Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study

Pieter P. Lestrade*, Robert G. Bentvelsen, Alexander F.A.D. Schauwvlieghe, Steven Schalekamp, Walter J.F.M. van der Velden, Ed J. Kuiper, Judith van Paassen, Ben van der Hoven, Henrich A. van der Lee, Willem J.G. Melchers, Anton F. de Haan, Hans L. van der Hoeven, Bart J.A. Rijnders, Martha T. van der Beek, Paul E. Verweij

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

210 Citations (Scopus)

Abstract

Background
Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%–100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking.
Methods
A 5-year retrospective cohort study (2011–2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated.
Results
Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 and 25% on day 90. In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42. The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy, despite switching to appropriate antifungal therapy after a median of 10 days.
Conclusions
Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality.
Original languageEnglish
Pages (from-to)1463-1471
Number of pages9
JournalClinical Infectious Diseases
Volume68
Issue number9
Early online date11 Oct 2018
DOIs
Publication statusPublished - 1 May 2019

Research programs

  • EMC COEUR-09
  • EMC MM-04-28-01

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