Prospective surveillance of azole resistance in Aspergillus fumigatus isolated from patients with cystic fibrosis at Nantes University Hospital, France

Ref ID: 19380

Author:

F. Morio,1 E. Llasera,1 C. Dumortier,1 E. Sacchetto,1 M. Sakka,1
I. Danner-Boucher,2 A. Haloun2 and P.Le Pape1

Author address:

1CHU de Nantes, France and 2Centre de Reference Maladies
Rares pour la Mucoviscidose (CRCM), CHU de Nantes, France

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Azole resistance in Aspergillus fumigatus is increasingly
reported in several European countries. One mechanism, relying on
the TR34/L98H mutation has probably emerged as a consequence of
the widespread use of triazole fungicides in our environment.
Recently, we reported an 8% prevalence of azole resistance in A. fumigatus
during a retrospective study in patients with cystic fibrosis
(CF)1. We found four patients with A. fumigatus azole-resistant iso-
lates and demonstrated that resistance was mainly driven by TR34/
L98H. Since January 2012, we conducted a prospective survey of
azole resistance in CF patients followed up at our center. Here are
presented the preliminary results.
Methods All respiratory samples from CF patients received at our
laboratory since January 2012 were included prospectively. Routine
mycological identification of the mould isolates was based on macro-
scopic and microscopic morphological characteristics. Aspergillus sec-
tion Fumigati isolates were screened for azole resistance by
subculture on agar plates containing 4 mg/L itraconazole (ITZ). Each
isolate that grew on ITZ-containing agar plates was identified at the
species level by b-tubulin gene sequencing and analysis of the full
coding region of the AfCYP51A gene and its promoter were per-
formed. Minimal inhibitory concentrations of ITZ were determined
according to the EUCAST standardized methodology. Data regarding
azole exposure were collected.
Results Preliminary analysis allowed us to identify 5 A. fumigatus
ITZ-resistant isolates (5 patients, table below). All these patients have
been previously exposed to azole antifungals. Various alterations in
the AfCYP51A gene were evidenced. TR34/L98H isolates were found
in two patients. Mutations G54E and F219I, both previously linked
to azole resistance, were found in two patients (1 and 3). Interest-
ingly, one ITZ-resistant isolate only harbored AfCYP51A mutations
that have been reported in susceptible isolates suggesting non-
Cyp51A-mediated azole resistance.
Conclusions This prospective study of azole resistance in CF patients
allowed us to identify 5 additional patients displaying A. fumigatus
azole-resistant isolates. Azole resistance in CF patients relies on both,
de novo acquisition of resistant isolates from the environment as a
consequence of triazole fungicides use and in vivo selection through
long-term azole therapy. Finally, these preliminary findings confirm
the relatively high prevalence of azole resistance in CF patients at
our center and reinforce the need for regular susceptibility testing in
this patient population.
1Morio F, Aubin GG, Danner-Boucher I, Haloun A, Sacchetto E,
Garcia-Hermoso D, Bretagne S, Miegeville M, Le Pape P. High preva-
lence of triazole resistance in Aspergillus fumigatus, especially medi-
ated by TR/L98H, in a French cohort of patients with cystic fibrosis.
J Antimicrob Chemother. 2012 Aug;67(8):1870-3.

Abstract Number: p024

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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