Background: Azole-resistant Aspergillus fumigatus is an emerging worldwide problem with major
clinical implications. A clinical case of A. fumigatus containing the TR46/Y121F/T289A mutation in the
cyp51A gene was detected in 2013 at Hôpital Erasme in Brussels. A laboratory-based surveillance of
unselected A. fumigatus was set up in order to determine the azole-resistance frequency and
Material/methods: From June 2015 to October 2016, 212 A. fumigatus isolated from 109 patients
hospitalized at Hôpital Erasme were screened by VIPcheckTM azole-resistance detection 4 wells-plates
containing voriconazole, itraconazole and posaconazole. All isolates able to grow on any one of the
azole-containing wells were further investigated for their minimal inhibitory concentrations (MICs) by
Sensititre YeastOne, as well as by cyp51A, cyp51B and hapE sequencing. Epidemiological cutoff’s
based on CLSI guidelines were used for interpretation of the MIC values (0.5 μg/mL for posaconazole,
and 1 μg/mL for voriconazole and itraconazole). Demographic and clinical data were collected from
Results: Twenty-two A. fumigatus isolates (10%) from 14 patients (13%) were azole-resistant by
VIPcheckTM. All isolates showed MICs higher than the epidemiological cut-off values for at least one of
the three triazoles tested (Table 1). cyp51A mutations were observed in 20 A. fumigatus isolates from
12 patients (11%). The TR34/L98H was the most prevalent, followed by TR46/Y121F/T289A. The
N248K mutation was observed in one strain. One patient harboured A. fumigatus isolates with two
different mutations: TR34/L98H and G448S. No mutations were observed in two cases. An isolate with
TR34/L98H showed also a deletion in the cyp51B promotor. No isolates showed mutations at hapE.
All patients but one harboring azole-resistant A. fumigatus were colonized: 30% cystic fibrosis patients
and 30% lung transplant patients. One heart transplant patient was diagnosed for invasive
aspergillosis, and treated with voriconazole. Six-weeks after the treatment, Aspergillus with
TR46/Y121F/T289A was detected in this patient. Similarly, four other patients were exposed to azoles
treatment or prophylaxis before resistant strains were detected. These patients carried A. fumigatus
isolates with TR46/Y121F/T289A, TR34/L98H, TR34/L98H and G448S, or N248K mutations.
Conclusions: This laboratory-based surveillance of unselected A. fumigatus showed a high
prevalence (13%) of azole-resistance in A. fumigatus in our hospital in comparison with other studies.
However, only 1 of 109 patients was suffering from azole-resistant invasive aspergillosis.
Full conference title:
- ECCMID 27th (2017)