Menichetti Francesco
Infectious Diseases Unit, Cisanello Hospital, Pisa, Italy.
Clin Infect Dis. 2004 Oct 15;39 Suppl 4:S181-4. doi: 10.1086/421954.
The risk for invasive fungal infections in patients with acute leukemia is generally low (4%-8%), and the routine use of fungal prophylaxis is not warranted except in specific high-risk groups that should be identified among this population. In a prophylactic study with a new agent, fluconazole or itraconazole oral solution represent good choices for the comparator because they are proven better than placebo or oral nonabsorbable antifungal agents in reducing the risk of invasive fungal infections in patients with acute leukemia. Because prophylaxis is most valuable when the risk of infection is high, patients with well-understood risk factors (severe mucosal disruption caused by chemotherapy, impaired cell-mediated immunity caused by steroids or fludarabine, use of a central venous catheter, and colonization by Candida species) should be selected. The end points for antifungal prophylactic trials should focus on proven and probable invasive fungal infections. Superficial and mucosal fungal infections do not represent a primary end point for these studies. Poor compliance should be considered as an interruption of treatment due to side effects and should be included in the criteria for failure. Fungus-related mortality should be evaluated as a failure of prophylaxis, whereas overall mortality may be influenced by many other cofactors. Differences in gastrointestinal toxicity of antifungal agents may limit the use of double-blind designs in some situations.
急性白血病患者发生侵袭性真菌感染的风险通常较低（4%-8%），除了应在该人群中识别出的特定高危组外，一般无需常规使用真菌预防措施。在一项使用新药物的预防性研究中，氟康唑或伊曲康唑口服溶液是比较的良好选择，因为它们在降低急性白血病患者侵袭性真菌感染风险方面已被证明优于安慰剂或口服不吸收的抗真菌药物。由于在感染风险高时预防最为有效，所以应选择具有明确风险因素（化疗导致严重黏膜破坏、类固醇或氟达拉滨导致细胞介导免疫受损、使用中心静脉导管以及念珠菌属定植）的患者。抗真菌预防试验的终点应聚焦于已证实和可能的侵袭性真菌感染。浅表和黏膜真菌感染并非这些研究的主要终点。依从性差应被视为因副作用导致的治疗中断，并应纳入失败标准。真菌相关死亡率应作为预防失败进行评估，而总死亡率可能受许多其他因素影响。抗真菌药物在胃肠道毒性方面的差异可能会在某些情况下限制双盲设计的使用。
