Cerebrospinal fluid concentrations of interleukin-1 beta, tumour necrosis factor-alpha, and interferon gamma in bacterial meningitis

To investigate the role of the inflammatory cytokines, the cerebrospinal fluid concentrations of interleukin (IL)-1 beta, tumour necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were measured in 11 children with bacterial meningitis and two with mycoplasmic meningoencephalitis and compared with those in 50 children with aseptic meningitis and 15 with non-pleocytotic cerebrospinal fluid. