两性霉素B去氧胆酸盐、两性霉素B脂质体和伏立康唑诱导治疗HIV相关性隐球菌脑膜炎的效果比较

新发传染病电子杂志 ›› 2019, Vol. 4 ›› Issue (2): 97-102.

两性霉素B去氧胆酸盐、两性霉素B脂质体和伏立康唑诱导治疗HIV相关性隐球菌脑膜炎的效果比较

陶然^#1, 师金川^#2, 郭永征¹, 黄凡³, 许利军¹, 陈英¹, 楼方圆¹, 黄莺¹, 徐燕¹, 朱彪¹, 陈耀凯⁴, 喻剑华²

1.浙江大学医学院附属第一医院传染病诊治国家重点实验室,杭州 310003;
2.杭州市西溪医院感染科二科,杭州 3100023;
3.福建省建新医院感染科,福州 350025;
4.重庆市公共卫生临床救治中心,重庆 400036

出版日期:2019-06-30 发布日期:2020-07-21
通讯作者: 许利军, Email：xuli-jun@hotmail.com
作者简介:#：共同第一作者：陶然、师金川

Comparison of amphotericin B deoxycholate, amphotericin B liposome and voriconazole as induction treatment on HIV-related cryptococcal meningitis

TAO Ran¹, SHI Jin-chuan², GUO Yong-zheng¹, XU Li-jun¹, CHEN Ying¹, LOU Fang-yuan¹, HUANG Ying¹, XU Yan¹, ZHU Biao¹, CHEN Yao-kai³, YU Jian-hua²

1. he State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China;
2. Department of infectious diseases, XiXi hospital, Hangzhou 310023, China;
3. Department of infectious diseases, JianXin hospital, Fuzhou 350025, China;
4. Chongqing public health medical center, Chongqing 400036, China

Online:2019-06-30 Published:2020-07-21

摘要/Abstract

摘要： 目的比较两性霉素B去氧胆酸盐（AmB）+5氟胞嘧啶(5FC)±氟康唑（Flu）、两性霉素B脂质体(LipAmB)+5FC和伏立康唑（Vori）+5FC作为诱导方案对于HIV相关隐球菌脑膜炎的治疗效果。方法对2010年1月至2017年12月年接受AmB+5FC±Flu、LipAmB+5FC和Vori+5FC诱导方案的85例HIV相关隐球菌脑膜炎患者进行回顾性分析,比较3组患者间药物副作用以及10周生存率。结果低钾和肌酐升高比例在AmB+5FC±Flu诱导组患者高于Vori+5FC诱导组（P=0.016和P=0.047）,但是在LipAmB+5FC诱导组和Vori+5FC诱导组以及AmB+5FC±Flu诱导组和LipAmB+5FC诱导组的10周累计生存率分别为96.6%,85.5%和76.2%（Log-Rank P=0.093）,组间比较无统计学意义(P=0.079,P=0.089;P=0.365,P=0.724),其中,LipAmB+5FC组10周累计生存率高于Vori+5FC 组(Log-Rank P=0.022)。结论 Vori+5FC诱导治疗方案效果不优于AmB+5FC±Flu或LipAmB+5FC的治疗方案,但是副作用较少;LipAmB+5FC的诱导治疗不劣于AmB+5FC±Flu治疗方案。

关键词: 艾滋病, 隐球菌脑膜炎, 两性霉素B去氧胆酸盐, 两性霉素B脂质体, 伏立康唑

Abstract: Objective To compare clinical effects between amphotericin B deoxycholate (AmB) + 5 fluorocytosine (5FC) ± fluconazole (Flu), amphotericin B liposome (LipAmB) + 5FC and voriconazole (Vori) + 5FC as induction treatment on HIV-related cryptococcal meningitis.Methods A retrospective cohort study was performed to compare the side effects and 10-week cumulative survival rates in 85 HIV- related cryptococcal meningitis patients who treated with AmB + 5FC ± Flu, LipAmB + 5FC or Vori + 5FC as induction regimens from 2010 to 2017.Result sThe incidences of hypokalemia and creatinine elevation were higher in the AmB + 5FC ± Flu group than in Vori + 5FC group (P=0.016, P=0.047, respectively), but no statistical significance was found in LipAmB + 5FC group vs. Vori + 5FC group, and AmB + 5FC ± Flu vs. LipAmB+5FC group. The 10-week cumulative survival rate of patients was 96.6%, 85.5%, and 76.2% in LipAmB + 5FC group, AmB + 5FC ± Flu group and Vori + 5FC, respectively (Log-Rank P=0.093), and the 10-week cumulative survival rate of patients in LipAmB + 5FC group was higher than those in Vori + 5FC group (Log-Rank P=0.022).Conclusion The Vori + 5FC as induction therapy is not superior to the AmB + 5FC ± Flu or LipAmB + 5FC regimen, but related with less side effects. LipAmB + 5FC as induction therapy is not inferior to the AmB + 5FC ± Flu regimen.

