Aspergillus and azole resistance in cystic fibrosis

Ref ID: 19453

Author:

J. F. Meis,1 J. B. Yntema,2 P. Merkus2 and Dutch Cystic Fybrosis
Fungal Study Group2

Author address:

1CWZ, Nijmegen, the Netherlands and 2Canisius Wilhelmina
Hospital and Radboud University Nijmegen Medical Centre,
Nijmegen, the Netherlands

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Introduction Cystic fibrosis (CF) is a common genetic disorder in
Caucasians with a carrier frequency of 1:20-1:32. The hallmark of
classic CF are chronic infections of the airways due to sticky vis-
cous mucous causing bronchial obstruction resulting in infection,
inflammation and bronchiectasis. Most infectious agents are bacte-
ria but fungi are increasingly recovered when patients become
older. The most isolated filamentous fungus from CF sputum is
Aspergillus. We performed a 3-year prospective multicentre study to
collect filamentous fungi recovered from patients with CF in the
Netherlands.
Methods Standardized routine sputum samples were collected in
four large and three smaller CF Centres in the Netherlands. All sam-
ples were also cultured on mould- selective plates and incubated at
two temperatures. All filamentous fungi were stored and identified
centrally. After initial morphologic identification, molecular confirma-
tion using AFLP and ITS + D1/D2 sequencing was performed. All
Aspergillus fumigatus isolates were additionally screened for presence
of the most common mutations in the CYP51 gene conferring azole
resistance. Results In the period May 2010-May 2013, 4700 respiratory sam-
ples from 715 CF patients had 131 different species of filamentous
fungi cultured. The main species found was A. fumigatus (n = 2383),
which was confirmed by molecular identification. In addition, other
potentially pathogenic fungi were isolated, among others Pseudalle-
scheria/ Scedosporium complex, A. terreus. A. flavus, A. tubingensus, A.
sydowii, Exophiala dermatitidis and many different Penicillium species.
Azole resistance of A. fumigatus isolates was caused by the TR34/
L98H mutation, followed by TR46/ Y121F/ T289A. Only few azole
resistant isolates with single mutations at positions G54W (n = 7),
M220I (n = 3), M220K (n =1) and M220N (n = 1) were found.
Resistance rates in the years 2010 (TR34:3.7%, TR46:1%), 2011
(TR34:4.5%, TR46:2.6%), 2012 (TR34:4.3%, TR46:1%) and 2013
(TR34 3.4%, TR46:1.6%) did not show variation.
Conclusion About 50% of filamentous fungi recovered from respira-
tory samples of CF patients is A. fumigatus. Among these a sizable
number has mutations conferring azole resistance. The large majority
of resistant isolates harbour the environmental mutations TR34 and
the recently described TR46. Azole treatment for Aspergillus of CF
patients should take into account the potential presence of azole
resistance.
This work was supported by the Dutch Cystic Fibrosis Foundation.

Abstract Number: w09-1

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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