Molecular Detection of Azole-Resistant Aspergillus fumigatus in Clinical Samples

• Published in: Frontiers in microbiology Vol. 9; p. 515
• Main Authors: Buil, Jochem B, Zoll, Jan, Verweij, Paul E, Melchers, Willem J G
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.03.2018
• Subjects: antifungal; Aspergillus fumigatus; azole; azole resistance; diagnostics; Microbiology; polymerase chain reaction; azole resistance; antifungal; diagnostics; Aspergillus fumigatus; polymerase chain reaction; azole
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2018.00515

diseases are often caused by . Azoles are the mainstay of therapy, but the management of aspergillosis is hampered by the emergence of azole resistance. Rapid detection of azole resistance might benefit treatment outcome by early treatment modifications. However, the yield of fungal culture in invasive aspergillosis is low and susceptibility testing requires several days to be completed. To overcome the low yield of fungal cultures and slow detection of resistance, it is possible to use molecular tools directly on clinical specimens in order to rapidly detect molecular markers of azole resistance. Molecular tools to detect resistant markers in the gene can be expected to be less sensitive compared to molecular tools to detect DNA as the gene is a single copy gene and the target for DNA is often a multi-copy gene. In this mini-review, we summarize the current molecular tools for detection of azole-resistant directly in clinical material. Several in-house PCR assays have been applied directly on clinical material. Furthermore, two assays are commercial available; the AsperGenius and MycoGENIE. The amplification of resistance markers was successful in 70-100% of samples that were positive for DNA in BAL samples using the AsperGenius assay. Despite using several samples per patient, amplification of resistance markers was only successful in 33-57% of patients with DNA in blood. Furthermore, several sequence based methods have been applied with the benefit of the ability to detect other gene alterations.