Invasive aspergillosis due to a resistant strain of Aspergillus fumigatus with TR4/L98H mutation in an haematology patient in France

Ref ID: 19415

Author:

L. Millon,1 S. Rocchi,2 E. Daguindau,1 G. Reboux,1 D. Garcia-
Hermoso,3 F. Grenouillet,1 S. Bretagne3 and E. Deconink1

Author address:

1Universit Hopsital, Besancon, France; 2UMR CNRS
ChronoEnvironnement, University of Franche Comte, Besancon,
France and 3Centre National de R!ef!erence Mycologie et
Antifongiques, Institut Pasteur, Paris, France

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objective Azole resistance in Aspergillus fumigatus has been increas-
ingly reported in recent years. The primary acquisition of environ-
mental-resistant isolates is characterized by the dominance of a
single resistance mechanism (TR34/L98H mutation). Only a few
cases of invasive aspergillosis due to resistant strains with the TR34/
L98H mutation have been described thus far (8 cases in the Nether-
lands, one case in Germany, one case in Spain). We describe the first
case of invasive aspergillosis in France due to a multi-azole resistant
strain of Aspergillus fumigatus, with mutation TR32/L98H.
Patient-Methods Mr X, a 63-year-old farmer in Jura, France, was
diagnosed with severe aplastic anemia in 1997. An allogenic hemato-
poietic stem cell transplant was done in January 2011. The patient
presented reactivation of Graft versus Host disease at D130 and D
180, which required increasing the dose of corticoid therapy and cy-
closporin, then tacrolimus, then rituximab in October 2011. Antifun-
gal prophylaxy were given during the entire post graft period, with
voriconazole (Jan-April 2011) then posaconazole (200 mg 3x/day)
(from May 2011). On April 26, 2012, the patient was diagnosed with
probable invasive aspergillosis. Mycological examination showed posi-
tive Aspergillus antigen in serum and positive culture of Aspergillusfumigatus from sputum. As the patient had received azole antifungal
prophylaxy for 16 months, the antifungal therapy was started with a
combination of liposomal amphotericin B and caspofungin. Though a
second Aspergillus fumigatus isolate was obtained from a sputum sam-
ple 15 days later, clinical improvement was obtained. An environ-
mental survey was conducted at the patient’s home (14 air samples).
We also collected samples from the outdoor environment around his
home (27 samples from soil, cereal fields, hay), as he reported the use
of fungicides (prothioconazole- epoxiconazole) in his work
Results The two clinical isolates showed the same resistant pattern
(EUCAST method: resistance to itraconazole (Minimal Inhibition Con-
centration (MIC) >8 lg/mL) and to voriconazole (= 4 lg/mL)).
Sequencing the complete CYP51A gene revealed the presence of the
34 bp tandem repeat and the L98H mutation in both isolates. All
environmental samples were seeded on DG18 medium and on malt
agar supplemented with 4 mg/L of itraconazole. From the 41 envi-
ronmental samples, 145 isolates of Aspergillus fumigatus grew on DG
18 media, and one isolate grew on itraconazole-containing malt
agar. MIC determination and gene sequencing of environmental iso-
lates are ongoing.
Conclusion Our observation provides additional arguments in favor
of recommending active sampling (sputum, bronchoalveolar lavage) to
isolate the Aspergillus strains and perform susceptibility testing in
patients with suspected invasive aspergillosis. It also raises the ques-
tion of reconsidering voriconazole as first-line therapy in patients with
invasive aspergillosis in specific situations (rural, farmer, “¦) where
contact with strains from fields treated with fungicides is likely.

Abstract Number: p175

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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