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一项在泰国开展的关于采用高剂量两性霉素B治疗艾滋病相关隐球菌性脑膜炎的前瞻性研究。

A prospective study of AIDS-associated cryptococcal meningitis in Thailand treated with high-dose amphotericin B.

作者信息

Pitisuttithum P, Tansuphasawadikul S, Simpson A J, Howe P A, White N J

机构信息

Clinical Infectious Diseases Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

出版信息

J Infect. 2001 Nov;43(4):226-33. doi: 10.1053/jinf.2001.0916.

DOI:10.1053/jinf.2001.0916
PMID:11869059
Abstract

OBJECTIVE

To assess kinetic of cryptococci in the cerebrospinal fluid (CSF) and outcome of AIDS-associated cyptococcal meningitis after high-dose amphotericin B.

PATIENTS AND METHODS

A prospective study involving Thai adults (n=106) with cryptococcal meningitis associated with AIDS was conducted to determine the kinetic of cryptococci in CSF and prognostic factors affecting survival after high-dose amphotericin B (0.7 mg/kg/day) followed by oral azole treatment. Cerebrospinal fluids were collected for cryptococcal count and culture at weekly intervals for at least 2 weeks or until CSF cultures were negative for cryptococci. All patients were followed monthly for 1 year or until death in order to detect relapse or occurrence of any other opportunistic infection.

RESULTS

A total of 106 AIDS patients with cryptococcal meningitis were enrolled. The geometric mean (range) total and viable cryptococcal counts in CSF on admission were 430,000 (1000 to 3.4 x 10(7)) and 31,000 (10 to 1.4 x 10(7)) per ml, respectively. Both total and viable cryptococcal counts declined monoexponentially with an elimination half life of 4 days. The cumulative CSF yeast clearance rates were 38% and 56% at 2 and 4 weeks, respectively. Early death was associated significantly with previous history of weight loss [relative risk (RR)=2.2; 95% CI, 1.2-3.9], Glasgow Coma Score <13 (RR=2.33; 95% CI, 1.55-3.50), and hypoalbuminaemia (P<0.001). Later mortality was associated delayed CSF yeast clearance (RR=3.6; 95% CI, 1.9--6.4) and relapse (RR=3.9; 95% CI, 1.4-10.8).

CONCLUSION

High-dose amphotericin B was not as effective as previously thought. Cumulative mortality at 2 weeks, 4 weeks and 1 year were 16%, 24% and 76%, respectively.

摘要

目的

评估高剂量两性霉素B治疗后艾滋病相关隐球菌性脑膜炎患者脑脊液中隐球菌的动态变化及预后。

患者与方法

对106例泰国成年艾滋病相关隐球菌性脑膜炎患者进行前瞻性研究,以确定脑脊液中隐球菌的动态变化以及影响高剂量两性霉素B(0.7mg/kg/天)联合口服唑类药物治疗后生存的预后因素。每周采集脑脊液进行隐球菌计数和培养,至少持续2周或直至脑脊液培养隐球菌阴性。所有患者每月随访1年或直至死亡,以检测复发或任何其他机会性感染的发生情况。

结果

共纳入106例艾滋病相关隐球菌性脑膜炎患者。入院时脑脊液中隐球菌总数和活菌数的几何平均数(范围)分别为每毫升43万(1000至3.4×10⁷)和3.1万(10至1.4×10⁷)。隐球菌总数和活菌数均呈单指数下降,消除半衰期为4天。2周和4周时脑脊液酵母菌清除率分别为38%和56%。早期死亡与既往体重减轻史显著相关[相对危险度(RR)=2.2;95%可信区间(CI),1.2 - 3.9]、格拉斯哥昏迷评分<13(RR = 2.33;95%CI,1.55 - 3.50)和低白蛋白血症(P<0.001)。晚期死亡与脑脊液酵母菌清除延迟(RR = 3.6;95%CI,1.9 - 6.4)和复发(RR = 3.9;95%CI,1.4 - 10.8)相关。

结论

高剂量两性霉素B的效果不如先前认为的那样好。2周、4周和1年时的累积死亡率分别为16%、24%和76%。

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