scholarly journals Azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation emerging in Belgium, July 2012

2012 ◽  
Vol 17 (48) ◽  
Author(s):  
E Vermeulen ◽  
J Maertens ◽  
H Schoemans ◽  
K Lagrou
Keyword(s):  
The Netherlands ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Resistance Mechanism ◽  
Azole Resistance ◽  
Invasive Infection ◽  
Susceptibility Pattern ◽  
Therapy Failure ◽  
First Case ◽  
Phenotypic Susceptibility

A new azole resistance mechanism in Aspergillus fumigatus consisting of a TR46/Y121F/T289A alteration in the cyp51A gene was recently described in the Netherlands. Strains containing these mutations are associated with invasive infection and therapy failure. This communication describes the first case of fatal invasive aspergillosis caused by TR46/Y121F/T289A outside the Netherlands, in the neighboring country of Belgium, suggesting geographical spread. TR46/Y121F/T289A leads to a recognisable phenotypic susceptibility pattern which should trigger cyp51A genotyping to monitor further spread.

scholarly journals Environmental Study of Azole-Resistant Aspergillus fumigatus and Other Aspergilli in Austria, Denmark, and Spain

2010 ◽  
Vol 54 (11) ◽  
pp. 4545-4549 ◽  
Author(s):  
Klaus Leth Mortensen ◽  
Emilia Mellado ◽  
Cornelia Lass-Flörl ◽  
Juan Luis Rodriguez-Tudela ◽  
Helle Krogh Johansen ◽  
...  
Keyword(s):  
The Netherlands ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Resistance Mechanism ◽  
Soil Samples ◽  
Environmental Study ◽  
Azole Resistance ◽  
Environmental Isolates ◽  
Intrinsic Resistance ◽  
Single Mechanism

ABSTRACT A single mechanism of azole resistance was shown to predominate in clinical and environmental Aspergillus fumigatus isolates from the Netherlands, and a link to the use of azoles in the environment was suggested. To explore the prevalence of azole-resistant A. fumigatus and other aspergilli in the environment in other European countries, we collected samples from the surroundings of hospitals in Copenhagen, Innsbruck, and Madrid, flowerbeds in an amusement park in Copenhagen, and compost bags purchased in Austria, Denmark, and Spain and screened for azole resistance using multidish agars with itraconazole, voriconazole, and posaconazole. EUCAST method E.DEF 9.1 was used to confirm azole resistance. The promoter and entire coding sequence of the cyp51A gene were sequenced to identify azole-resistant A. fumigatus isolates. A. fumigatus was recovered in 144 out of 185 samples (77.8%). Four A. fumigatus isolates from four Danish soil samples displayed elevated azole MICs (8%), and all harbored the same TR/L98H mutation of cyp51A. One A. lentulus isolate with voriconazole MIC of 4 mg/liter was detected in Spain. No azole-resistant aspergilli were detected in compost. Finally, A. terreus was present in seven samples from Austria. Multi-azole-resistant A. fumigatus is present in the environment in Denmark. The resistance mechanism is identical to that of environmental isolates in the Netherlands. No link to commercial compost could be detected. In Spain and Austria, only Aspergillus species with intrinsic resistance to either azoles or amphotericin B were found.

scholarly journals Azole-resistant invasive aspergillosis in a patient with acute myeloid leukaemia in Germany

2012 ◽  
Vol 17 (36) ◽  
Author(s):  
A Hamprecht ◽  
D Buchheidt ◽  
J J Vehreschild ◽  
O A Cornely ◽  
B Spiess ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Myeloid Leukaemia ◽  
Susceptibility Testing ◽  
Resistance Mechanism ◽  
Azole Resistance ◽  
Breakthrough Infection ◽  
Proven Case ◽  
Acute Myeloid

We report the first culture-proven case of invasive aspergillosis (IA) caused by azole-resistant Aspergillus fumigatus in a patient with acute myeloid leukaemia in Germany. IA presented as breakthrough infection under posaconazole prophylaxis. Analysis of the resistance mechanism revealed the TR/L98H mutation in the cyp51A gene, which indicates an environmental origin of the strain. This case underscores the need for monitoring azole resistance in Aspergillus spp. and for routine susceptibility testing of moulds.

