细菌性脑膜炎动物模型的脑脊液早期细菌动力学变化

目的 建立细菌性脑膜炎动物模型,了解细菌感染后48 h内脑脊液(CSF)细菌载量变化规律,为疾病的诊疗及预后判断提供参考依据.方法 以新西兰大白兔作为研究对象,通过小脑延髓池穿刺建立细菌性脑膜炎动物模型,观察不同菌量的大肠埃希菌和金黄色葡萄球菌(金葡菌)建立模型时动物的死亡情况.明确CSF感染菌量与动物死亡率间的对应关系.选择合适的接种菌量,进行脑膜炎CSF细菌载量观察实验.将实验动物分为4组(每组12只):大肠埃希菌脑膜炎模型组,大肠埃希菌脑膜炎+头孢曲松治疗组、金葡菌脑膜炎模型组、金葡菌脑膜炎+万古霉素治疗组,在建立模型后0、12、24、36和48 h分别进行CSF细菌定量培养、CSF及外周血WBC计数,进而分析细菌性脑膜炎CSF细菌载量的变化规律,及其与动物早期死亡率、抗菌药物治疗、CSF的WBC计数间的关系.CSF细菌载量、WBC计数曲线的显著性检验采用协方差分析,相关性检验采用偏相关分析.结果 CSF感染菌量与动物死亡率间呈现S型曲线关系,CSF细菌载量在蛛网膜下腔接种细菌12～24 h达到高峰,而后逐步下降,有效的抗菌药物治疗可显著加快下降过程,大肠埃希菌脑膜炎模型组与大肠埃希菌脑膜炎+头孢曲松治疗组相比(F=27.10,P<0.01),金葡菌脑膜炎模型组与金葡菌脑膜炎+万古霉素治疗组相比(F＝5.97,P=0.016),差异均有统计学意义.大肠埃希菌脑膜炎模型组和金葡菌脑膜炎模型组中的CSF的WBC计数与CSF细菌载量之间存在正相关性(r＝0.89、0.84;P=0.046、0.049).结论 在细菌性脑膜炎的治疗中,应早期,足量地使用有效抗生素,以控制CSF细菌载量,降低死亡率.CSF的WBC计数可作为反映CSF细菌载量的指标,指导临床治疗.

The early dynamics study of cerebrospinal fluid bacterial in a rabbit model of bacterial meningitis

Objective To study the dynamics changes of cerebrospinal fluid (CSF) bacterial load within 48 h after infection in a rabbit meningitis model, and provide information for diagnosis,treatment and prognosis of this disease. Methods Taking New Zealand white rabbit as the study object, meningitis model was established via cerebellar cistern puncture with different concentrations of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) to explore the relationship between the mortality of animals and the subarachnoid inoculation dosage. The dynamics study of CSF bacterial load was conducted with proper inoculation bacterial dosage. Forty-eight rabbits were separated into four groups (12 each group): E. coli meningitis model group, E. coli meningitis + ceftriaxone treated group, S. aureus meningitis model group and S. aureus meningitis + vancomycin treated group. At 0,12, 24, 36 and 48 h of inoculation, CSF and blood samples were obtained for CSF bacterial quantitative culture, CSF leukocyte count and peripheral blood leukocyte count. Finally, the relationships between the early mortality of animals, the efficacy of antibiotics, CSF leukocyte counts and the dynamics changes of CSF bacterial load were analyzed in the bacterial meningitis rabbit model.The CSF bacterial load and the white blood cell count curve were compared by analysis of covariance (ANOVA). Correlation test was done using correlate partial analysis. Results The relationship between subarachnoid inoculation dosage and the mortality of rabbits presented S-curve correlation.The bacterial load in subarachnoid space peaked in 12-24 h after infection and then gradually decreased. Effective antibiotic therapy could significantly speed up the decline of this process. There were significantly different between E. coli meningitis model group and E. coli meningitis+ceftriaxone treated group (F= 27. 10, P<0. 01), between S. aureus meningitis model group and S. aureus meningitis + vancomycin treated group (F=5. 97, P = 0. 016). There was a positive correlation between CSF bacterial load and CSF leukocyte count in E. coli and S. aureus meningitis model groups (r=0. 89, 0.84, respectively; P = 0.046, 0.049, respectively). Conclusions In the treatment of bacterial meningitis, effective and sufficient antibiotics should be used as soon as possible to control the CSF bacterial load and reduce the mortality. The CSF leukocyte count can be used as indicator of CSF bacterial load and guide the antibiotic treatment in clinical bacterial meningitis.