Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study
Voriconazole Resistance and Mortality in Invasive Aspergillosis: A Multicenter Retrospective Cohort Study
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DOI：
10.1093/cid/ciy859
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发表时间：
2019-05-01
影响因子：
11.8
通讯作者：
Verweij, Paul E.
中科院分区：
文献类型：
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作者：
Lestrade, Pieter P.;Bentvelsen, Robbert G.;Verweij, Paul E.
背景三唑耐药是侵袭性曲霉病（IA）的一个日益严重的问题。小病例系列显示，感染三唑耐药烟曲霉的患者死亡率为50%-100%，但与三唑敏感IA的直接比较缺乏。进行了一项5年回顾性队列研究（2011-2015），以比较伏立康唑敏感和伏立康唑耐药IA患者的死亡率。对烟曲霉菌培养阳性患者进行调查，以确定确诊、可能和推定IA患者。研究患者的临床特征、第42天和第90天的死亡率、三唑类药物耐药性和抗真菌治疗。在196例IA患者中，37例（19%）患有伏立康唑耐药感染。103例（53%）患者的基础疾病为血液恶性肿瘤，154例（79%）患者开始接受伏立康唑治疗。与伏立康唑敏感病例相比，伏立康唑耐药与第42天总死亡率增加21%（49% vs 28%; P = 0.017）和第90天总死亡率增加25%（62% vs 37%; P = 0.0038）相关。在非重症监护室患者中，伏立康唑耐药病例在第42天的生存率降低了19%（P = 0.045）。接受适当初始伏立康唑治疗的患者的死亡率为24%，而接受不适当治疗的患者的死亡率为47%（P = 0.016），尽管在中位数10天后转换为适当的抗真菌治疗。伏立康唑耐药与IA患者第42天和第90天的21%和25%的额外总体死亡率相关。延迟开始适当的抗真菌治疗与总死亡率增加相关。
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.