scholarly journals Molecular Epidemiology of Aspergillus fumigatus Isolates Harboring the TR34/L98H Azole Resistance Mechanism

2012 ◽  
Vol 50 (8) ◽  
pp. 2674-2680 ◽  
Author(s):  
S. M. T. Camps ◽  
A. J. M. M. Rijs ◽  
C. H. W. Klaassen ◽  
J. F. Meis ◽  
C. M. O'Gorman ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Molecular Epidemiology ◽  
Resistance Mechanism ◽  
Azole Resistance

scholarly journals A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions

2017 ◽  
Vol 13 (1) ◽  
pp. e1006096 ◽  
Author(s):  
Daisuke Hagiwara ◽  
Daisuke Miura ◽  
Kiminori Shimizu ◽  
Sanjoy Paul ◽  
Ayumi Ohba ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Aspergillus Fumigatus ◽  
Resistance Mechanism ◽  
Azole Resistance

scholarly journals Is Azole Resistance in Aspergillus fumigatus a Problem in Spain?

2013 ◽  
Vol 57 (6) ◽  
pp. 2815-2820 ◽  
Author(s):  
Pilar Escribano ◽  
Teresa Peláez ◽  
Patricia Muñoz ◽  
Emilio Bouza ◽  
Jesús Guinea
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Cryptic Species ◽  
Antifungal Susceptibility ◽  
Single Species ◽  
Azole Resistance ◽  
Tubulin Gene ◽  
Complex Species ◽  
Content Type ◽  
Β Tubulin

ABSTRACTAspergillus fumigatuscomplex comprisesA. fumigatusand other morphologically indistinguishable cryptic species. We retrospectively studied 362A. fumigatuscomplex isolates (353 samples) from 150 patients with proven or probable invasive aspergillosis or aspergilloma (2, 121, and 6 samples, respectively) admitted to the hospital from 1999 to 2011. Isolates were identified using the β-tubulin gene, and only 1 isolate per species found in each sample was selected. Antifungal susceptibility to azoles was determined using the CLSI M38-A2 procedure. Isolates were considered resistant if they showed an MIC above the breakpoints for itraconazole, voriconazole, or posaconazole (>2, >2, or >0.5 μg/ml). Most of the samples yielded only 1 species (A. fumigatus[n= 335],A. novofumigatus[n= 4],A. lentulus[n= 3],A. viridinutans[n= 1], andNeosartorya udagawae[n= 1]). The remaining samples yielded a combination of 2 species. Most of the patients were infected by a single species (A. fumigatus[n= 143] orA. lentulus[n= 2]). The remaining 5 patients were coinfected with multipleA. fumigatuscomplex species, althoughA. fumigatuswas always involved; 4 of the 5 patients were diagnosed in 2009 or later. Cryptic species were less susceptible thanA. fumigatus. The frequency of resistance amongA. fumigatuscomplex andA. fumigatusto itraconazole, voriconazole, and posaconazole was 2.5 and 0.3%, 3.1 and 0.3%, and 4.2 and 1.8%, respectively, in the per-isolate analysis and 1.3 and 0.7%, 2.6 and 0.7%, and 6 and 4% in the per-patient analysis. Only 1 of the 6A. fumigatusisolates in which thecyp51Agene was sequenced had a mutation at position G448. The proportion of patients infected by azole-resistantA. fumigatusisolates was low.

scholarly journals Progressive Dispersion of Azole Resistance in Aspergillus fumigatus: Fatal Invasive Aspergillosis in a Patient with Acute Myeloid Leukemia Infected with an A. fumigatus Strain with a cyp51A TR46 Y121F M172I T289A Allele

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Susann Rößler ◽  
Oliver Bader ◽  
Friedrich Stölzel ◽  
Ulrich Sommer ◽  
Birgit Spiess ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
Azole Resistance ◽  
Hematopoietic Stem ◽  
Content Type ◽  
Acute Myeloid

