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.

نویسندگان

  • Susann Rößler
  • Oliver Bader
  • Friedrich Stölzel
  • Ulrich Sommer
  • Birgit Spiess
  • Stephan Geibel
  • Dieter Buchheidt
  • Uwe Groß
  • Gustavo Baretton
  • Enno Jacobs
  • Luis Ostrosky-Zeichner
چکیده

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.

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منابع مشابه

Aspergillus fumigatus harbouring the sole Y121F mutation shows decreased susceptibility to voriconazole but maintained susceptibility to itraconazole and posaconazole.

OBJECTIVES Voriconazole, itraconazole and posaconazole are members of the azole family and widely used for the treatment of aspergillosis. They act by inhibiting the activity of the fungal Cyp51A enzyme. The emergence of environmental azole-resistant Aspergillus fumigatus strains raises major concerns for human health. METHODS Recently, a new cyp51A-mediated resistance mechanism (namely TR46/...

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Aspergillosis due to voriconazole highly resistant Aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles.

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First detection of Aspergillus fumigatus azole-resistant strain due to Cyp51A TR46/Y121F/T289A in an azole-naive patient in Spain

We report the first isolation of a voriconazole-resistant Aspergillus fumigatus strain harbouring the azole resistance mechanism TR46/Y121F/T289A, recovered from an azole-naive patient in Spain with chronic obstructive pulmonary disease. This new finding in Spain suggests the spread of this resistance mechanism and reinforces the need for antifungal susceptibility surveillance.

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First description of azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation in France.

Azole resistance in Aspergillus fumigatus is an emerging public health concern. Recently, a novel fungicide-driven mutation in the cyp51A gene and its promoter, TR46/Y121F/T289A, leading to high-level resistance to voriconazole has been identified in The Netherlands, Belgium, Germany, Denmark, Tanzania, and India in both clinical and environmental samples. Here we report the first description o...

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Azole-resistant Aspergillus fumigatus with the environmental TR46/Y121F/T289A mutation in India.

Sir, Triazole antifungals are the mainstay of therapy for patients with aspergillosis. Notably, the mortality associated with aspergillosis is high and the rate of treatment failure is much higher if patients are infected with multiple-triazole-resistant (MTR) Aspergillus fumigatus. MTR A. fumigatus strains with the mutation TR34/ L98H occur both in azole-treated as well as in azole-naive patie...

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عنوان ژورنال:
  • Antimicrobial agents and chemotherapy

دوره 61 8  شماره 

صفحات  -

تاریخ انتشار 2017