Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study. (11th October 2018)

• Record Type: Journal Article
• Authors: Lestrade, Pieter P; Bentvelsen, Robbert G; Schauwvlieghe, Alexander F A D; Schalekamp, Steven; van der Velden, Walter J F M; Kuiper, Ed J; van Paassen, Judith; van der Hoven, Ben; van der Lee, Henrich A; Melchers, Willem J G; de Haan, Anton F; van der Hoeven, Hans L; Rijnders, Bart J A; van der Beek, Martha T; Verweij, Paul E
• Is Part Of: Clinical infectious diseases. Volume 68:Number 9(2019)
• Page Start: 1463
• Page End: 1471
• Publication Date: 2018-10-11
• Subjects: invasive aspergillosis -- Aspergillus fumigatus -- voriconazole resistance -- mortality; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciy859
• Languages: English
• ISSNs: 1058-4838

Abstract

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 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038). 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. Abstract : A multicenter, retrospective, cohort study showed a 21% higher day 42 mortality in voriconazole-resistant invasive aspergillosis compared with voriconazole-susceptible cases. In resistant cases, switch to appropriate antifungal therapy was associated with increased mortality compared with patients who directly received appropriate antifungal therapy.