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

D. Seidel1 , O.A. Cornely2 , P. Köhler1,3, J. Meis4 , M. Zarrouk3 , J. Salmanton-Garcia3 , D. Arenz5 , O. Blennow6 , D. Buchheidt7 , J.-J. Vehreschild3 , N. Alakel8 , A. Bergeron9 , G. Desoubeaux10, I. FalcesRomero11, N. Klimko12, K. Lagrou13, C. Lass-Flörl14, Y. Le Govic15, J. Maertens16, A. Ostojic17, J. Prattes18 , Z. Racil19, A. Reséndiz Sharpe16, E. Schalk20, M. Stanzani21, J. Steinmann22, W. Melchers23, M.J.G.T. Vehreschild24, P.E. Verweij23

Author address: 

1Department I Of Internal Medicine, Ecmm Excellence Centre Of Medical Mycology, Cologne Excellence Cluster On Cellular Stress Responses In Aging-associated Diseases (cecad), University Hospital Cologne, Cologne, Germany, 2Department I Of Internal Medicine, Ecmm Excellence Centre Of Medical Mycology, Cologne Excellence Cluster On Cellular Stress Responses In Aging-associated Diseases (cecad), German Centre For Infection Research, Partner Site Bonn-cologne, Clinical Trials C, University Hospital Cologne, Cologne, Germany, 3Department I Of Internal Medicine, University Hospital of Cologne, Cologne, Germany, 4Department Of Medical Microbiology And Infectious Diseases, Excellence Center For Medical Mycology (ecmm), Canisius Wilhelmina Hospital, Nijmegen, Netherlands, 5Department I For Internal Medicine, Excellence Center For Medical Mycology (ecmm), University of Cologne, Cologne, Germany, 6Karolinska University Hospital, Stockholm, Sweden, 7Mannheim University Hospital, Heidelberg University,, Mannheim, Germany, 8University Hospital Dresden, Dresden, Germany, 9Université Paris Diderot, APHP Saint-Louis Hospital, Paris, France, 10Cepr Inserm U1100, Université de Tours, Tours, France, 11Hospital Universitario La Paz, Madrid, Spain, 12Department Of Clinical Mycology, Allergology And Immunology, North-Western State Medical University n.a. I.I. Mechnikov, Saint-Petersburg, Russian Federation, 13Clinical Bacteriology And Mycology, Katholieke Universiteit Leuven, Leuven, Belgium, 14Div Hygiene & Med. Microbiology, Med. Univ. Innsbruck, Innsbruck, Austria, 15Groupe d'Etude des Interactions Hôte Pathogène (GEIHP), Université d'Angers, Angers Cedex , France, 16KU Leuven, Leuven, Belgium, 17University Hospital Centre Zagreb, Zagreb, Croatia, 18Section Of Infectious Diseases And Tropical Medicine, Medical University of Graz, Graz, Austria, 19Department Of Internal Medicine - Hematology And Oncology, University Hospital Brno, Brno, Czech Republic, 20Otto-vonGuericke University, Magdeburg, Germany, 21"Lorenzo e Ariosto Seràgnoli" S'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy, 22Institute Of Clinical Hygiene, Medical Microbiology And Clinical Infectiology, Klinikum Nuernberg, Nuremberg, Germany, 23Medical Microbiology, RadboudUMC, Nijmegen, Netherlands, 24Uniklinikum Frankfurt, Med. Klinik II, Infektiologie, Frankfurt, Germany


Objectives: In recent years, survival of patients with invasive aspergillosis (IA) has improved mainly due to availability of extended spectrum triazoles. These advances are jeopardized by the emergence of azole resistance in Aspergillus fumigatus, the most common causative pathogen of IA. Despite several studies suggesting high probability of azole treatment failure in patients with azole-resistant isolates, the clinical implications of azole-resistant IA compared to azole-susceptible IA remain unclear. Thus, we seek to describe the epidemiology and determine the efficacy of antifungal therapy in patients with documented azole-resistant IA compared to azole-sensitive IA in patients with hematological malignancy.

Methods: In patients with hematological malignancies, cases of proven or probable IA (EORTC/MSG 2008) caused by A. fumigatus are registered. Retrospective data are documented, comprising demographics, diagnosis, treatment, response and outcome. Participating sites provided susceptibility results or isolates. Provided isolates were analyzed in a central laboratory.

Results: Since January 2018, 51 sites in 15 countries worldwide enrolled 154 cases diagnosed with IA between 2010 and 2019, of which 23 (14.9%) had azole-resistant IA. Of 44 cases, the respective clinical fungal isolate was analyzed in the central laboratory. A mixed fungal infection was reported for 34 patients (22.1%), 1 (2.9%) in the azole-resistant group; most were related to non-fumigatus Aspergillus species (n = 12, 35.3%) and non-Aspergillus molds (n = 10, 29.4). Most patients were male (n = 98, 63.6%); 19 (82.6%) in the azole-resistant group, 79 (60.3%) in the azole-susceptible group. Age was documented in categories instead of the exact age. Median age group was 50-69 years in both groups (ranging from 7-11 to 70-89 years for azole-resistant cases, 1-12 months to 70-89 years for azolesusceptible cases). Underlying disease and survival are shown in the table. 

Conclusion: A worldwide network of investigators contributes to the CLARITY registry study. Completion of recruitment and subsequent data analysis are planned for 2019. Further sites may be added if azole resistant cases are encountered. 



abstract No: 


Full conference title: 

9th Trends in Medical Mycology Conference 2019
    • TIMM (2019)