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

Resendiz-Sharpe, A.; Mercier, T.; Lestrade, P.P.A.; Beek, M.T. van der; Borne, P.A. von dem; Cornelissen, J.J.; ... ; Dutch-Belgian Mycosis Study Grp (2019)

Article / Letter to editor

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.

• All authors: Resendiz-Sharpe, A.; Mercier, T.; Lestrade, P.P.A.; Beek, M.T. van der; Borne, P.A. von dem; Cornelissen, J.J.; Kort, E. de; Rijnders, B.J.A.; Schauwvlieghe, A.F.A.D.; Verweij, P.E.; Maertens, J.; Lagrou, K.; Dutch-Belgian Mycosis Study Grp
• Date: 2019-09-01
• Journal: Journal of Antimicrobial Chemotherapy
• Volume: 74
• Issue: 9
• Pages: 2759 - 2766
• DOI: doi:10.1093/jac/dkz258