Format

Send to

Choose Destination
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

1
Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
2
Department of Haematology, University Hospitals Leuven, Leuven, Belgium.
3
Department of Medical Microbiology, Viecuri Medical Centre, Venlo, The Netherlands.
4
Department of Medical Microbiology, Leiden University Medical Centre, Leiden, The Netherlands.
5
Department of Haematology, Leiden University Medical Centre, Leiden, The Netherlands.
6
Department of Haematology, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands.
7
Department of Haematology, Radboud University Medical Centre, Nijmegen, The Netherlands.
8
Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands.
9
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Centre of Expertise in Mycology, Radboud UMC/CWZ, Nijmegen, The Netherlands.
10
Department of Laboratory Medicine and National Reference Center for Mycosis, Excellence Centre for Medical Mycology (ECMM), University Hospitals Leuven, Leuven, Belgium.

Abstract

BACKGROUND:

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.

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

PMID:
31236587
DOI:
10.1093/jac/dkz258

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center