The Journal of antimicrobial chemotherapy | 2019
Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients.
Abstract
BACKGROUND\nIncreasing 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.\n\n\nOBJECTIVES\nTo 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.\n\n\nMETHODS\nWe 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\u2009weeks.\n\n\nRESULTS\nWe 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\u2009weeks was higher in voriconazole-resistant cases in all patients (42.3% versus 28.2%, P\u205f=\u205f0.20; and 57.7% versus 36.9%, P\u205f=\u205f0.064) and in non-ICU patients (36.4% versus 21.6%, P\u205f=\u205f0.16; and 54.4% versus 30.7%; P\u205f=\u205f0.035), compared with susceptible ones. ICU patient mortality at 6 and 12\u2009weeks was very high regardless of triazole susceptibility (75.0% versus 66.7%, P\u205f=\u205f0.99; and 75.0% versus 73.3%, P\u205f=\u205f0.99).\n\n\nCONCLUSIONS\nA very high prevalence of voriconazole resistance among culture-positive IA haematology patients was observed. The overall mortality at 12\u2009weeks was significantly higher in non-ICU patients with voriconazole-resistant IA compared with voriconazole-susceptible IA.