Key words: AIDS, Cryptococcal meningitis, Amphotericin B deoxycholate, Amphotericin B liposome, Voriconazole

陶然, 师金川, 郭永征, 黄凡, 许利军, 陈英, 楼方圆, 黄莺, 徐燕, 朱彪, 陈耀凯, 喻剑华. 两性霉素B去氧胆酸盐、两性霉素B脂质体和伏立康唑诱导治疗HIV相关性隐球菌脑膜炎的效果比较[J]. 新发传染病电子杂志, 2019, 4(2): 97-102.

TAO Ran, SHI Jin-chuan, GUO Yong-zheng, XU Li-jun, CHEN Ying, LOU Fang-yuan, HUANG Ying, XU Yan, ZHU Biao, CHEN Yao-kai, YU Jian-hua. Comparison of amphotericin B deoxycholate, amphotericin B liposome and voriconazole as induction treatment on HIV-related cryptococcal meningitis[J]. Electronic Journal of Emerging Infectious Diseases, 2019, 4(2): 97-102.

参考文献

[1] Williamson PR, Jarvis JN, Panackal AA, et al.Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy[J]. Nat Rev Neurol, 2017, 13(1): 13-24.
[2] Rajasingham R, Smith RM, Park BJ, et al.Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis[J]. Lancet Infect Dis, 2017, 17(8): 873-881.
[3] Perfect JR, Dismukes WE, Dromer F, et al.Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america[J]. Clin Infect Dis, 2010, 50(3): 291-322.
[4] Liu ZY, Wang GQ, Zhu LP, et al.Expert consensus on the diagnosis and treatment of cryptococcal meningitis[J]. Zhonghua Nei Ke Za Zhi, 2018, 57(5): 317-323.
[5] Bicanic T, Wood R, Meintjes G, et al.High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial[J]. Clin Infect Dis, 2008, 47(1): 123-130.
[6] Livermore J, Howard SJ, Sharp AD, et al.Efficacy of an Abbreviated Induction Regimen of Amphotericin B Deoxycholate for Cryptococcal Meningoencephalitis: 3 Days of Therapy Is Equivalent to 14 Days[J]. mBio, 2014, 5(1): e00725-00713.
[7] Li SS, Tang XY, Zhang SG, et al.Voriconazole combined with low-dose amphotericin B liposome for treatment of cryptococcal meningitis[J]. Infect Dis (Lond), 2016, 48(7): 563-565.
[8] Gamaletsou MN, Sipsas NV, Kontoyiannis DP, et al.Successful salvage therapy of refractory HIV-related cryptococcal meningitis with the combination of liposomal amphotericin B, voriconazole, and recombinant interferon-gamma[J]. Diagn Microbiol Infect Dis, 2012, 74(4): 409-411.
[9] Yao Y, Zhang JT, Yan B, et al.Voriconazole: a novel treatment option for cryptococcal meningitis[J]. Infect Dis (Lond), 2015, 47(10): 694-700.
[10] Xu L, Zhang X, Guo Y, et al.Unique clinical features of cryptococcal meningitis among Chinese patients without predisposing diseases against patients with predisposing diseases[J]. Med Mycol, 2019, 51(2): 113-121.
[11] Fang W, Fa Z, Liao W.Epidemiology of Cryptococcus and cryptococcosis in China[J]. Fungal Genet Biol, 2015, 78: 7-15.
[12] Liao CH, Chi CY, Wang YJ, et al.Different presentations and outcomes between HIV-infected and HIV-uninfected patients with Cryptococcal meningitis[J]. J Microbiol Immunol Infect, 2012, 45(4): 296-304.
[13] Liu Y, Kang M, Wu SY, et al.Different characteristics of cryptococcal meningitis between HIV-infected and HIV-uninfected patients in the Southwest of China[J]. Med Mycol, 2017, 55(3): 255-261.
[14] Molloy SF, Kanyama C, Heyderman RS, et al.Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa[J]. N Engl J Med, 2018, 378(11): 1004-1017.
[15] Lee YC, Wang JT, Sun HY, et al.Comparisons of clinical features and mortality of cryptococcal meningitis between patients with and without human immunodeficiency virus infection[J]. J Microbiol Immunol Infect, 2011, 44(5): 338-345.
[16] Corral MJ, Serrano DR, Moreno I, et al.Efficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis[J]. J Antimicrob Chemother, 2014, 69(12): 3268-3274.
[17] Yasu T, Konuma T, Oiwa-Monna M, et al.Efficacy and Safety of Low-Dose Liposomal Amphotericin B in Adult Patients Undergoing Unrelated Cord Blood Transplantation[J]. Antimicrob Agents Chemother, 2018, 62(11): e01205-e01218.
[18] Subira M, Martino R, Gomez L, et al.Low-dose amphotericin B lipid complex vs. conventional amphotericin B for empirical antifungal therapy of neutropenic fever in patients with hematologic malignancies--a randomized, controlled trial[J]. Eur J Haematol, 2004, 72(5): 342-347.