1598 - Clinical implications of azole-resistant vs. azole-susceptible invasive aspergillosis in hematological malignancy (CLARITY) – a multicenter study

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Presenting Author(s)

Danila Seidel

Scientist
University Hospital of Cologne
Cologne, Nordrhein-Westfalen, Germany
Disclosure: Basilea (Other Financial or Material Support, travel grant)

Co-Author(s)

OC

Oliver A. Cornely

Prof.
University of Cologne, Faculty of Medicine and University Hospital Cologne
Cologne, Nordrhein-Westfalen, Germany
Disclosure: Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees)
MZ

Marouan Zarrouk

Dr
University Hospital of Cologne
Cologne, Nordrhein-Westfalen, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
PK

Philipp Koehler

Medical Doctor
University Hospital Cologne, Cologne, Germany
Cologne, Nordrhein-Westfalen, Germany
Disclosure: Akademie für Infektionsmedizin e.V., (Other Financial or Material Support, Personal fees)Astellas Pharma GmbH (Other Financial or Material Support, Personal fees)Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany (Other Financial or Material Support, Other)Gilead Sciences GmbH (Other Financial or Material Support, Personal fees)GPR Academy Ruesselsheim (Speaker's Bureau)Miltenyi Biotec GmbH (Other Financial or Material Support, Non-financial support)MSD Sharp & Dohme GmbH (Other Financial or Material Support, Personal fees)Noxxon N.V. (Speaker's Bureau)University Hospital, LMU Munich (Other Financial or Material Support, Personal fees)
JM

Jacques F. Meis

Dr.
Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
Nijmegen, Gelderland, Netherlands
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JS

Jon Salmanton-García

University of Cologne, Faculty of Medicine and University Hospital of Cologne
Cologne, NRW
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JV

Jörg Janne Vehreschild

Prof.
University Hospital of Cologne, ECMM Excellence Center, Cologne, Germany
Cologne, Nordrhein-Westfalen, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MC

Martin Christner

Dr.
Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Hamburg, Hamburg, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SG

Stefanie K. Gräfe

Student
University Hospital of Cologne, ECMM Excellence Center, Cologne, Germany, University of Hamburg, Faculty of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Cologne, Nordrhein-Westfalen, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
IF

Iker Falces-Romero

Dr.
Hospital Universitario La Paz
Madrid, Madrid, Spain
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
KL

Katrien Lagrou

Professor
University Hospitals Leuven & KU Leuven
Leuven, Vlaams-Brabant, Belgium
Disclosure: FUJIFILM WAKO (Speaker's Bureau)Gilead (Consultant, Speaker's Bureau)MSD (Consultant, Speaker's Bureau, Other Financial or Material Support, travel grant)Pfizer (Speaker's Bureau, travel grant)SMB Laboratoires Brussels (Consultant)
Johan A. Maertens

Professor
KU Leuven
Leuven, Brussels Hoofdstedelijk Gewest, Belgium
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AR

Agustín Reséndiz- Sharpe

Student
KU Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
ZR

Zdenek Racil

Prof.
Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic
Disclosure: Astellas (Grant/Research Support, Speaker's Bureau, travel grant)
BW

Barbora Weinbergerová

Dr.
Faculty Hospital Brno, Brno, Czech Republic
Brno, Hlavni mesto Praha, Czech Republic
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MV

Maricela Valerio

Physician
Hospital General Universitario Gregorio Marañón. Clinical Microbiology and Infectious Diseases Department. Instituto de Investigación Sanitaria Gregorio Marañón
Madrid, Madrid, Spain
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
PM

Patricia Muñoz

Prof.
Hospital General Universitario Gregorio Marañón. Clinical Microbiology and Infectious Diseases Department, Madrid, Spain
Madrid, Madrid, Spain
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
OB

Ola Blennow

Prof
Karolinska University Hospital
Stockholm, Stockholms Lan, Sweden
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BR

Blandine Rammaert

Dr.
CHU Poitiers, Infectious Disease, Poitiers, France
Poitier, Poitou-Charentes, France
Disclosure: Gilead (Speaker's Bureau, Other Financial or Material Support, travel grant)Merck/MSD (Speaker's Bureau)Pfizer (Other Financial or Material Support, travel grant)
AO

Alen Ostojic

Dr.
University Hospital Centre Zagreb, Zagreb, Croatia
Zagreb, Zagrebacka, Croatia
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
YL

Yohann Le Govic

Dr.
University Hospital Angers, Angers, France
Angers, Nord-Pas-de-Calais, France
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CL

Cornelia Lass-Flörl

Prof
Medical University of Innsbruck
Innsbruck, Tirol, Austria
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SR

