Abstract：
BACKGROUND: Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day.
METHODS: We analyzed data from three clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (N = 94) or amphotericin B deoxycholate at 0.7-1.0 mg/kg/day with flucytosine (N = 404) as induction therapy. We compared participant baseline characteristics, CSF early fungicidal activity (EFA), and 10-week mortality.
RESULTS: We included 498 participants in this analysis, of whom 201 had available EFA data (N = 46 liposomal amphotericin; N = 155 amphotericin deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA = 0.495 log10 CFU/mL/day; 95%CI, 0.355-0.634) differ from amphotericin B deoxycholate (mean EFA = 0.402 log10 CFU/mL; 95%CI, 0.360-0.445) (P = 0.13). Mortality at 10 weeks trended lower for liposomal amphotericin (28.2%) vs amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted Hazard Ratio = 0.74; 95%CI, 0.44-1.25; P = 0.26).
CONCLUSIONS: Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis.
METHODS: We analyzed data from three clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (N = 94) or amphotericin B deoxycholate at 0.7-1.0 mg/kg/day with flucytosine (N = 404) as induction therapy. We compared participant baseline characteristics, CSF early fungicidal activity (EFA), and 10-week mortality.
RESULTS: We included 498 participants in this analysis, of whom 201 had available EFA data (N = 46 liposomal amphotericin; N = 155 amphotericin deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA = 0.495 log10 CFU/mL/day; 95%CI, 0.355-0.634) differ from amphotericin B deoxycholate (mean EFA = 0.402 log10 CFU/mL; 95%CI, 0.360-0.445) (P = 0.13). Mortality at 10 weeks trended lower for liposomal amphotericin (28.2%) vs amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted Hazard Ratio = 0.74; 95%CI, 0.44-1.25; P = 0.26).
CONCLUSIONS: Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis.
摘要：
背景：关于每日脂质体两性霉素B联合氟胞嘧啶诱导方案治疗隐球菌性脑膜炎的抗真菌活性的数据有限，在高收入国家推荐。在其注册临床试验中，与两性霉素B脱氧胆酸盐相比，以前3mg/kg的脂质体两性霉素B单药治疗未能达到非劣效性标准。我们旨在比较接受辅助氟胞嘧啶100mg/kg/天的HIV相关隐球菌性脑膜炎患者中每日两性霉素B脱氧胆酸盐和每日脂质体两性霉素之间的定量抗真菌活性和死亡率。
方法：我们分析了三项涉及HIV相关隐球菌性脑膜炎患者的临床研究的数据，这些患者每天接受3mg/kg/天的脂质体两性霉素B和氟胞嘧啶（N=94）或0.7-1.0mg/kg/天的两性霉素B脱氧胆酸盐和氟胞嘧啶（N=404）作为诱导治疗。我们比较了参与者的基线特征，CSF早期杀菌活性（EFA），和10周死亡率。
结果：我们在这项分析中纳入了498名参与者，其中201人具有可用的EFA数据(N=46脂质体两性霉素;N=155两性霉素脱氧胆酸盐).总的来说,没有统计学证据表明脂质体两性霉素B的抗真菌活性(平均EFA=0.495log10CFU/mL/天;95CI,0.355~0.634)与两性霉素B脱氧胆酸盐(平均EFA=0.402log10CFU/mL;95CI,0.360~0.445)(P=0.13)不同.在10周时,脂质体两性霉素(28.2%)与两性霉素B脱氧胆酸盐(34.6%)的死亡率有降低趋势,但在调整基线特征时没有统计学差异(调整后的危险比=0.74;95CI,0.44-1.25;P=0.26)。
结论：每日脂质体两性霉素B诱导显示，与两性霉素B脱氧胆酸盐联合氟胞嘧啶治疗HIV相关性隐球菌性脑膜炎时，脑脊液真菌清除率和10周死亡率相似。
方法：我们分析了三项涉及HIV相关隐球菌性脑膜炎患者的临床研究的数据，这些患者每天接受3mg/kg/天的脂质体两性霉素B和氟胞嘧啶（N=94）或0.7-1.0mg/kg/天的两性霉素B脱氧胆酸盐和氟胞嘧啶（N=404）作为诱导治疗。我们比较了参与者的基线特征，CSF早期杀菌活性（EFA），和10周死亡率。
结果：我们在这项分析中纳入了498名参与者，其中201人具有可用的EFA数据(N=46脂质体两性霉素;N=155两性霉素脱氧胆酸盐).总的来说,没有统计学证据表明脂质体两性霉素B的抗真菌活性(平均EFA=0.495log10CFU/mL/天;95CI,0.355~0.634)与两性霉素B脱氧胆酸盐(平均EFA=0.402log10CFU/mL;95CI,0.360~0.445)(P=0.13)不同.在10周时,脂质体两性霉素(28.2%)与两性霉素B脱氧胆酸盐(34.6%)的死亡率有降低趋势,但在调整基线特征时没有统计学差异(调整后的危险比=0.74;95CI,0.44-1.25;P=0.26)。
结论：每日脂质体两性霉素B诱导显示，与两性霉素B脱氧胆酸盐联合氟胞嘧啶治疗HIV相关性隐球菌性脑膜炎时，脑脊液真菌清除率和10周死亡率相似。
