Azole resistance in Aspergillus fumigatus isolates from lung transplant recipients with cystic fibrosis: preliminary results

Ref ID: 19378

Author:

F. Choukri,2 F. Morio,3 R. Guillemain,4 V. Boussaud,4 C. Amrein,4
E.M. Billaud,5 P.Le Pape,3 J. Guillot,6 F. Botterel2 and
E. Dannaoui1

Author address:

1Mycology, AP-HP, H^opital Europ!een Georges Pompidou and
UMR BIPAR, Dynamyc, Paris, France; 2Mycology, APHP,
H^opital Henri Mondor, and UMR BIPAR, Dynamyc, Cr!eteil,
France; 3Parasitologie-Mycologie, Institut de Biologie, CHU de
Nantes and EA115

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Azole resistance in Aspergillus fumigatus is an emerging
problem. The mechanism of resistance is mostly related to mutations
in the CYP51A gene encoding 14-alpha-demethylase, the target of
azoles drugs.
Azole resistance can be probably acquired through two distinct
ways that are long term azole treatment or inhalation of de novo
azole resistant isolates from our environment. Importantly, both sce-
nario can be distinguished as their underlying mechanisms differ, the
latter involving not only mutations in the CYP51A gene but also a
tandem repeat in its promoter region.
The aim of the study was to screen for azole resistance a collection
of A. fumigatus isolates recovered from cystic fibrosis lung-transplant
recipients (CF-LTx) over a 12-year period (2001-2012) at a single
center. The molecular mechanisms leading to azole resistance were
also investigated.
Methods The screening was performed by subculturing each isolate
on RPMI agar plates supplemented with itraconazole (4 mg/L) and
voriconazole (1 mg/L). In vitro resistance was confirmed by the EU-
CAST reference method. EUCAST clinical breakpoints were used to
categorize the isolates. For each azole resistant isolate, the whole
CYP51A gene and its promoter were sequenced and compared with
that of a wild type isolate (GenBank acc. number AF338659).
Results We present here preliminary results for three patients
(Table) with A. fumigatus azole resistant isolates.
Most of the isolates displayed azole cross-resistance. TR34/L98H
was the most prevalent mutation being recovered from 5 out of the
8 isolates (in patients 1 and 2). At least for patient 1, our data sup-
port the acquisition of the azole resistant isolate through environ-
mental exposure as this patient had not been given azole therapy
before recovering the first azole-resistant isolate. Other amino acid
substitutions (codons 54 and 216) have been previously reported in
patients receiving long term therapy suggesting that both mutations
are probably the result of selective pressure in the patient itself.
Conclusions This preliminary study confirmed the occurrence of
azole resistance (with distinct molecular mechanisms) in A. fumigatus
isolates recovered from cystic fibrosis lung transplant patients. These findings highlight again the need for systematic antifungal suscepti-
bility testing of Aspergillus spp. recovered in this patient population.

Abstract Number: p018

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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