98H represents the primary genetic driver of azole resistance in Aspergillus fumigatus sensu stricto.
- While common, the widespread geographical distribution of this specific resistance mutation requires further investigation.
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