Abstract：
OBJECTIVE: The objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis.
METHODS: We quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5).
RESULTS: Bacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51-68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 104 DNA copies/mL (IQR 3.4 × 103-1.2 × 105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9-105.6), and was moderately correlated with CSF bacterial loads (Spearman\'s rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0-2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6-2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4-3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6-3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6-3.9; p < 0.001).
CONCLUSIONS: High CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis.
METHODS: We quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5).
RESULTS: Bacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51-68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 104 DNA copies/mL (IQR 3.4 × 103-1.2 × 105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9-105.6), and was moderately correlated with CSF bacterial loads (Spearman\'s rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0-2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6-2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4-3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6-3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6-3.9; p < 0.001).
CONCLUSIONS: High CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis.
摘要：
目的：本研究的目的是确定成人肺炎球菌性脑膜炎患者脑脊液（CSF）细菌负荷的作用。
方法：我们量化了成人社区获得性肺炎球菌性脑膜炎诊断腰椎穿刺的CSF样本中的细菌负荷。我们还测量了补体5a（C5a）的CSF浓度，并确定细菌负荷之间的关联，临床特征,C5a和不利的结果（格拉斯哥结果量表评分<5）。
结果：对152份CSF样品中的细菌负荷进行了定量。这些患者的中位年龄为61岁（四分位间距[IQR]51-68），152人中有69人(45%)是女性。CSF细菌载量中位数为1.6x104DNA拷贝/ml（IQR3.4x103-1.2x105），并且与CSF白细胞计数或CSF蛋白浓度无关。脑脊液C5a浓度中位数为35.8mg/L（IQR15.9-105.6），与脑脊液细菌负荷中度相关(Spearman’srho=0.42；p<0001)。高细菌负荷与并发症的发生有关，如循环性休克(比值比/对数增加[OR]2.4,95CI2.0-2.9;p<0.001)和脑血管并发症[OR1.9,95CI1.6-2.3;p<0.001])。高细菌负荷也与不良结局(OR2.8,95CI2.4-3.3;p<0.001)和死亡(OR3.1,95CI2.6-3.8;p<0.001)相关。在包括年龄的多变量回归模型中，免疫受损状态，脑膜外感染焦点，入院格拉斯哥昏迷量表评分和脑脊液C5a浓度，CSF细菌负荷仍然是不良结局的独立预测因子（校正OR2.5，95CI1.6-3.9；p<0.001）。
结论：高CSF细菌负荷可预测成人肺炎球菌性脑膜炎的并发症和不利结局的发展。
方法：我们量化了成人社区获得性肺炎球菌性脑膜炎诊断腰椎穿刺的CSF样本中的细菌负荷。我们还测量了补体5a（C5a）的CSF浓度，并确定细菌负荷之间的关联，临床特征,C5a和不利的结果（格拉斯哥结果量表评分<5）。
结果：对152份CSF样品中的细菌负荷进行了定量。这些患者的中位年龄为61岁（四分位间距[IQR]51-68），152人中有69人(45%)是女性。CSF细菌载量中位数为1.6x104DNA拷贝/ml（IQR3.4x103-1.2x105），并且与CSF白细胞计数或CSF蛋白浓度无关。脑脊液C5a浓度中位数为35.8mg/L（IQR15.9-105.6），与脑脊液细菌负荷中度相关(Spearman’srho=0.42；p<0001)。高细菌负荷与并发症的发生有关，如循环性休克(比值比/对数增加[OR]2.4,95CI2.0-2.9;p<0.001)和脑血管并发症[OR1.9,95CI1.6-2.3;p<0.001])。高细菌负荷也与不良结局(OR2.8,95CI2.4-3.3;p<0.001)和死亡(OR3.1,95CI2.6-3.8;p<0.001)相关。在包括年龄的多变量回归模型中，免疫受损状态，脑膜外感染焦点，入院格拉斯哥昏迷量表评分和脑脊液C5a浓度，CSF细菌负荷仍然是不良结局的独立预测因子（校正OR2.5，95CI1.6-3.9；p<0.001）。
结论：高CSF细菌负荷可预测成人肺炎球菌性脑膜炎的并发症和不利结局的发展。
