Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M. D. Anderson Cancer Center, University of Houston, Houston, TX 77030, USA.
Clin Infect Dis. 2010 Feb 1;50(3):405-15. doi: 10.1086/649879.
Invasive fungal infections (IFIs) remain an important cause of morbidity and mortality in patients with acute or chronic leukemia. Advances in the pharmacotherapy of fungal infections and a shift in the epidemiological characteristics of fungal pathogens toward fluconazole-resistant Candida species and saprophytic molds have placed a greater emphasis on selection of broader-spectrum agents for empirical therapy of IFIs in this high-risk population. Newer diagnostic modalities, such as the Aspergillus galactomannan test, the 1,3-beta-d-glucan test, and polymerase chain reaction detection of fungal DNA, may facilitate the earlier diagnosis of IFIs, but their role in detecting breakthrough infection and their usefulness as a marker to withhold antifungal therapy in high-risk leukemia patients with IFI are less obvious, especially in patients who are receiving antifungal prophylaxis. Only 2 strategies have been shown in prospective studies to improve survival from mold infection in patients with acute myelogenous leukemia or myelodysplastic syndrome: (1) preemptive initiation of antifungal therapy at first sign of invasive aspergillosis on computed tomography (CT) scan and (2) antifungal prophylaxis with posaconazole. CT-guided treatment decisions are more complex in patients with advanced leukemia, however, because of concomitant infection or relapsing malignancy. Similarly, posaconazole is often not a viable prophylaxis or treatment option in patients with poor oral intake, gastrointestinal dysfunction, or possible drug interaction (eg, proton pump inhibitor prophylaxis in patients on high-dose glucocorticosteroids). As a result, the management of IFI in patients with leukemia demands an individualized treatment plan.
侵袭性真菌感染（IFI）仍然是急性或慢性白血病患者发病率和死亡率的重要原因。抗真菌药物治疗的进步以及真菌病原体的流行病学特征向氟康唑耐药念珠菌属和腐生性霉菌的转变，使得在这种高危人群中，对IFI 的经验性治疗选择更广泛的谱的药物变得更加重要。新的诊断方法，如曲霉半乳甘露聚糖试验、1,3-β-d-葡聚糖试验和真菌 DNA 的聚合酶链反应检测，可能有助于更早地诊断 IFI，但它们在检测突破性感染中的作用及其作为高危白血病患者 IFI 中停止抗真菌治疗的标志物的有用性并不明显，尤其是在接受抗真菌预防的患者中。只有 2 种策略在前瞻性研究中显示可改善急性髓细胞白血病或骨髓增生异常综合征患者的霉菌感染生存率：（1）在 CT 扫描上出现侵袭性曲霉菌病的第一迹象时，抢先开始抗真菌治疗；（2）使用泊沙康唑进行抗真菌预防。然而，对于晚期白血病患者，CT 引导的治疗决策更加复杂，因为存在合并感染或复发性恶性肿瘤。同样，泊沙康唑在口服摄入不良、胃肠功能障碍或可能存在药物相互作用的患者（例如，接受大剂量糖皮质激素治疗的患者使用质子泵抑制剂预防）中，通常不是可行的预防或治疗选择。因此，白血病患者的 IFI 管理需要个体化的治疗计划。
