Background

Cryptococcal meningitis remains a common cause of mortality in low- and middle-income countries, where amphotericin B deoxycholate (amphotericin) plus fluconazole is the most common treatment. Flucytosine is almost uniformly absent as is outcome data on flucytosine use in routine care. The main goal of this study was identified the cumulative mortality at 2, 4, and 10 weeks after hospital admission.

Methods

We conducted a retrospective, observational cohort study among HIV-infected adults with cryptococcal meningitis receiving amphotericin plus flucytosine as induction therapy in Brazil. We assessed cumulative mortality at 2, 4, and 10 weeks and the cumulative proportion discontinuating amphotericin or flucytosine due to toxicity at 2 weeks. We performed multiple logistic regression to identify variables associated with in-hospital mortality.

Results

In total, 77 individuals (n = 66 men) were included with median baseline CD4 of 29 (IQR, 9–68) cells/mcL. Twenty (26%) had at least one concurrent neurological disease diagnosed. Sixty (78%) patients received at least 14 days of amphotericin plus flucytosine. Cumulative mortality was 5% (4/77) at 2 weeks, 8% (6/77) at 4 weeks, and 19% (15/77) at 10 weeks. Cumulative proportion of patients that discontinuated amphotericin or flucytosine due to toxicity was 20% (16/77) at 2 weeks. In addition, in-hospital mortality was associated with receiving ≤ 10 days of induction therapy (odds ratio = 4.5, 95% CI 1.2–17.1, P = 0.028) or positive cerebrospinal fluid fungal culture after 2 weeks (odds ratio = 3.8, 95% CI 1.1–13.5, P = 0.035).

Conclusion

In this “real-world” study, amphotericin plus flucytosine shows low early mortality of patients with HIV-associated cryptococcal meningitis. Early discontinuation due to adverse events was moderate. More effective and safe antifungals are needed in order to improve the outcome of cryptococcal meningitis.

中文翻译：

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巴西圣保罗转诊中心在常规护理条件下接受两性霉素 B 脱氧胆酸盐加氟胞嘧啶治疗的 HIV 相关隐球菌脑膜炎患者

背景

隐球菌性脑膜炎仍然是低收入和中等收入国家的常见死亡原因，其中两性霉素 B 脱氧胆酸盐（两性霉素）加氟康唑是最常见的治疗方法。氟胞嘧啶几乎一律不存在，常规护理中使用氟胞嘧啶的结果数据也是如此。本研究的主要目标是确定入院后 2、4 和 10 周的累积死亡率。

方法

我们在巴西对接受两性霉素加氟胞嘧啶作为诱导治疗的 HIV 感染隐球菌脑膜炎成人进行了一项回顾性、观察性队列研究。我们评估了第 2、4 和 10 周的累积死亡率，以及第 2 周因毒性而停用两性霉素或氟胞嘧啶的累积比例。我们进行了多元逻辑回归来确定与院内死亡率相关的变量。

结果

总共包括 77 个个体（n  = 66 个男性），其中位基线 CD4 为 29（IQR，9-68）个细胞/mcL。20 人 (26%) 诊断出至少一种并发神经系统疾病。60 (78%) 名患者接受了至少 14 天的两性霉素加氟胞嘧啶。2 周时的累积死亡率为 5% (4/77)，4 周时为 8% (6/77)，10 周时为 19% (15/77)。由于毒性而停用两性霉素或氟胞嘧啶的患者在 2 周时的累积比例为 20% (16/77)。此外，院内死亡率与接受 ≤ 10 天的诱导治疗（优势比 = 4.5，95% CI 1.2–17.1，P  = 0.028）或 2 周后脑脊液真菌培养阳性（优势比 = 3.8、95 % CI 1.1–13.5，P  = 0.035）。

结论

在这项“真实世界”研究中，两性霉素加氟胞嘧啶显示 HIV 相关隐球菌脑膜炎患者的早期死亡率较低。由于不良事件而提前停药是中等的。需要更有效和更安全的抗真菌剂来改善隐球菌性脑膜炎的结果。