ABSTRACT Patients with hematologic malignancies as well as allogeneic hematopoietic stem cell transplantation (HSCT) patients are at high risk for invasive aspergillosis. Here, we report a culture- and autopsy-proven fatal invasive aspergillosis in an allogeneic HSTC patient which he developed despite posaconazole prophylaxis. The agent was determined to be an azole-resistant Aspergillus fumigatus strain bearing the cyp51A mutation combination TR46 Y121F M172I T289A. At increasing frequency, the azole resistance of A. fumigatus is being reported globally, limiting treatment options and complicating regimens.

scholarly journals First Clinical Isolation of an Azole-Resistant Aspergillus fumigatus Isolate Harboring a TR46 Y121F T289A Mutation in South America

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Guillermina Isla ◽  
Florencia Leonardelli ◽  
Iris N. Tiraboschi ◽  
Nicolás Refojo ◽  
Alejandra Hevia ◽  
...  
Keyword(s):  
United States ◽  
South America ◽  
Aspergillus Fumigatus ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Azole Resistance ◽  
Content Type

ABSTRACT One of the most recently described Aspergillus fumigatus CYP51A-mediated azole resistance mechanisms is TR46 Y121F T289A. Clinical A. fumigatus strains harboring these substitutions have been reported worldwide, with the exception of South America. We describe the first clinical A. fumigatus strain with this resistance mechanism isolated from an Argentinian patient. The strain was isolated in 2009 (1 year after the first-described mutant in United States), demonstrating that these alleles were scattered worldwide earlier than previously thought.

scholarly journals Environmental Hotspots for Azole Resistance Selection of Aspergillus fumigatus, the Netherlands

2019 ◽  
Vol 25 (7) ◽  
pp. 1347-1353 ◽  
Author(s):  
Sijmen E. Schoustra ◽  
Alfons J.M. Debets ◽  
Antonius J.M.M. Rijs ◽  
Jianhua Zhang ◽  
Eveline Snelders ◽  
...  
Keyword(s):  
The Netherlands ◽  
Aspergillus Fumigatus ◽  
Azole Resistance ◽  
Resistance Selection ◽  
Selection Of

scholarly journals Emerging aspergillosis by azole-resistant Aspergillus fumigatus at an intensive care unit in the Netherlands, 2010 to 2013

2016 ◽  
Vol 21 (30) ◽  
Author(s):  
Judith van Paassen ◽  
Anne Russcher ◽  
Astrid WM in 't Veld - van Wingerden ◽  
Paul E Verweij ◽  
Eduard J Kuijper
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
The Netherlands ◽  
Aspergillus Fumigatus ◽  
Resistance Mechanisms ◽  
Antifungal Treatment ◽  
University Hospital ◽  
Resistant Isolate ◽  
Azole Resistance ◽  
Icu Patients

The prevalence of invasive aspergillosis (IA) at the intensive care unit (ICU) is unknown and difficult to assess since IA also develops in patients lacking specific host factors. In the Netherlands, increasing azole-resistance in Aspergillus fumigatus complicates treatment of patients with IA. The aim of this study was to determine the prevalence of IA by azole-resistant A. fumigatus at the ICU among patients receiving antifungal treatment and to follow their clinical outcome and prognosis. A retrospective cohort study was conducted in a university hospital ICU from January 2010 to December 2013. From all patients who received antifungal treatment for suspected IA, relevant clinical and microbiological data were collected using a standardised questionnaire. Of 9,121 admitted ICU-patients, 136 had received antifungal treatment for suspected IA, of which 38 had a positive A. fumigatus culture. Ten of the 38 patients harboured at least one azole-resistant isolate. Resistance mechanisms consisted of alterations in the cyp51A gene, more specific TR34/L98H and TR46/T289A/Y121F. Microsatellite typing did not show clonal relatedness, though isolates from two patients were genetically related. The overall 90-day mortality of patients with IA by azole-resistant A. fumigatus and patients with suspicion of IA by azole-susceptible isolates in the ICU was 100% (10/10) vs 82% (23/28) respectively. We conclude that the changing pattern of IA in ICU patients requires appropriate criteria for recognition, diagnosis and rapid resistance tests. The increase in azole resistance rates also challenges a reconsideration of empirical antifungal therapy.

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