结核性脑膜炎的诊断和治疗

结核性脑膜炎(TBM)是一种严重的肺外结核性,约占全部结核病的1%。TBM的死亡率和致残率高,至今仍是发展中国家最严重的疾病之一。儿童患者及合并HIV感染的结核性脑膜炎患者死亡率明显增高。结核性脑膜炎的具体发病机制仍不清楚,细菌和宿主的遗传因素在结脑的发病机制中发挥了至关重要的作用。尽管现代医学技术的进展,TBM的早期诊断仍存在困难。TBM的诊断依赖于临床表现、实验室检查以及影像学检查,脑脊液细菌涂片或培养找到结核分枝杆菌可确诊。早期诊断和治疗尤为关键。临床上往往从经验判断开始抗结核治疗。WHO指南推荐至少六个月的抗结核治疗。然而,部分指南推荐延长抗结核治疗至9-12个月。早期使用类固醇类激素可降低死亡率。抗结核药物耐药性与高死亡率相关。该综述描述了结脑的各个方面,重点强调结核性脑膜炎的早期诊断和治疗。     

Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis

Background

Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.

Methods and Findings:

We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800–1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to $467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to $44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of $15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.

Conclusions

Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is “very cost effective” per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease. Please see later in the article for the Editors'' Summary.     

Treatment of Gram-Negative Bacillary Meningitis With Intrathecal Gentamicin

In order to evaluate the effect of intrathecal gentamicin on gram-negative bacillary meningitis, twenty-eight patients were treated with intralumbar or intraventricular gentamicin in combination with systemic gentamicin and with other antibiotics. Sterile cerebrospinal fluid was achieved in 21/22 (95%) episodes of documented gram-negative bacillary meningitis in patients who received more than one day of therapy. Seventy-seven percent of these patients survived their infection. The mean cerebrospinal fluid gentamicin level measured 24 hours after intrathecal administration was 5.9 ug/ml following intralumbar administration and 11.1 ug/ml following intraventricular administration. Toxic side effects due to intrathecal administration of gentamicin were not noted. These findings suggest that both intralumbar and intraventricular administration of gentamicin are safe and efficacious in the treatment of gram-negative bacillary meningitis.