Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome
Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome
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DOI：
10.1016/s0002-9343(97)00151-4
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发表时间：
1997-09-01
影响因子：
5.9
通讯作者：
Powderly, W
中科院分区：
文献类型：
--
作者：
Wheat, J;MaWhinney, S;Powderly, W
目得：本研究评估了氟康唑治疗获得性免疫缺陷综合征（AIDS）和轻度至中度严重的表现播散性组织胞浆菌病的患者的疗效和安全性。患者和方法：这是一项多中心，开放标签，非随机前瞻性试验。所有患者均患有艾滋病和播散性组织胞浆菌病。患者在第一天口服1，200 mg氟康唑，然后每天口服600 mg氟康唑，持续8周，然后临床改善的患者接受氟康唑维持治疗，每天口服200 mg氟康唑，持续至少1年。中期分析显示失败率很高（10/20，50%），导致修订的协议，增加氟康唑剂量1,600毫克给药一次，第一天，然后800毫克，每天一次，持续时间为12周的诱导治疗，然后400毫克，每天1年的维持治疗。（74%; 95%置信区间[CI]：59%至85%），有轻度至中度重度临床表现，进入修订后的研究，每天800 mg氟康唑作为诱导治疗，持续12周。7例因组织胞浆菌病进展而诱导治疗失败的患者中，1例死于感染。在36名进入研究维持期的患者中，每天接受400 mg氟康唑治疗1年，11名（30.5%）复发，包括1名死亡（2.8%）。49例患者中有2例（4.1%）因4级不良事件而被排除，其中1例为碱性磷酸酶升高，另1例为天冬氨酸转氨酶升高。在1年的无复发率为53%（95%CI：32%至89%），促使关闭的study.CONCLUSIONS：氟康唑800毫克，每天是一个安全和中度有效的诱导治疗轻度或中度严重的播散性组织胞浆菌病的艾滋病患者。在历史比较的基础上，氟康唑400 mg/d的效果低于伊曲康唑200 - 400 mg/d或阿替霉素B 50 mg/周作为维持治疗预防复发。(C)1997年，Excerpta Medica，Inc.
PURPOSE: This study assesses the efficacy and safety of fluconazole therapy in patients with acquired immunodeficiency syndrome (AIDS) and mild to moderately severe manifestations of disseminated histoplasmosis.PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial. All patients had AIDS and disseminated histoplasmosis. Patients were treated with 1,200 mg of fluconazole given by mouth once on the first day, then 600 mg once daily for 8 weeks, and those patients who improved clinically were then assigned fluconazole maintenance therapy 200 mg once daily for at least 1 year. Interim analysis revealed a high failure rate (10 of 20, 50%), causing revision of the protocol to increase the fluconazole dose to 1,600 mg given once on the first day, then 800 mg once daily, and the duration to 12 weeks for induction therapy and then 400 mg daily for 1 year for maintenance therapy.MEASUREMENTS AND MAIN RESULTS: Thirty-six of 49 patients (74%; 95% confidence interval [CI]: 59% to 85%) with mild to moderately severe clinical manifestations who entered into the revised study responded to 800 mg of fluconazole daily for 12 weeks as induction therapy. Of the seven patients who failed induction therapy because of progression of histoplasmosis, one died of the infection. Of 36 patients who entered into the maintenance phase of the study receiving 400 mg of fluconazole daily for 1 year, 11 (30.5%) relapsed, including one who died (2.8%). Two of the 49 patients (4.1%) were removed because of grade 4 adverse events, alkaline phosphatase elevation for one and aspartate aminotransferase elevation in the other. The relapse-free rate at 1 year was 53% (95% CI: 32% to 89%), prompting closure of the study.CONCLUSIONS: Fluconazole 800 mg daily is a safe and moderately effective induction therapy for mild or moderately severe disseminated histoplasmosis in patients with AIDS. On the basis of historic comparison, fluconazole 400 mg daily is less effective than itraconazole 200 to 400 mg daily or amphotericin B 50 mg given weekly as maintenance therapy to prevent relapse. (C) 1997 by Excerpta Medica, Inc.