伊曲康唑治疗中枢神经系统真菌感染的临床开放研究

目的:观察伊曲康唑注射液和口服液序贯治疗中枢神经系统真菌感染的疗效,以及与两性霉素B和(或)氟胞嘧啶联合应用时的安全性。方法:采用开放性临床研究,自2004年6月-2005年9月间共收治17例中枢神经系统真菌感染,均采用伊曲康唑单独或联合两性霉素B和(或)氟胞嘧啶治疗,伊曲康唑注射液治疗至少1 wk以上。伊曲康唑注射液静脉滴注d 1～2为200 mg,q 12 h,d 3～14为200 mg·d-1;继之伊曲康唑口服液200 mg,q 12 h序贯治疗,两性霉素B 20～30 mg·d-1缓慢静脉滴注和(或)氟胞嘧啶6 g·d-1,分4次口服。结果:确诊病例14例,临床诊断病例3例,病原菌包括隐球菌、曲霉菌和小型无绿藻。2例治疗2 d死亡,未纳入疗效评估,临床总有效率为73％(11／15)。其中2例脑曲霉病、1例无绿藻脑膜炎、8例隐球菌脑膜炎(隐脑)均获痊愈;3例隐脑进步,1例侵袭性脑曲霉病无效死亡。治疗过程中,伊曲康唑注射液的不良反应主要为轻度肝功能异常,口服液治疗中部分病人有消化道症状,包括恶心、食欲下降,发生在服药2 mo以后。结论:伊曲康唑注射液和口服液单独或联合其他抗真菌药物治疗中枢神经系统真菌感染具有较好的疗效和安全性。

Itraconazole injection/oral solution therapy for central nervous system fungal infection: an open clinical study

AIM: To evaluate the efficacy of itraconazole injection and oral solution for the treatment of central nervous system ( CNS) fungal infection, and its safety in combination with amphotericin B, and/or flucytosine. METHODS: Seventeen patients admitted to our hospital with CNS fungal infection were enrolled in an open-label clinical trial from June 2004 to September 2005. They were treated with itraconazole alone or combined with amphotericine B, and/or flucytosine. In this study, patients were treated with itraconazole injection (d 1 - 2, 200 mg, q 12 h; d 3 - 14, 200 mg·d-1) for a minimum of 7 d were included in the efficacy eval- After treated with intraconazole injection, the patients were followed by administration of intraconazole oral solution, and/or in combination with amphotericine B slow intravenouse infusion or flucytosine taken orally. RESULTS: A total of 17 patients included definite (n = 14) or probable (n = 3) CNS fungal infection were enrolled. The identified fungi were Cryptococcus neoformans, Aspergillus spp., and Prototheca wickerhamii. All the patients had headache, fever, and higher than 300 mmH2O intracranial pressure, including 7 patients with underlying diseases, 7 patients with complication of coma and 10 patients with cerebral herniation. Six patients underwent Ommaya-reservoir and ventricular shunt operations. Overall, two patients died at 2 d after the therapy excluding from the efficacy evaluation. The rest 15 patients included 11 (11/15, 73%) with excellent response to this remedy consisting of one with cerebral aspergilloma, one with aspergillus meningitis, one with prototheca wickerhamii meningitis, two with cerebral cryptococcoma, and six with cryptococcal meningitis, only three of them were treated with itraconazole alone. Three patients with cryptococcal meningitis showed partial response and one failed. All patients tolerated well with itraconazole. The adverse reactions including only 2 of mild liver function disorder probably due to intravenous administration and 3 of mild to moderate nausea, loss of appetite after oral intake more than 2 mo. CONCLUSION: Itraconazole injection and oral solution show impressive curing activity on CNS fungal infection together with safety on either itraconazole alone or combined with other antifungal drugs (amphotericine B, and/or flucytosine) .