Morrissey C O, Gilroy N M, Macesic N, Walker P, Ananda-Rajah M, May M, Heath C H, Grigg A, Bardy P G, Kwan J, Kirsa S W, Slavin M, Gottlieb T, Chen S
Department of Infectious Diseases, Alfred Health and Monash University, Prahran, Victoria; Department of Clinical Haematology, Alfred Health, Prahran, Victoria.
Intern Med J. 2014 Dec;44(12b):1298-314. doi: 10.1111/imj.12596.
Invasive fungal disease (IFD) causes significant morbidity and mortality in patients undergoing allogeneic haemopoietic stem cell transplantation or chemotherapy for haematological malignancy. Much of these adverse outcomes are due to the limited ability of traditional diagnostic tests (i.e. culture and histology) to make an early and accurate diagnosis. As persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients despite broad-spectrum antibiotics have been associated with the development of IFD, most centres have traditionally administered empiric antifungal therapy (EAFT) to patients with PFUO. However, use of an EAFT strategy has not been shown to have an overall survival benefit and is associated with excessive antifungal therapy use. As a result, the focus has shifted to developing more sensitive and specific diagnostic tests for early and more targeted antifungal treatment. These tests, including the galactomannan enzyme-linked immunosorbent assay and Aspergillus polymerase chain reaction (PCR), have enabled the development of diagnostic-driven antifungal treatment (DDAT) strategies, which have been shown to be safe and feasible, reducing antifungal usage. In addition, the development of effective antifungal prophylactic strategies has changed the landscape in terms of the incidence and types of IFD that clinicians have encountered. In this review, we examine the current role of EAFT and provide up-to-date data on the newer diagnostic tests and algorithms available for use in EAFT and DDAT strategies, within the context of patient risk and type of antifungal prophylaxis used.
侵袭性真菌病(IFD)在接受异基因造血干细胞移植或因血液系统恶性肿瘤接受化疗的患者中可导致显著的发病率和死亡率。这些不良后果大多归因于传统诊断测试(即培养和组织学检查)早期准确诊断能力的有限性。由于中性粒细胞减少患者在使用广谱抗生素后仍持续或反复出现不明原因发热(PFUO)与IFD的发生相关,大多数中心传统上会对PFUO患者进行经验性抗真菌治疗(EAFT)。然而,EAFT策略尚未显示出对总体生存有益,且与过度使用抗真菌治疗相关。因此,重点已转向开发更敏感、特异的诊断测试,以实现早期且更具针对性的抗真菌治疗。这些测试,包括半乳甘露聚糖酶联免疫吸附测定和曲霉聚合酶链反应(PCR),促成了诊断驱动的抗真菌治疗(DDAT)策略的发展,该策略已被证明是安全可行的,可减少抗真菌药物的使用。此外,有效的抗真菌预防策略的发展改变了临床医生所遇到的IFD的发病率和类型情况。在本综述中,我们探讨了EAFT的当前作用,并在患者风险和所采用的抗真菌预防类型的背景下,提供有关可用于EAFT和DDAT策略的更新诊断测试及算法的最新数据。