Itraconazole to prevent fungal infections in chronic granulomatous disease
Itraconazole to prevent fungal infections in chronic granulomatous disease
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DOI：
10.1056/nejmoa021931
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发表时间：
2003-06-12
影响因子：
158.5
通讯作者：
Holland, SM
中科院分区：
文献类型：
--
作者：
Gallin, JI;Alling, DW;Holland, SM
背景：慢性肉芽肿病是一种罕见的疾病，其中吞噬细胞无法产生过氧化氢。患者容易受到细菌和真菌感染。预防性抗生素和γ干扰素减少了细菌感染，但也存在危及生命的真菌感染的危险。我们评估了伊曲康唑预防慢性肉芽肿病严重真菌感染的功效。方法：39 名 5 岁以上患者（6 名女性和 33 名男性；平均年龄 14.9 岁）参加了一项随机、双盲、安慰剂对照研究。在最初分配的治疗后，每位患者每年交替使用伊曲康唑和安慰剂。 13岁或以上的患者以及所有体重至少50公斤的患者每天接受单剂量200毫克伊曲康唑； 13岁以下或体重50公斤以下的儿童每天单剂100毫克。主要终点是严重真菌感染，由组织学结果或培养确定。结果：一名患者（不符合治疗依从性）在接受伊曲康唑治疗时出现严重真菌感染，而接受安慰剂时有七名患者出现严重真菌感染（P=0.10）。没有接受伊曲康唑的患者出现浅表真菌感染，但有五名接受安慰剂的患者出现浅表真菌感染。尽管一名患者出现皮疹，另一名患者的肝功能检查结果升高，但没有发现严重的毒性反应；停用伊曲康唑后，这两种效应都会得到缓解。结论：伊曲康唑预防似乎是一种有效且耐受性良好的治疗方法，可降低慢性肉芽肿性疾病中真菌感染的频率，但有必要监测长期毒性作用。
Background: Chronic granulomatous disease is a rare disorder in which the phagocytes fail to produce hydrogen peroxide. The patients are predisposed to bacterial and fungal infections. Prophylactic antibiotics and interferon gamma have reduced bacterial infections, but there is also the danger of life-threatening fungal infections. We assessed the efficacy of itraconazole as prophylaxis against serious fungal infections in chronic granulomatous disease.Methods: Thirty-nine patients at least 5 years old (6 female and 33 male; mean age, 14.9 years) were enrolled in a randomized, double-blind, placebo-controlled study. After the initially assigned treatment, each patient alternated between itraconazole and placebo annually. Patients 13 years of age or older and all patients weighing at least 50 kg received a single dose of 200 mg of itraconazole per day; those less than 13 years old or weighing less than 50 kg received a single dose of 100 mg per day. The primary end point was severe fungal infection, as determined by histologic results or culture.Results: One patient (who had not been compliant with the treatment) had a serious fungal infection while receiving itraconazole, as compared with seven who had a serious fungal infection while receiving placebo (P=0.10). No patient receiving itraconazole but five patients receiving placebo had a superficial fungal infection. No serious toxic effects were noted, although one patient had a rash and another had elevated results on liver-function tests; both of these effects resolved with the discontinuation of itraconazole.Conclusions: Itraconazole prophylaxis appears to be an effective and well-tolerated treatment that reduces the frequency of fungal infections in chronic granulomatous disease, but monitoring for long-term toxic effects is warranted.