Stevens D A, Kan V L, Judson M A, Morrison V A, Dummer S, Denning D W, Bennett J E, Walsh T J, Patterson T F, Pankey G A
Dept. of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128-2699, USA.
Clin Infect Dis. 2000 Apr;30(4):696-709. doi: 10.1086/313756. Epub 2000 Apr 20.
Aspergillosis comprises a variety of manifestations of infection. These guidelines are directed to 3 principal entities: invasive aspergillosis, involving several organ systems (particularly pulmonary disease); pulmonary aspergilloma; and allergic bronchopulmonary aspergillosis. The recommendations are distilled in this summary, but the reader is encouraged to review the more extensive discussions in subsequent sections, which show the strength of the recommendations and the quality of the evidence, and the original publications cited in detail. Invasive aspergillosis. Because it is highly lethal in the immunocompromised host, even in the face of therapy, work-up must be prompt and aggressive, and therapy may need to be initiated upon suspicion of the diagnosis, without definitive proof (BIII). Intravenous therapy should be used initially in rapidly progressing disease (BIII). The largest therapeutic experience is with amphotericin B deoxycholate, which should be given at maximum tolerated doses (e.g., 1-1.5 mg/kg/d) and should be continued, despite modest increases in serum creatinine levels (BIII). Lipid formulations of amphotericin are indicated for the patient who has impaired renal function or who develops nephrotoxicity while receiving deoxycholate amphotericin (AII). Oral itraconazole is an alternative for patients who can take oral medication, are likely to be adherent, can be demonstrated (by serum level monitoring) to absorb the drug, and lack the potential for interaction with other drugs (BII). Oral itraconazole is attractive for continuing therapy in the patient who responds to initial iv therapy (CIII). Therapy should be prolonged beyond resolution of disease and reversible underlying predispositions (BIII). Adjunctive therapy (particularly surgery and combination chemotherapy, also immunotherapy), may be useful in certain situations (CIII). Aspergilloma. The optimal treatment strategy for aspergilloma is unknown. Therapy is predominantly directed at preventing life-threatening hemoptysis. Surgical removal of aspergilloma is definitive treatment, but because of significant morbidity and mortality it should be reserved for high-risk patients such as those with episodes of life-threatening hemoptysis, and considered for patients with underlying sarcoidosis, immunocompromised patients, and those with increasing Aspergillus-specific IgG titers (CIII). Surgical candidates would need to have adequate pulmonary function to undergo the operation. Bronchial artery embolization rarely produces a permanent success, but may be useful as a temporizing procedure in patients with life-threatening hemoptysis. Endobronchial and intracavitary instillation of antifungals or oral itraconazole may be useful for this condition. Since the majority of aspergillomas do not cause life-threatening hemoptysis, the morbidity and cost of treatment must be weighed against the clinical benefit. Allergic bronchopulmonary aspergillosis (APBA). Although no well-designed studies have been carried out, the available data support the use of corticosteroids for acute exacerbations of ABPA (AII). Neither the optimal corticosteroid dose nor the duration of therapy has been standardized, but limited data suggest the starting dose should be approximately 0.5 mg/kg/d of prednisone. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). The available data suggest that clinical symptoms alone are inadequate to make such decisions, since significant lung damage may occur in asymptomatic patients. Increasing serum IgE levels, new or worsening infiltrate on chest radiograph, and worsening spirometry suggest that corticosteroids should be used (BII). Multiple asthmatic exacerbations in a patient with ABPA suggest that chronic corticosteroid therapy should be used (BIII). Itraconazole appears useful as a corticosteroid sparing agent (BII). (ABSTRACT TRUNCATED)
曲霉病包括多种感染表现形式。本指南针对3种主要病症:侵袭性曲霉病,累及多个器官系统(尤其是肺部疾病);肺曲菌球;以及变应性支气管肺曲霉病。本摘要提炼了相关建议,但鼓励读者查阅后续章节中更详尽的讨论内容,其中展示了建议的力度、证据的质量以及详细引用的原始文献。侵袭性曲霉病。由于其在免疫功能低下宿主中具有高度致死性,即便接受治疗,检查工作也必须迅速且积极,在怀疑诊断时可能就需开始治疗,而无需确凿证据(BIII级)。对于病情迅速进展的患者,初始应采用静脉治疗(BIII级)。治疗经验最多的是使用脱氧胆酸盐两性霉素B,应给予最大耐受剂量(如1 - 1.5mg/kg/日),即便血清肌酐水平略有升高也应继续使用(BIII级)。两性霉素的脂质制剂适用于肾功能受损或在接受脱氧胆酸盐两性霉素治疗时出现肾毒性的患者(AII级)。口服伊曲康唑适用于能够口服药物、可能依从治疗、可通过血清水平监测证明能吸收药物且不存在与其他药物相互作用可能性的患者(BII级)。口服伊曲康唑对于初始静脉治疗有反应的患者用于持续治疗很有吸引力(CIII级)。治疗应延长至疾病缓解且可逆的潜在易患因素消除之后(BIII级)。辅助治疗(尤其是手术、联合化疗以及免疫治疗)在某些情况下可能有用(CIII级)。肺曲菌球。肺曲菌球的最佳治疗策略尚不清楚。治疗主要针对预防危及生命的咯血。手术切除肺曲菌球是确定性治疗方法,但由于存在显著的发病率和死亡率,应仅用于高危患者,如出现危及生命咯血发作的患者,对于患有潜在结节病的患者、免疫功能低下患者以及曲霉特异性IgG滴度升高的患者可考虑手术(CIII级)。手术候选者需要有足够的肺功能才能进行手术。支气管动脉栓塞很少能取得永久性成功,但对于有危及生命咯血的患者可能作为一种临时措施有用。支气管内和腔内注入抗真菌药物或口服伊曲康唑对此病症可能有用。由于大多数肺曲菌球不会导致危及生命的咯血,必须权衡治疗的发病率和费用与临床益处。变应性支气管肺曲霉病(ABPA)。尽管尚未开展精心设计的研究,但现有数据支持在ABPA急性加重期使用皮质类固醇(AII级)。皮质类固醇的最佳剂量和治疗持续时间均未标准化,但有限的数据表明起始剂量应为泼尼松约0.5mg/kg/日。是否逐渐减少皮质类固醇剂量应根据个体情况决定,取决于临床病程(BIII级)。现有数据表明仅依据临床症状不足以做出此类决定,因为无症状患者也可能发生严重的肺损伤。血清IgE水平升高、胸部X线片上新发或加重的浸润以及肺功能测定恶化提示应使用皮质类固醇(BII级)。ABPA患者多次哮喘加重提示应使用慢性皮质类固醇治疗(BIII级)。伊曲康唑似乎作为一种皮质类固醇节省剂有用(BII级)。(摘要截选)