Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia
Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia
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DOI：
10.1056/nejmoa040446
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发表时间：
2004-09-30
影响因子：
158.5
通讯作者：
dePauw, BE
中科院分区：
文献类型：
--
作者：
Walsh, TJ;Teppler, H;dePauw, BE
背景：持续发热和中性粒细胞减少的患者通常接受常规或脂质体阿替霉素B的经验性治疗，以预防和早期治疗侵袭性真菌感染。卡泊芬净是新型棘白菌素类化合物的一员，可能是一种有效的替代品，比两性霉素B耐受性更好。方法：在这项随机、双盲、跨国试验中，我们评估了卡泊芬净的疗效和安全性与脂质体相比两性霉素B作为经验性抗真菌治疗。在进入研究时，根据风险和既往是否接受过抗真菌预防对患者进行分层。一个成功的结果被定义为履行所有组成部分的五部分复合endpoint.Results：疗效进行了评估，在1095例（556接受卡泊芬净和539接受脂质体阿替霉素B）。调整分层后，卡泊芬净的总体成功率为33.9%，脂质体阿替霉素B为33.7%（差异的95.2%置信区间为-5.6%至6.0%），符合卡泊芬净非劣效性的统计学标准。在基线真菌感染的患者中，卡泊芬净治疗成功的比例较高（51.9% vs. 25.9%，P=0.04）。卡泊芬净组治疗后至少存活7天的患者比例更高（92.6% vs. 89.2%，P=0.05）。卡泊芬净组提前终止研究的发生率低于阿替霉素B组（10.3% vs. 14.5%，P=0.03）。在中性粒细胞减少症期间，两组的突破性真菌感染率和发热消退率相似。接受卡泊芬净治疗的患者中持续肾毒性作用的患者较少（2.6%对11.5%，P
BACKGROUND:Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B.METHODS:In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point.RESULTS:Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, -5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P