116例细菌性脑膜炎儿童脑脊液病原菌分布及耐药性分析

目的：了解小儿细菌性脑膜炎病原菌分布特点及其耐药状况,为临床进行及时有效治疗提供依据。方法：回顾分析2008年1月至2012年6月昆明市儿童医院5097例小儿脑脊液中的病原菌分离培养结果及其药敏试验情况。采用K-B纸片法对病原菌进行常用抗生素的敏感性检测并进行分析。结果：5年来共从5097例脑脊液标本中检出病原菌116株,其中革兰阳性菌77株（66.4％）,革兰阴性菌30株（25.9％）,真菌9株（7.8％）,阳性率为2.28%（116/5097）。排名前6 位的病原菌依次为表皮葡萄球菌32株(27.6%),肺炎链球菌15株(12.9%),大肠埃希菌15株(12.9%),溶血葡萄球菌9株(7.8%),新型隐球菌8株(6.9%),金黄色葡萄球菌6株(5.2%)。新生儿及婴儿早期的病原菌主要是凝固酶阴性葡萄球菌,其对青霉素、红霉素、克林霉素敏感率均低于40%;肺炎链球菌对青霉素敏感率仅为13.4%,而对红霉素和克林霉素敏感率达到60.0%;但未见万古霉素耐药的葡萄球菌和肺炎链球菌。革兰阴性杆菌对亚胺培南、美洛培南、头孢哌酮/舒巴坦及头孢吡肟敏感率较高。结论：近5年来小儿细菌性脑膜炎患者病原菌以革兰阳性球菌为主,检出病原菌对常用抗生素耐药性较高;另外,新型隐球菌检出占有一定的比例,应高度注意新型隐球菌性脑膜炎,防止误诊和漏诊。     

Expression of neurotrophic factors in cerebrospinal fluid and plasma of children with viral and bacterial meningoencephalitis

Aim: To evaluate the expression of neurotrophic factors (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF)) and their association with the clinical-radiological characteristics and outcome of children with viral and bacterial meningoencephalitis (ME). Methods: Prospective observational clinical study performed on 13 children with ME and 12 controls with non-inflammatory obstructive hydrocephalus. Neurotrophic factor levels in the cerebro-spinal fluid (CSF) and plasma were measured using an immunoenzymatic assay. Results: High levels of NGF and BDNF were demonstrated in all patients, while GDNF levels did not undergo significant variations. NGF expression in the CSF was higher in viral ME than in bacterial ME and was correlated with CSF cellularity (particularly mononuclear cells). BDNF expression in the CSF was higher in bacterial ME than in viral ME and was correlated with CSF cellularity and blood platelet count. No relationships were noted between CSF protein or serum C-reactive protein levels and the expression of neurotrophic factors. Regarding clinical and radiological features, elevated NGF/BDNF levels in the CSF correlated with higher incidence of seizures and prolonged comatose state and with specific radiological lesions. No correlation was found between NGF/BDNF levels and final outcome.

Conclusions: The variations in neurotrophic factor levels may reflect an endogenous attempt at neuroprotection against biochemical and molecular changes during both viral and bacterial ME. The expression of these factors is likely to play a neuro-immunomodulatory or neurosurvival role in ME infections.     

Differentiating acute bacterial meningitis from acute viral meningitis among children with cerebrospinal fluid pleocytosis: a multivariable regression model

