Aspergillus fumigatus Clinical Isolates Carrying CYP51A with TR34/L98H/S297T/F495I Substitutions Detected after Four-Year Retrospective Azole Resistance Screening in Brazil
| Autor: | Caio Augusto Gualtieri Beraquet, Maria Luiza Moretti, Teppei Arai, Luzia Lyra, Lais Pontes, Angelica Zaninelli Schreiber, Akira Watanabe, Guilherme Leite Pigolli |
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| Rok vydání: | 2019 |
| Předmět: |
Azoles
medicine.medical_specialty Posaconazole Antifungal Agents Itraconazole Mutation Missense Microbial Sensitivity Tests Aspergillosis Aspergillus fumigatus Microbiology Fungal Proteins 03 medical and health sciences Cytochrome P-450 Enzyme System Drug Resistance Fungal Epidemiology medicine Humans Pharmacology (medical) Typing 030304 developmental biology Retrospective Studies Pharmacology 0303 health sciences biology 030306 microbiology business.industry Broth microdilution biology.organism_classification medicine.disease Infectious Diseases Tandem Repeat Sequences Susceptibility Miconazole business Brazil medicine.drug Microsatellite Repeats |
| Zdroj: | Antimicrob Agents Chemother |
| ISSN: | 1098-6596 |
| Popis: | Azole antifungal resistance in Aspergillus fumigatus is a worldwide concern. As in most public hospitals in Brazil, antifungal susceptibility tests are not routinely performed for filamentous fungi at our institution. A 4-year retrospective azole antifungal resistance screening revealed two azole-resistant A. fumigatus clinical isolates carrying the CYP51A TR34 (34-bp tandem repeat)/L98H (change of L to H at position 98)/S297T/F495I resistance mechanism mutations, obtained from two unrelated patients. Broth microdilution antifungal susceptibility testing showed high MICs for itraconazole, posaconazole, and miconazole. Short tandem repeat (STR) typing analysis presented high levels of similarity between these two isolates and clinical isolates with the same mutations reported from the Netherlands, Denmark, and China, as well as environmental isolates from Taiwan. Our findings might indicate that active searching for resistant A. fumigatus is necessary. They also represent a concern considering that our hospital provides tertiary care assistance to immunocompromised patients who may be exposed to resistant environmental isolates. We also serve patients who receive prophylactic antifungal therapy or treatment for invasive fungal infections for years. In these two situations, isolates resistant to the antifungal in use may be selected within the patients themselves. We do not know the potential of this azole-resistant A. fumigatus strain to spread throughout our country. In this scenario, the impact on the epidemiology and use of antifungal drugs will significantly alter patient care, as in other parts of the world. In summary, this finding is an important contribution to alert hospital laboratories conducting routine microbiological testing to perform azole resistance surveillance and antifungal susceptibility tests of A. fumigatus isolates causing infection or colonization in patients at high risk for systemic aspergillosis. |
| Databáze: | OpenAIRE |
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