Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Department of Haematology, University Hospitals Leuven, Leuven, Belgium.
J Antimicrob Chemother. 2019 Sep 1;74(9):2759-2766. doi: 10.1093/jac/dkz258.
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.
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.
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.
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).
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.
烟曲霉对三唑类药物的耐药性在高危人群中不断增加，令人担忧。其对死亡率的影响尚不清楚，但已有 50%至 100%的报告率。
在一项大型血液病患者曲霉菌培养阳性侵袭性曲霉菌病（IA）的多中心队列研究中，确定伏立康唑耐药烟曲霉侵袭性曲霉菌病的流行率及其相关死亡率。
我们进行了一项多中心回顾性研究，分析了培养阳性血液病患者曲霉菌病的结果。根据分离株的伏立康唑药敏性（EUCAST 肉汤微量稀释试验）对患者进行分层。比较了真菌学和临床数据，以及 6 周和 12 周的生存率。
我们共确定了 129 例烟曲霉培养阳性的确诊或疑似 IA 病例；103 例为伏立康唑敏感（79.8%），26 例为伏立康唑耐药（20.2%）。除了一个耐药病例之外，所有耐药病例的 cyp51A 基因中均存在与环境相关的耐药突变：TR34/L98H（13 例）和 TR46/Y121F/T289A（12 例）。75.0%（97/129）的患者开始使用三唑类药物单药治疗。所有患者中，伏立康唑耐药病例的 6 周和 12 周死亡率均高于伏立康唑敏感病例（42.3%对 28.2%，P=0.20；57.7%对 36.9%，P=0.064）和非 ICU 患者（36.4%对 21.6%，P=0.16；54.4%对 30.7%，P=0.035）。6 周和 12 周时 ICU 患者的死亡率均非常高，与三唑类药物敏感性无关（75.0%对 66.7%，P=0.99；75.0%对 73.3%，P=0.99）。
在曲霉菌培养阳性的血液病患者中，伏立康唑耐药的比例非常高。与伏立康唑敏感的 IA 患者相比，非 ICU 患者中伏立康唑耐药的 IA 患者在 12 周时的总死亡率显著更高。
