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J Antimicrob Chemother. 2019 Sep 1;74(9):2759-2766. doi: 10.1093/jac/dkz258.

Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients.

Author information

Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Department of Haematology, University Hospitals Leuven, Leuven, Belgium.
Department of Medical Microbiology, Viecuri Medical Centre, Venlo, The Netherlands.
Department of Medical Microbiology, Leiden University Medical Centre, Leiden, The Netherlands.
Department of Haematology, Leiden University Medical Centre, Leiden, The Netherlands.
Department of Haematology, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands.
Department of Haematology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Centre of Expertise in Mycology, Radboud UMC/CWZ, Nijmegen, The Netherlands.
Department of Laboratory Medicine and National Reference Center for Mycosis, Excellence Centre for Medical Mycology (ECMM), University Hospitals Leuven, Leuven, Belgium.



Increasing resistance of Aspergillus fumigatus to triazoles in high-risk populations is a concern. Its impact on mortality is not well understood, but rates from 50% to 100% have been reported.


To determine the prevalence of voriconazole-resistant A. fumigatus invasive aspergillosis (IA) and its associated mortality in a large multicentre cohort of haematology patients with culture-positive IA.


We performed a multicentre retrospective study, in which outcomes of culture-positive haematology patients with proven/probable IA were analysed. Patients were stratified based on the voriconazole susceptibility of their isolates (EUCAST broth microdilution test). Mycological and clinical data were compared, along with survival at 6 and 12 weeks.


We identified 129 A. fumigatus culture-positive proven or probable IA cases; 103 were voriconazole susceptible (79.8%) and 26 were voriconazole resistant (20.2%). All but one resistant case harboured environment-associated resistance mutations in the cyp51A gene: TR34/L98H (13 cases) and TR46/Y121F/T289A (12 cases). Triazole monotherapy was started in 75.0% (97/129) of patients. Mortality at 6 and 12 weeks was higher in voriconazole-resistant cases in all patients (42.3% versus 28.2%, P = 0.20; and 57.7% versus 36.9%, P = 0.064) and in non-ICU patients (36.4% versus 21.6%, P = 0.16; and 54.4% versus 30.7%; P = 0.035), compared with susceptible ones. ICU patient mortality at 6 and 12 weeks was very high regardless of triazole susceptibility (75.0% versus 66.7%, P = 0.99; and 75.0% versus 73.3%, P = 0.99).


A very high prevalence of voriconazole resistance among culture-positive IA haematology patients was observed. The overall mortality at 12 weeks was significantly higher in non-ICU patients with voriconazole-resistant IA compared with voriconazole-susceptible IA.


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