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

• Published in: Mycoses 2023-01, Vol.66 (1), p.59-68
• Main Authors: Zhao, Hua‐Zhen, Cheng, Jia‐Hui, Zhou, Ling‐Hong, Luo, Yu, Zhu, Rong‐Sheng, Jiang, Ying‐Kui, Wang, Xuan, Zhu, Li‐Ping
• Format: Article
• Language: English
• Subjects: Antifungal Agents - adverse effects; Cerebrospinal fluid; cryptococcal meningitis; Drug Therapy, Combination; Fluconazole; Fluconazole - adverse effects; Flucytosine; Flucytosine - adverse effects; high dose; HIV; HIV Infections - complications; HIV Infections - drug therapy; HIV‐uninfected; Human immunodeficiency virus; Humans; Immune system; Induction Chemotherapy; Induction therapy; Meningitis; Meningitis, Cryptococcal - complications; Mortality; Original; Patients; Retrospective Studies; Risk factors
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/myc.13528

Background 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. Methods 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. Results 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 log10CFU/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). Conclusions 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.