PCR-based detection of Aspergillus fumigatus and absence of azole resistance due to TR34 /L98H in a french multicenter cohort of 137 patients with fungal rhinosinusitis

Abstract

Fungal rhinosinusitis (FRS) has a worldwide distribution, comprises distinct clinical entities but is mostly due to Aspergillus among which Aspergillus fumigatus plays a major role in European countries. Although, there is accumulating evidence for the emergence of environmentally acquired-azole resistance in A. fumigatus (such as TR₃₄ /L98H) in various clinical settings, there is few data for patients with FRS. In this study, we aimed to investigate the prevalence of A. fumigatus azole resistance due to TR₃₄ /L98H in a multicentre cohort of patients with FRS. One hundred and thirty-seven patients with FRS admitted between 2002 and 2016 at four French medical centres were retrospectively enrolled. Clinical and mycological findings were collected. Aspergillus fumigatus and the TR₃₄ /L98H alteration conferring azole resistance were investigated directly from clinical samples using the commercial CE-IVD marked MycoGENIE^® A. fumigatus real-time PCR assay. Fungal ball was the more frequent clinical form (n = 118). Despite the presence of fungal hyphae at direct microscopic examination, mycological cultures remained negative for 83 out of the 137 patients (60.6%). The PCR assay proved to be useful allowing the identification of A. fumigatus and etiological diagnosis in 106 patients (77.4%) compared with 44 patients (32.1%) when using culture as the reference method. Importantly, neither TR₃₄ nor L98H alterations were evidenced.

Keywords: Aspergillus fumigatus; PCR-based detection; TR34/L98H; azole resistance; fungal rhinosinusitis.