Infectious Diseases Unit, Alfred Health, and Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia.
Lancet Infect Dis. 2013 Jun;13(6):519-28. doi: 10.1016/S1473-3099(13)70076-8. Epub 2013 Apr 30.
Empirical treatment with antifungal drugs is often used in haematology patients at high risk of invasive aspergillosis. We compared a standard diagnostic strategy (culture and histology) with a rapid biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) for directing the use of antifungal treatment in this group of patients.
In this open-label, parallel-group, randomised controlled trial, eligible patients were adults undergoing allogeneic stem-cell transplantation or chemotherapy for acute leukaemia, with no history of invasive fungal disease. Enrolled patients were randomly assigned (1:1) by a computer-generated schedule to follow either a standard diagnostic strategy (based on culture and histology) or a biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) to direct treatment with antifungal drugs. Patients, were followed up for 26 weeks or until death. Masking of the use of different diagnostic tests was not possible for patients, treating physicians, or investigators. The primary endpoint was empirical treatment with antifungal drugs in the 26 weeks after enrolment (for the biomarker-based diagnostic strategy, a single postive galactomannan or PCR result was deemed insufficient to confirm invasive aspergillosis, so treatment in this context was classified as empirical). This outcome was assessed by an independent data review committee from which the study allocations were masked. Analyses were by intention to treat and included all enrolled patients. This study is registered with ClinicalTrial.gov, number NCT00163722.
240 eligible patients were recruited from six Australian centres between Sept 30, 2005, and Nov 19, 2009. 122 were assigned the standard diagnostic strategy and 118 the biomarker-based diagnostic strategy. 39 patients (32%) in the standard diagnosis group and 18 (15%) in the biomarker diagnosis group received empirical antifungal treatment (difference 17%, 95% CI 4-26; p=0·002). The numbers of patients who had hepatotoxic and nephrotoxic effects did not differ significantly between the standard diagnosis and biomarker diagnosis groups (hepatotoxic effects: 21 [17%] vs 12 [10%], p=0·11; nephrotoxic effects: 52 [43%] vs 60 [51%], p=0·20).
Use of aspergillus galactomannan and PCR to direct treatment reduced use of empirical antifungal treatment. This approach is an effective strategy for the management of invasive aspergillosis in high-risk haematology patients.
Australian National Health and Medical Research Council, Cancer Council New South Wales, Pfizer, Merck, Gilead Sciences.
在罹患侵袭性曲霉菌病风险较高的血液病患者中，常采用经验性抗真菌药物治疗。我们对比了标准诊断策略（培养和组织学）与基于快速生物标志物的诊断策略（曲霉半乳甘露聚糖和 PCR），以指导此类患者使用抗真菌治疗。
这是一项开放标签、平行组、随机对照试验，纳入的合格患者为正在接受异基因造血干细胞移植或急性白血病化疗的成年人，且无侵袭性真菌感染病史。通过计算机生成的方案将入组患者（1:1）随机分配，分别遵循标准诊断策略（基于培养和组织学）或基于生物标志物的诊断策略（曲霉半乳甘露聚糖和 PCR），以指导抗真菌药物治疗。患者接受 26 周或直至死亡的随访。由于患者、治疗医生或研究者无法对不同诊断检测的使用情况进行设盲，因此无法对其进行设盲。主要终点为入组后 26 周的经验性抗真菌治疗（对于基于生物标志物的诊断策略，单次阳性的半乳甘露聚糖或 PCR 结果不足以确认侵袭性曲霉菌病，因此在这种情况下将治疗归类为经验性）。该结局由独立数据审查委员会评估，该委员会对研究分组情况设盲。分析为意向治疗分析，纳入所有入组患者。该研究在 ClinicalTrials.gov 注册，编号为 NCT00163722。
2005 年 9 月 30 日至 2009 年 11 月 19 日，6 家澳大利亚中心共纳入 240 名合格患者。122 名患者被分配至标准诊断组，118 名患者被分配至基于生物标志物的诊断组。标准诊断组中有 39 名（32%）患者接受了经验性抗真菌治疗，而基于生物标志物的诊断组中有 18 名（15%）患者接受了经验性抗真菌治疗（差异 17%，95%CI 4-26；p=0·002）。标准诊断组和基于生物标志物诊断组的肝毒性和肾毒性患者数量无显著差异（肝毒性：21 [17%] 例 vs 12 [10%] 例，p=0·11；肾毒性：52 [43%] 例 vs 60 [51%] 例，p=0·20）。
使用曲霉半乳甘露聚糖和 PCR 指导治疗可减少经验性抗真菌治疗的使用。这种方法是管理罹患侵袭性曲霉菌病的高风险血液病患者的有效策略。
澳大利亚国家卫生与医学研究理事会、新南威尔士州癌症委员会、辉瑞公司、默克公司、吉利德科学公司。
