Efficacy and safety of high-dose fluconazole in the initial treatment of non-human immunodeficiency virus-related cryptococcal meningitis

中华传染病杂志 Pub Date : 2019-11-15 DOI:10.3760/CMA.J.ISSN.1000-6680.2019.11.003

Jia-Hui Cheng, Li-ping Huang, Jingyun Ye, Chun-Xing Que, Sen Wang, Jie Yu, Yuanyuan Liu, Hua-zhen Zhao, Li-Ping Zhu

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Abstract

Objective To evaluate the efficacy and safety of high-dose fluconazole alone or combined with flucytosine as initial therapy for cryptococcal meningitis (CM) in non-human immunodeficiency virus (HIV)-related patients. Methods Twenty-five non-HIV-infected patients with CM from June 2015 to September 2018 in Huashan Hospital, Fudan University, who were initially treated with high-dose fluconazole with or without flucytosine for at least seven days were retrospectively reviewed.Clinical features and antifungal (600-800 mg/d) regimens were recorded, clinical responses and drug-related adverse events were evaluated. Mann-Whitney test and Fisher′s exact probabilities test were applied to compare variables between groups. Results Of the 25 patients enrolled in this study, 15 had predisposing factors. Headache (25 cases), fever (21 cases), vomiting (13 cases) and neck stiffness (13 cases) were common manifestations. Abnormalities of cranial computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were found in 22 cases.Nineteen patients were treated with high-dose fluconazole plus flucytosine for initial therapy, and six patients were treated with high-dose fluconazole alone. The course of initial regimens with high-dose fluconazole was 42 (29, 120) days. At the end of initial therapy, partial response in 20 patients, stable response in three patients and death in two patients were observed, and the overall effective rate was 80%(20/25). In treatment failure group of initial treatment, the proportion of patients with baseline cerebrospinal fluid opening pressure over 300 mmH2O (1 mmH2O=0.009 8 kPa) and with altered mental status were both significantly higher compared with those in treatment success group. Fluconazole related adverse drug events were observed including elevated transaminases (one case), gastrointestinal symptoms combined with hypokalemia (two cases), and systemic rash (three cases). Except for three patients with rash reduced the dosage of fluconazole, no other patients were given dosage adjustment. Conclusion High-dose fluconazole alone or combined with flucytosine is effective and safe for the initial therapy of non-HIV-related CM patients. Key words: Meningitis, cryptococcal; Fluconazole; Initial therapy; High-dose

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大剂量氟康唑初始治疗非人类免疫缺陷病毒相关隐球菌性脑膜炎的疗效和安全性

目的评价大剂量氟康唑单独或联合氟胞嘧啶治疗非人类免疫缺陷病毒（HIV）相关患者隐球菌性脑膜炎（CM）的疗效和安全性。方法回顾性分析2015年6月至2018年9月在复旦大学华山医院接受大剂量氟康唑联合或不联合氟胞嘧啶治疗至少7天的非HIV感染CM患者25例。记录临床特征和抗真菌（600-800 mg/d）方案，评估临床反应和药物相关不良事件。采用Mann-Whitney检验和Fisher精确概率检验对各组变量进行比较。结果在本研究的25名患者中，有15名患者有诱发因素。常见表现为头痛（25例）、发热（21例）、呕吐（13例）和颈部僵硬（13例。在22例病例中发现了颅骨计算机断层扫描（CT）和/或磁共振成像（MRI）异常。19例患者接受了大剂量氟康唑加氟胞嘧啶的初步治疗，6例患者接受大剂量氟唑单独治疗。大剂量氟康唑的初始治疗方案为42（29120）天。在初始治疗结束时，观察到20名患者出现部分反应，3名患者出现稳定反应，2名患者死亡，总有效率为80%（20/25）。在初次治疗的治疗失败组中，基线脑脊液开放压力超过300mmH2O（1mmH2O=0.009 8kPa）和精神状态改变的患者比例均显著高于治疗成功组。观察到与氟康唑相关的药物不良事件，包括转氨酶升高（1例）、胃肠道症状合并低钾血症（2例）和全身皮疹（3例）。除了3例皮疹患者减少了氟康唑的剂量外，其他患者均未进行剂量调整。结论大剂量氟康唑单独或联合氟胞嘧啶治疗非HIV相关CM患者是安全有效的。关键词：脑膜炎，隐球菌；氟康唑；初始治疗；高剂量

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中华传染病杂志

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5280

期刊介绍： The Chinese Journal of Infectious Diseases was founded in February 1983. It is an academic journal on infectious diseases supervised by the China Association for Science and Technology, sponsored by the Chinese Medical Association, and hosted by the Shanghai Medical Association. The journal targets infectious disease physicians as its main readers, taking into account physicians of other interdisciplinary disciplines, and timely reports on leading scientific research results and clinical diagnosis and treatment experience in the field of infectious diseases, as well as basic theoretical research that has a guiding role in the clinical practice of infectious diseases and is closely integrated with the actual clinical practice of infectious diseases. Columns include reviews (including editor-in-chief reviews), expert lectures, consensus and guidelines (including interpretations), monographs, short monographs, academic debates, epidemic news, international dynamics, case reports, reviews, lectures, meeting minutes, etc.