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伊曲康唑长期治疗慢性肉芽肿病(CGD)患者以预防曲霉感染

[Long-term treatment of patients with itraconazole for the prevention of Aspergillus infections in patients with chronic granulomatous disease (CGD)].

作者信息

Petropoulou T, Liese J, Tintelnot K, Gahr M, Belohradsky B H

机构信息

Dr. von Haunersches Kinderspital, Ludwig-Maximilians-Universität München.

出版信息

Mycoses. 1994;37 Suppl 2:64-9.

PMID:7609746
Abstract

Chronic granulomatous disease (CGD) represents an innate immunodeficiency: the reduced production of oxygen radicals in phagocytosing cells results in decreased ability to kill pathogenic microorganisms. The patients concerned suffer from severe recurrent infections due to bacteria and fungi. Prophylactic administration of trimethoprim-sulfamethoxazole, as usual in CGD-patients, has markedly reduced the incidence of bacterial infections. Now as before, however, there is a high risk to become affected by invasive fungal infections, mainly due to Aspergillus spp. which often are lethal. Therefore, a well-compatible antimycotic long-term prophylaxis effective against Aspergillus would be attractive. In the present study the compatibility of the oral triazole itraconazole was tested in 8 CGD-patients with high risk of Aspergillus infections. Itraconazole was administered in capsules with a dosage of 5.1 mg/kg body weight per day on an average for a mean range of 23 months. Periodically liver enzymes, renal retention and electrolytes were assessed as well as itraconazole serum levels. Aspergillus serology tests included complement fixation tests, IgG-ELISA, precipitation tests, IgE determination and Aspergillus-RAST. During the prophylactic treatment in all of the 8 patients no gastrointestinal side effects or hypersensitivity reactions were observed. Renal retention and serum electrolytes as well as liver enzyme values were in normal ranges with all patients. Itraconazole serum levels showed a marked intra- and interindividual variability. However, 82% of the peak levels were in ranges regarded as therapeutically effective for itraconazole. Under prophylaxis a clear decrease of Aspergillus IgG-ELISA values was observed in 5 of 7 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

慢性肉芽肿病(CGD)是一种先天性免疫缺陷病:吞噬细胞中氧自由基生成减少导致杀灭致病微生物的能力下降。相关患者会遭受细菌和真菌感染引起的严重反复感染。像CGD患者通常那样预防性使用复方新诺明,已显著降低了细菌感染的发生率。然而,如今和以往一样,患者仍有很高的风险受到侵袭性真菌感染,主要是由曲霉菌属引起,这些感染往往是致命的。因此,一种对曲霉菌有效的、相容性良好的抗真菌长期预防措施将很有吸引力。在本研究中,对8名有曲霉菌感染高风险的CGD患者测试了口服三唑类药物伊曲康唑的相容性。伊曲康唑以胶囊形式给药,平均剂量为每天5.1毫克/千克体重,平均服用时间为23个月。定期评估肝酶、肾潴留和电解质以及伊曲康唑血清水平。曲霉菌血清学检测包括补体结合试验、IgG-ELISA、沉淀试验、IgE测定和曲霉菌-RAST。在所有8名患者的预防性治疗期间,未观察到胃肠道副作用或过敏反应。所有患者的肾潴留、血清电解质以及肝酶值均在正常范围内。伊曲康唑血清水平显示出明显的个体内和个体间差异。然而,82%的峰值水平处于被认为对伊曲康唑治疗有效的范围内。在预防期间,7名患者中有5名观察到曲霉菌IgG-ELISA值明显下降。(摘要截断于250字)

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