Aspergillus fumigatus clinical isolates carrying CYP51A TR34/L98H/S297T/F495I mutation detected after 4 years retrospective azole resistance screening test in Brazil.


Pontes L, Beraquet CAG, Arai T, Pigolli GL, Lyra L, Watanabe A, Moretti ML, Schreiber AZ
Antimicrob Agents Chemother. 2019 Dec 23. pii: AAC.02059-19.


Azole antifungals 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 years retrospective azole antifungal resistance screening revealed the two azole-resistant A. fumigatus clinical isolates carrying CYP51A TR34/L98H/S297T/F495I mutation resistance mechanism obtained from two unrelated patients. Broth microdilution antifungal susceptibility showed high MICs for Itraconazole, Posaconazole, and Miconazole. STR typing analysis presented high similarity between these two isolates and clinical isolates with the same mutation reported from the Netherlands, Denmark, China, and Taiwan environmental isolates. Our findings might indicate that active searching for resistant A. fumigatus is necessary. It also represents a concern, considering that our Hospital provides tertiary care assistance to immunocompromised patients, that may be exposed to environmental resistant isolates; 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 patient's own organism. We do not know the potential of this azole-resistant A. fumigatus to spread throughout our country. In this scenario, the impact on the epidemiology and use of antifungal drugs will significantly alter patient care such as in other parts of the world. In summary, this finding is an important contribution to alert hospital microbiology routine laboratories to perform azole resistance surveillance and antifungal susceptibility tests of A. fumigatus causing infection or colonization in high-risk patients for systemic aspergillosis.