BACKGROUND: Although accurate models for predicting acute bacterial meningitis exist, most have narrow application because of the specific variables selected for them. In this study, we estimate the accuracy of a simple new model with potentially broader applicability. METHODS: On the basis of previous reports, we created a reduced multivariable logistic regression model for predicting bacterial meningitis that relies on age (years) (AGE), cerebrospinal fluid (CSF), total protein (TP) and total neutrophil count (TNC) alone. Data were from children ages 1 month-18 years diagnosed with acute enteroviral or bacterial meningitis whose initial CSF revealed >7 white blood cells/mm. A fractional polynomial model was specified and validated internally by the bootstrap procedure. The area under the receiver operating characteristic curve (discrimination: criterion standard, >0.7), the Hosmer-Lemeshow deciles-of-risk statistic (calibration: criterion standard, P > 0.05) and sensitivity-specificity pairs at prespecified probability thresholds of the model were computed. RESULTS: We identified 60 children with bacterial meningitis and 82 with enteroviral meningitis. At an area under the receiver operating characteristic curve of 0.97, our model represented by the equation: log odds of bacterial meningitis = 0.343 - 0.003 TNC - 34.802 TP + 21.991 TP - 0.345 AGE, was highly accurate when differentiating between bacterial and enteroviral meningitis. The model fit the data well (Hosmer-Lemeshow statistic; P =[r] 0.53). At probability cutoffs between 0.1 and 0.4, the model had sensitivity values between 98 and 92% and specificity values between 62 and 94%. CONCLUSIONS: Among children with CSF pleocytosis, a prediction model based exclusively on age, CSF total protein and CSF neutrophils differentiates accurately between acute bacterial and viral meningitis.     

Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis

Because interleukin-1 beta (IL-1 beta) and cachectin (tumor necrosis factor) are thought to mediate the body's response to microbial invasion, we measured IL-1 beta and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF1; 18 to 30 hours later, CSF2) from 106 infants and children with bacterial meningitis. In CSF1, IL-1 beta was detected in 95% of samples; the mean (+/- 1 SD) concentration was 944 +/- 1293 pg/ml. Patients with CSF1 IL-1 beta concentrations greater than or equal to 500 pg/ml were more likely to have neurologic sequelae (p = 0.001). Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml. In CSF2 the mean IL-1 beta concentration was 135 +/- 343 pg/ml, and IL-1 beta concentrations correlated significantly with CSF2 leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF2 specimens of 53 of 106 patients, with a mean concentration of 21 +/- 65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1 beta and higher glucose and lower lactate concentrations in CSF2, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p less than or equal to 0.002). Our data suggest a possible role of IL-1 beta and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.     

A case of bacterial meningitis complicated by posttraumatic cerebrospinal fluid rhinorrhea

This paper reports an 11 year old boy with bacterial meningitis accompanied by post-traumatic cerebrospinal fluid (CSF) rhinorrhea. Streptococcus pneumoniae was cultured from CSF. The clinical course was very rapid before admission and his age relatively high for usual bacterial meningitis. Consequently, we examined the cause in detail. Immunological findings were within normal limits. Although routine graphic examinations, such as cranial X-ray photography, horizontal cranial computed tomography (CT) and magnetic resonance imaging, could not demonstrate a bone defect, both coronal thin-section cranial CT scanning and radioactive isotope counting by means of cotton packed into the nasal cavity were useful for detecting CSF rhinorrhea. In a case of atypical meningitis, the past history should be examined with caution and coronal thin-section CT should be performed.     

Cerebrospinal fluid and serum lysozyme activity in bacterial and viral meningitis

Cerebrospinal fluid (CSF) and serum lysozyme concentrations were determined in infants and children with and without acute infectious disease of the central nervous system. Serum lysozyme values from patients with bacterial and viral meningitis were found within the normal range. Lysozyme activity was absent or very low (below 0.5 microgram/ml) in normal CSF. High levels (4-12 microgram/ml) in patients with viral meningitis. A decrease of the lysozyme activity coincided with the clinical improvement of the bacterial meningitis. The lysozyme activity in CSF should be of significant value in detecting an inflammatory disease of the central nervous system.     

Quantitative chloramphenicol detection in serum and cerebrospinal fluid of infants with bacterial meningitis

Twenty-six meningitic infants aged less than one year were administered daily oral or intravenous doses from 44 to 170 mg chloramphenicol per kg body weight. Serum levels measured were 5.4 to 55.0 micrograms.ml-1, and CSF concentrations from 0.9 to 20.2 micrograms.ml-1 were noted. Since, in particular for younger infants, (i) there is no clear relationship between dose and blood level and (ii) one cannot unambiguously infer the CSF concentration from the blood level we recommend that initial doses for meningitic infants be chosen according to age-adjusted dosage instructions and, from day 2 onwards, doses be corrected as a function of CSF and blood levels (CSF greater than 10 micrograms.ml-1 and serum less than 50 micrograms.ml-1).     

