Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality.
Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality.
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DOI：
10.3390/jof9010046
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发表时间：
2022-12-28
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影响因子：
--
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中科院分区：
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隐球菌是撒哈拉以南非洲与艾滋病有关的脑膜炎的主要原因。在使用CSF隐球菌抗原（CrAg）诊断为隐球菌脑膜炎的个体中，无菌脑脊液（CSF）培养的临床意义尚不清楚。我们前瞻性招募了765名艾滋病毒阳性乌干达人，他们在2010年11月至2017年5月期间首次发作隐球菌脑膜炎。所有患者均接受基于阿替西他滨的诱导治疗。我们根据基线CSF定量隐球菌培养负荷的三分位数对参与者进行分组，并比较临床特征、CSF免疫特征和18周死亡率。我们发现55（7%）CSF CrAg阳性的参与者与无菌CSF文化。与非无菌组相比，无菌CSF培养物的参与者具有更高的CD 4计数，更低的CSF开放压力，并且更频繁地接受ART。到18周时，无菌培养物组中47% [26/55]死亡，而低培养三分位数中35% [83/235]，中三分位数中46% [107/234]，高三分位组为56% [135/241]（P < 0.001）。不育组的CSF干扰素-γ（IFN-γ）、IFN-α、白细胞介素（IL）-6、IL-17、G-CSF、GM-CSF和趋化因子CXCL 2水平高于非不育组。尽管具有无菌CSF培养物的人具有更高的CD 4计数、更低的CSF开放压力和与更好的隐球菌控制相关的CSF细胞因子谱（例如，IFN-γ占优势），死亡率与真菌负荷较高的患者相似。这一意想不到的发现挑战了CSF真菌负荷增加与死亡率增加相关的传统范式，但与损伤-反应框架模型一致。
Cryptococcus is the leading cause of AIDS-related meningitis in sub-Saharan Africa. The clinical implications of a sterile cerebrospinal fluid (CSF) culture among individuals diagnosed with cryptococcal meningitis using CSF cryptococcal antigen (CrAg) are unclear. We prospectively enrolled 765 HIV-positive Ugandans with first-episode cryptococcal meningitis from November 2010 to May 2017. All persons were treated with amphotericin-based induction therapy. We grouped participants by tertile of baseline CSF quantitative Cryptococcus culture burden and compared clinical characteristics, CSF immune profiles, and 18-week mortality. We found 55 (7%) CSF CrAg-positive participants with sterile CSF cultures. Compared to the non-sterile groups, participants with sterile CSF cultures had higher CD4 counts, lower CSF opening pressures, and were more frequently receiving ART. By 18 weeks, 47% [26/55] died in the sterile culture group versus 35% [83/235] in the low culture tertile, 46% [107/234] in the middle tertile, and 56% [135/241] in the high tertile (p < 0.001). The sterile group had higher levels of CSF interferon-gamma (IFN-γ), IFN-α, interleukin (IL)-6, IL-17, G-CSF, GM-CSF, and chemokine CXCL2 compared with non-sterile groups. Despite persons with sterile CSF cultures having higher CD4 counts, lower CSF opening pressures, and CSF cytokine profiles associated with better Cryptococcus control (e.g., IFN-γ predominant), mortality was similar to those with higher fungal burdens. This unexpected finding challenges the traditional paradigm that increasing CSF fungal burdens are associated with increased mortality but is consistent with a damage-response framework model.
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DOI：
10.1016/s1473-3099(10)70170-5
发表时间：
2010-11
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Haddow LJ;Colebunders R;Meintjes G;Lawn SD;Elliott JH;Manabe YC;Bohjanen PR;Sungkanuparph S;Easterbrook PJ;French MA;Boulware DR;International Network for the Study of HIV-associated IRIS (INSHI)
通讯作者：
International Network for the Study of HIV-associated IRIS (INSHI)
影响因子：
--
作者：
Pirofski LA;Casadevall A
通讯作者：
Casadevall A
影响因子：
6.4
作者：
Gerstein, Aleeza C.;Jackson, Katrina M.;Nielsen, Kirsten
通讯作者：
Nielsen, Kirsten
影响因子：
6.4
作者：
Boulware, David R.;Bonham, Shulamith C.;Bohjanen, Paul R.
通讯作者：
Bohjanen, Paul R.
在撒哈拉以南非洲的抗逆转录病毒治疗和经验丰富的患者中，与HIV相关的隐球菌脑膜炎的短期死亡率结果。
影响因子：
4.2
作者：
Kalata N;Ellis J;Kanyama C;Kuoanfank C;Temfack E;Mfinanga S;Lesikari S;Chanda D;Lakhi S;Nyazika T;Chan AK;van Oosterhout JJ;Chen T;Hosseinipour MC;Lortholary O;Wang D;Jaffar S;Loyse A;Heyderman RS;Harrison TS;Molloy SF
通讯作者：
Molloy SF