Induction therapy with high‐dose fluconazole plus flucytosine for human immunodeficiency virus‐uninfected cryptococcal meningitis patients: Feasible or not?

氟胞嘧啶 氟康唑 医学 内科学 脑膜炎 胃肠病学 不利影响 隐球菌病 免疫学 外科 抗真菌 皮肤病科
作者
Hua‐Zhen Zhao,Jiahui Cheng,Ling‐Hong Zhou,Yu Luo,Rong‐Sheng Zhu,Ying‐Kui Jiang,Xuan Wang,Liping Zhu
出处
期刊:Mycoses [Wiley]
卷期号:66 (1): 59-68 被引量:2
标识
DOI:10.1111/myc.13528
摘要

Cryptococcal meningitis (CM) is increasingly recognised in human immunodeficiency virus (HIV)-uninfected patients with high mortality. The efficacy and safety profiles of induction therapy with high-dose fluconazole plus flucytosine remain unclear.HIV-uninfected CM patients who received high-dose fluconazole (800 mg/d) for initial therapy in Huashan Hospital were included in this retrospective study from January 2013 to December 2018. Efficacy and safety of initial therapy, clinical outcomes and risk factors were evaluated.Twenty-seven (71.1%) patients who received high-dose fluconazole with flucytosine combination therapy and 11 (28.9%) having fluconazole alone for induction therapy were included. With a median duration of 42 days (IQR, 28-86), the successful response rate of initial therapy was 76.3% (29/38), while adverse drug reactions occurred in 14 patients (36.8%). The rate of persistently positive cerebrospinal fluid (CSF) culture results was 30.6% at 2 weeks, which was significantly associated with CSF CrAg titre >1:1280 (OR 9.56; 95% CI 1.40-103.65; p = .010) and CSF culture of Cryptococcus >3.9 log10 CFU/ml (OR 19.20; 95% CI 1.60-920.54; p = .011), and decreased to 8.6% at 4 weeks. One-year mortality was 15.8% (6/38), and low serum albumin (35 g/L) was found as an independent risk factor for 1-year mortality (HR 6.31; 95% CI 1.150-34.632; p = .034).Induction therapy with high-dose fluconazole (800 mg/d), combined with flucytosine, effectively treated HIV-uninfected CM and was well tolerated. Long-term fluconazole treatment with continued monitoring is beneficial for patients with persistent infection.

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