Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study.
Clin Infect Dis. 2018 Oct 11;:
Authors: Lestrade PP, Bentvelsen RG, Schauwvlieghe AFAD, Schalekamp S, van der Velden WJFM, Kuiper EJ, van Paassen J, van der Hoven B, van der Lee HA, Melchers WJG, de Haan AF, van der Hoeven HL, Rijnders BJA, van der Beek MT, Verweij PE
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 Aspergillusfumigatus, 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 at 3 university medical centers 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 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038), corresponding with a hazard ratio of 1.4 (day 42 95% confidence interval, 0.8 to 2.5; P = .272). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P = .045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P = .016), 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.
PMID: 30307492 [PubMed - as supplied by publisher]