shumufeng
医师认证肿瘤综合科(医学生)
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Comparison of AmB-Based Induction Regimens for HIV-Associated Cryptococcal Meningitis
Cryptococcal meningitis (CM) is one of the leading causes of AIDS-related mortality in sub-Saharan Africa. The currently recommended therapy for CM is amphotericin B (AmB) plus 5-flucytosine (5-FC); however, 5-FC is not available in many resource-limited settings. Fluconazole is an attractive alternative to 5-FC because it is inexpensive and widely available, but its relative efficacy is still under evaluation. Now, data from a small randomized trial suggest that the two drugs might be comparable.
Eighty antiretroviral-naive HIV-infected patients in South Africa with their first episode of CM were randomized to receive one of four induction treatment regimens: AmB plus 5-FC, AmB plus fluconazole (at 600 mg twice daily or 800 mg daily), or AmB plus voriconazole (only patients who were not on rifampin were allowed in this group). After 2 weeks of induction therapy, all patients received fluconazole at 400 mg daily for 8 weeks and 200 mg daily thereafter. Elevated intracranial pressure was managed with serial lumbar punctures. Antiretroviral therapy was initiated 2 or more weeks after the start of antifungal treatment.
All the induction regimens had similar early fungicidal activity. Overall mortality was 12% at week 2 and 29% at week 10, with no significant differences among treatment groups. AmB-related anemia and nephrotoxicity were common, causing 10% of patients to discontinue therapy before 2 weeks. Serious toxicities related to use of 5-FC or fluconazole were uncommon.
Comment: This important study shows that in combination with AmB, high-dose fluconazole has similar early fungicidal activity as 5-FC and yields comparable outcomes. The study's main limitation is the small number of patients in each treatment group. A previous study found a trend toward improved early survival with high-dose fluconazole plus AmB compared with AmB alone (Clin Infect Dis 2009; 48:1775), although the results were not definitive. A phase III trial comparing AmB alone, AmB plus 5-FC, and AmB plus high-dose fluconazole is being conducted in Vietnam, and the results are eagerly awaited. In the interim, the findings of the current study support upcoming WHO guidelines recommending high-dose fluconazole plus AmB as induction therapy in resource-limited settings where 5-FC is not available.
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shumufeng edited on 2011-12-05 21:56
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王玉涛
医师认证血管外科(医学生)
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王玉涛
医师认证血管外科(医学生)
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Cryptococcal meningitis (CM) is one of the leading causes of AIDS-related mortality in sub-Saharan Africa. The currently recommended therapy for CM is amphotericin B (AmB) plus 5-flucytosine (5-FC); however,5-FC is not available in many resource-limited settings. Fluconazole is an attractive alternative to 5-FC because it is inexpensive and widely available, but its relative efficacy is still under evaluation. Now, data from a small randomized trial suggest that the two drugs might be comparable.
隐球菌脑膜炎是导致撒哈拉南部非洲地区艾滋病死亡的主要原因之一。目前推荐的隐球菌脑膜炎的治疗方法是男科霉素B和5氟胞嘧啶。但是，5氟胞嘧啶有限的资源环境中很难获得。氟康唑是一种引人注目的5氟胞嘧啶的替代物，因为氟康唑价格低廉并且容易获得，但它相关的功效仍有待评估。现在，一项随机对比试验的数据显示，这两种药物的功效大致相当。
Eighty antiretroviral-naive HIV-infected patients in South Africa with their first episode of CM were randomized to receive one of four induction treatment regimens: AmB plus 5-FC, AmB plus fluconazole (at 600 mg twice daily or 800 mg daily), or AmB plus voriconazole (only patients who were not on rifampin were allowed in this group). After 2 weeks of induction therapy, all patients received fluconazole at 400 mg daily for 8 weeks and 200 mg daily thereafter. Elevated intracranial pressure was managed with serial lumbar punctures. Antiretroviral therapy was initiated 2 or more weeks after the start of antifungal treatment.
八十例未经抗逆转录病毒治疗的南非地区伴有隐球菌脑膜炎首发病史的HIV感染者随机接受四种诱导实验方法中的一种：男科霉素B加5氟胞嘧啶；男科霉素B加氟康唑（600mg，一日两次或800mg，一日一次），男科霉素B加伏立康唑（只有没有使用利福平的患者才能允许加入本组）。在两个星期的诱导治疗后，所有患者每天服用400mg氟康唑，连续使用8个星期，之后剂量改为200mg，每天一次。通过连续腰椎穿刺以控制颅内压增高。抗逆转录病毒治疗在抗真菌治疗两周或更长时间后开始。
All the induction regimens had similar early fungicidal activity. Overall mortality was 12% at week 2 and 29% at week 10, with no significant differences among treatment groups. AmB-related anemia and nephrotoxicity were common, causing 10% of patients to discontinue therapy before 2 weeks. Serious toxicities related to use of 5-FC or fluconazole were uncommon.
所有的诱导疗法有相似的早期抑菌活性。第二周和第十周的总死亡率是12%和29%，治疗组没有显著差异。男科霉素B普遍引起的贫血和中毒性肾损害，导致10%的患者在前两周便中断治疗。应用5氟胞嘧啶或氟康唑引起的严重毒性反应并不常见。
Comment:This important study shows that in combination with AmB, high-dose fluconazole has similar early fungicidal activity as 5-FC and yields comparable outcomes. The study's main limitation is the small number of patients in each treatment group. A previous study found a trend toward improved early survival with high-dose fluconazole plus AmB compared with AmB alone (Clin Infect Dis 2009; 48:1775), although the results were not definitive. A phase III trial comparing AmB alone, AmB plus 5-FC, and AmB plus high-dose fluconazole is being conducted in Vietnam, and the results are eagerly awaited. In the interim, the findings of the current study support upcoming WHO guidelines recommending high-dose fluconazole plus AmB as induction therapy in resource-limited settings where 5-FC is not available.
评论：这项重要的研究表明，大剂量的氟康唑与男科霉素B联合应用具有和5氟胞嘧啶相似的早期抑菌活性并产生相近的治疗结果。这项研究的主要限制在于每个治疗组患者数量较少。之前的一项研究发现了联合应用大剂量氟康唑和男科霉素B比单独应用男科霉素B提高了早期生存率的趋势 (Clin Infect Dis 2009;48:1775)，尽管这项结果并没有权威性。一项单独应用男科霉素B，男科霉素B加5氟胞嘧啶以及男科霉素B加大剂量氟康唑的III期对比试验正在越南展开，研究的结果期待已久。在此期间，目前研究的结果支持即将出台的WHO关于在有限的资源环境中，5氟胞嘧啶难以获取的情况下应用大剂量氟康唑联合男科霉素B作为诱导治疗的指导方针。
