501例HIV相关隐球菌性脑膜炎患者联合队列中的死亡决定因素：对改善预后的启示
Determinants of mortality in a combined cohort of 501 patients with HIV-associated Cryptococcal meningitis: implications for improving outcomes.
作者信息
Jarvis Joseph N, Bicanic Tihana, Loyse Angela, Namarika Daniel, Jackson Arthur, Nussbaum Jesse C, Longley Nicky, Muzoora Conrad, Phulusa Jacob, Taseera Kabanda, Kanyembe Creto, Wilson Douglas, Hosseinipour Mina C, Brouwer Annemarie E, Limmathurotsakul Direk, White Nicholas, van der Horst Charles, Wood Robin, Meintjes Graeme, Bradley John, Jaffar Shabbar, Harrison Thomas
机构信息
Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, United Kingdom.
出版信息
Clin Infect Dis. 2014 Mar;58(5):736-45. doi: 10.1093/cid/cit794. Epub 2013 Dec 6.
BACKGROUND
Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes.
METHODS
Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality.
RESULTS
Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0-1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4-11.1), high peripheral white blood cell count (>10 × 10(9) cells/L; OR, 8.7; 95% CI, 2.5-30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART).
CONCLUSIONS
CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes.
背景
隐球菌性脑膜炎（CM）是人类免疫缺陷病毒（HIV）感染者死亡的主要原因。确定与死亡率相关的因素有助于制定改善预后的策略。
方法
在泰国、乌干达、马拉维和南非进行的试验中，对501例HIV相关CM患者进行了为期10周的前瞻性随访。南非患者（n = 266）随访1年。所有研究地点均采用相似的纳入/排除标准。逻辑回归确定了与死亡率独立相关的基线变量。
结果
2周时死亡率为17%，10周时为34%。精神状态改变（比值比[OR]，3.1；95%置信区间[CI]，1.7 - 5.9）、高脑脊液（CSF）真菌负荷（每增加log10菌落形成单位/mL，OR为1.4；95% CI，1.0 - 1.8）、年龄较大（>50岁；OR，3.9；95% CI，1.4 - 11.1）、外周血白细胞计数高（>10×10⁹细胞/L；OR，8.7；95% CI，2.5 - 30.2）、基于氟康唑的诱导治疗以及CSF感染清除缓慢与2周死亡率独立相关。除精神状态改变、真菌负荷高、外周血白细胞计数高和年龄较大外，低体重、贫血（血红蛋白<7.5 g/dL）和低CSF初压与10周时的死亡率独立相关。在随访1年的患者中，总死亡率为41%。13%的患者发生了免疫重建炎症综合征，其与2周时的CSF真菌负荷相关（P = 0.007），但与开始抗逆转录病毒治疗（ART）的时间无关。
结论
CSF真菌负荷、精神状态改变和感染清除率可预测HIV相关CM的急性死亡率。结果表明，早期诊断、基于两性霉素的更快速杀菌方案以及通过ART迅速实现免疫重建是改善预后的重点。
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