Susann Rössler

Dr.
Technische Universität Dresden, Institute of Medical Microbiology and Hygiene, Dresden, Germany
Dresden, Sachsen, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Kv

Karin van Dijk

Dr.
Amsterdam UMC, location VUmc, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Nd

Nick de Jong

Dr.
Amsterdam UMC, location VUmc, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
JS

Jörg Steinmann

Prof
Paracelsus Medical University
Nuremberg, Bayern, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
GD

Guillaume Desoubeaux

Prof
University of Tours
Tours, Pays de la Loire, France
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
NA

Nael Alakel

Dr
Department of Internal Medicine I, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany
Dresden, Sachsen, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
NK

Nikolay Klimko

Dr.
North-Western State Medical University named after I.I. Mechnikov
St. Petersburg, Adygeya, Russia
Disclosure: Astellas (Speaker's Bureau)Gilead (Speaker's Bureau)Merck/MSD (Speaker's Bureau)Pfizer (Speaker's Bureau)
ES

Enrico Schalk

Prof
Otto-von-Guericke University
Magdeburg, Thuringen, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MB

Marie-Pierre Brenier-Pinchart

Dr.
Parasitology-Mycology, Centre hospitalier Grenoble Alpes, France
Grenoble Alpes, Rhone-Alpes, France
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CG

Carolina Garcia-Vidal

Dr.
Hospital Clinic, Department of Hematology, Barcelona, Spain
Barcelona, Catalonia, Spain
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AB

Anne Bergeron

Dr.
Université Paris Diderot, APHP Saint-Louis Hospital, Paris, France
Paris, Ile-de-France, France
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SC

Sung-Yeon Cho

Clinical Assistant Professor
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
Seoul, Seoul-t'ukpyolsi, Republic of Korea
Disclosure: Gilead (Grant/Research Support, Speaker's Bureau)Merck Sharp & Dohme (Grant/Research Support, Speaker's Bureau)Pfizer (Grant/Research Support, Speaker's Bureau)
WM

Willem J.G. Melchers

Dr.
Radboud University Medical Center, Nijmegen, The Netherlands
Nijmegen, Noord-Holland, Netherlands
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MV

Maria J.G.T. Vehreschild

Dr.
University of Cologne, Faculty of Medicine and University Hospital of Cologne
Cologne, Niedersachsen, Germany
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
PV

Paul E. Verweij

Prof.
Radboud University Medical Center, Nijmegen, The Netherlands
Nijmegen, Noord-Brabant, Netherlands
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Background: Advances in the survival of patients with invasive aspergillosis (IA) are jeopardized by the emergence of azole resistance in Aspergillus fumigatus, which has been associated with high probability of azole treatment failure. The clinical implications of azole-resistant IA compared to azole-susceptible IA remain unclear. Thus, we seek to describe the epidemiology and to determine the efficacy of antifungal therapy in patients with documented azole-resistant IA compared to azole-susceptible IA in patients with hematological malignancy.

Methods: For proven and probable IA (EORTC/MSG 2019) caused by A. fumigatus in patients with hematological malignancies retrospective data were documented, comprising demographics, diagnosis, treatment, response, and outcome. Sites provided susceptibility results or respective isolates for analysis in a central laboratory.

Results: Sites in 16 countries worldwide enrolled 187 cases diagnosed with IA between 2010 and 2019; 31 (16.6%) were resistant to at least one of the clinical azoles. Fungal isolates were available from 42 cases. A mixed fungal infection was reported for 32 patients (17.1%), most were related to non‑fumigatus Aspergillus and non‑Aspergillus molds (n=22, 69%). Most patients were male (66.8%) and overall the majority of patients were in the age groups between 50 and 89 years (71%). Amphotericin B was used for treatment in 24 (77%) patients with azole-resistant IA, compared to 76 (49%) in the azole-susceptible group (lipid-based formulation in 98%); only five (16%) patients with azole-resistant IA were treated with an azole alone vs. 57 (36%) of those with azole-susceptible IA. Overall, all-cause mortality rate was higher for patients with azole-resistant compared to azole-susceptible IA (74.2% vs. 53.8%, log rank P=0.004), the 8 patients with an azole-resistant IA treated in the intensive care unit died within 1 month (Figure 1). Details on underlying disease and survival are given in Table 1.Table 1. Underlying hematological malignancy and clinical outcome of patients with azole-resistant and azole-susceptible invasive aspergillosis

Figure 1. Intensive care unit 1-year survival probability for patients with azole-resistant and azole-susceptible invasive aspergillosis

Conclusion: Azole-resistance in IA is associated with worse outcome, especially in critically ill patients. Susceptibility testing should be considered in patients with a suspected azole-resistant IA to support treatment decisions.