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

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

doi:10.1128/AAC.00270-17

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

Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00270-17. doi: 10.1128/AAC.00270-17. Print 2017 Aug.

Authors

Affiliations

¹ Institute of Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany susann.roessler@tu-dresden.de Luis.Ostrosky-Zeichner@uth.tmc.edu.
² Institute for Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany.
³ Department of Internal Medicine I, University Hospital Carl Gustav at the Technische Universität Dresden, Dresden, Germany.
⁴ Department of Pathology, University Hospital Carl Gustav at the Technische Universität Dresden, Dresden, Germany.
⁵ Third Department of Internal Medicine, Hematology and Oncology, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany.
⁶ Institute of Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany.
⁷ Laboratory of Mycology Research, Center for Antimicrobial Resistance and Microbial Genomics, McGovern Medical School, Houston, Texas, USA susann.roessler@tu-dresden.de Luis.Ostrosky-Zeichner@uth.tmc.edu.

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.

Keywords: Aspergillus fumigatus; azole resistance; breakthrough aspergillosis; cyp51A mutation; hematopoietic stem cell transplantation; invasive aspergillosis.

Publication types

Case Reports

MeSH terms

Aged
Alleles
Amphotericin B / therapeutic use
Antifungal Agents / therapeutic use*
Aspergillus fumigatus / drug effects*
Aspergillus fumigatus / genetics*
Azoles / therapeutic use*
Caspofungin
Cytochrome P-450 Enzyme System / genetics*
Drug Resistance, Multiple, Fungal / genetics*
Echinocandins / therapeutic use
Fungal Proteins / genetics*
Humans
Invasive Pulmonary Aspergillosis / drug therapy*
Invasive Pulmonary Aspergillosis / microbiology
Leukemia, Myeloid, Acute / microbiology
Lipopeptides / therapeutic use
Male
Microbial Sensitivity Tests
Mutation / genetics
Treatment Outcome
Triazoles / therapeutic use
Voriconazole / therapeutic use

Substances

Antifungal Agents
Azoles
Echinocandins
Fungal Proteins
Lipopeptides
Triazoles
liposomal amphotericin B
posaconazole
Amphotericin B
Cytochrome P-450 Enzyme System
cytochrome P-450 CYP51A, Aspergillus
Caspofungin
Voriconazole