相关蛋白D的变化病毒性脑炎患儿血清和脑脊液中肺表面活性物质

目的：探讨病毒性脑炎(VE)患儿血清和脑脊液中肺表面活性物质相关蛋白D(SP-D)的变化。方法采用酶联免疫吸附试验双抗体夹心法分别检测30例VE患儿急性期及恢复期以及12例非脑炎儿童血清和脑脊液中的SP-D,并进行比较分。结果 VE患儿急性期、恢复期以及对照组之间血清和脑脊液SP-D水平差异有统计学意义(F=103.58、118.15,P均<0.01)。其中,VE急性期、恢复期患儿的血清和脑脊液SP-D水平均低于对照组,差异有统计学意义(P<0.01);VE恢复期血清和脑脊液SP-D水平较VE急性期有所提高,差异有统计学意义(P均<0.01)。VE患儿脑脊液中SP-D水平与脑脊液有核细胞数呈负弱相关(r=－0.317,P=0.014)。结论 SP-D可能参与病毒性脑炎的发病过程,检测血清和脑脊液中的SP-D对VE诊断具有一定的价值。     

Relevance of common tests of cerebrospinal fluid in screening for bacterial meningitis

This study tests the hypothesis that if cerebrospinal fluid (CSF) has a nucleated blood cell count (NucBC) of less than 6/mm3, CSF tests other than bacterial culture need not be performed to exclude the diagnosis of bacterial meningitis in patients not receiving antimicrobial agents. The results of tests performed on the first specimen of CSF obtained for a given hospital visit from children younger than 3 years of age, exclusive of newborn infants admitted to the hospital on their date of birth, were analyzed. Of 3356 CSF specimens evaluated, 122 were from patients with bacterial meningitis; 460 specimens were analyzed separately because the erythrocyte count was greater than 1000/mm3. A negative CSF screening test result was defined as a CSF NucBC less than 6/mm3. In facilitating the diagnosis of bacterial meningitis, this screening test had a sensitivity of 98.4%, a specificity of 75.2%, and a negative predictive value of 99.9%. The other CSF tests varied widely in screening effectiveness: a Gram-stained smear had a sensitivity of 53% and a specificity of 97%. Receiver operating characteristic curve analysis was used to assess the screening relevance of CSF tests. The CSF NucBC and CSF segmented NucBC performed indistinguishably and superiorly compared with the CSF protein or glucose concentration and the ratio of CSF glucose to serum glucose concentration. Logistic regression analysis showed that the NucBC alone is superior to any combination of the other CSF tests. In a prospective study of 215 children younger than 3 years of age undergoing a lumbar puncture in our emergency department, 85% had empiric criteria identifying them as appropriate for an abbreviated CSF evaluation. The CSF NucBC was less than 6/mm3 in 70% of the 181 patients who would have been eligible for an abbreviated CSF evaluation. These data suggest that a strategy for the sequential testing of CSF could be adopted that would exclude unnecessary determinations and thereby save time, effort, and health care dollars.     

Delayed cerebrospinal fluid sterilization and adverse outcome of bacterial meningitis in infants and children

To determine the clinical importance of CSF cultures that are persistently positive for pathogens in patients treated for meningitis with the new cephalosporins, the records of 301 infants and children with bacterial meningitis enrolled prospectively in four clinical efficacy trials of cefuroxime or ceftriaxone therapy were reviewed. CSF culture results were positive for 20 patients and they were sterile at 18 to 36 hours after start of therapy for 281 patients. Seizures, subdural effusions, and hemiparesis were found significantly more often during hospitalization in those with delayed sterilization of CSF. Children with persistently positive cultures had a significantly higher incidence of neurologic abnormalities at the time of hospital discharge (45% v 19%) and at follow-up (41% v 13%) and of moderate to profound hearing impairment (35% v 15%) than did those with prompt sterilization of CSF. Repeat CSF examination is a useful prognostic indicator in infants and young children with bacterial meningitis.     

1H-NMR spectroscopy of cerebrospinal fluid of fetal sheep during hypoxia-induced acidemia and recovery

The purpose of the study was to investigate the sequence of processes occurring during and after hypoxia-induced acidemia. We used proton nuclear magnetic resonance spectroscopy, which provides an overview of metabolites in cerebrospinal fluid (CSF), reflecting neuronal metabolism and damage. The pathophysiological condition of acute fetal asphyxia was mimicked by reducing maternal uterine blood flow in 14 unanesthetized pregnant ewes. CSF metabolites were measured during hypoxia-induced acidemia, and during the following recovery period, including the periods at 24 and 48 h after the hypoxic insult. Maximum values of the following CSF metabolites were reached during severe hypoxia (pH 相似文献   

Diffusion of moxalactam into the cerebrospinal fluid in children with bacterial meningitis

We studied the penetration of moxalactam into the cerebrospinal fluid of 16 children (age range one month to 4 1/2 years) who were being treated for bacterial meningitis. Two hours after single intravenous doses of 15 or 25 mg/kg, moxalactam was detectable in the CSF in only one of 11 instances; however, following three doses (50 mg/kg each) moxalactam was detectable in eight of 17 instances. In these eight instances CSF concentrations of moxalactam ranged between 1.5 and 18.9 micrograms/ml (mean 7.7) and the CSF/plasma ratio ranged from 2.6 to 36% (mean 17.7). There was no relation between the stage of meningitis or the CSF cell count and the diffusion of the drug into the CSF. However, the diffusion of the drug significantly correlated with the CSF protein content. In view of the unpredictability of moxalactam penetration into CSF, caution should be exercised in using it alone in the treatment of meningitis.     

Reovirus type 2 isolated from cerebrospinal fluid

An 8-week-old female infant presented with a history of active varicella complicated by Escherichia coli sepsis, oral thrush, hypoalbuminemia, intermittent fevers, diarrhea and feeding intolerance. Rhesus monkey kidney cells inoculated with cerebrospinal fluid revealed reovirus-like particles by electron microscopy. Virus neutralization and RNA-gel electrophoresis studies identified the isolated pathogen as reovirus serotype 2. This report represents one of only a few to isolate reovirus from the central nervous system in humans.     

细菌性脑膜炎患儿脑脊液一氧化氮变化的研究

目的观察细菌性脑膜炎患儿脑脊液一氧化氮(NO)的变化及地塞米松对其的影响.方法应用Griess法和氨基酸自动分析仪检测23例细菌性脑膜炎患儿脑脊液中NO代谢终产物--亚硝酸盐和NO前体--L-精氨酸的浓度,并将31例无神经系统疾病患儿的脑脊液作为对照组.结果(1)治疗前,细菌性脑膜炎患儿脑脊液亚硝酸盐浓度[(10.76±4.09)μnol/L]明显高于对照组[(2.69±1.20)μnol/L],差异有显著性(t1=10.41,P＜0.01);经治疗后,脑脊液亚硝酸盐浓度渐下降.脑脊液指标恢复正常后,亚硝酸盐浓度[(3.00±1.16)μmol/L]与对照组差异无显著性(t=1.24,P＞0.05).(2)23例细菌性脑膜炎患儿中,14例单用抗生素治疗,其余9例在抗生素治疗的基础上,加用地塞米松治疗.抗生素+地塞米松治疗组脑脊液亚硝酸盐浓度[(5.92±1.90)μnol/L]显著低于单用抗生素组[(8.86±3.50)μnol/L],差异有显著性(t=2.30,P＜0.05).(3)细菌性脑膜炎患儿治疗前脑脊液L-精氨酸浓度[(12±6)μmol/L]显著低于对照组[(17±8)μnol/L],差异有显著性(t＝2.29,P＜0.05).结论NO参与了细菌性脑膜炎的病理过程,而地塞米松能部分抑制NO的过度产生.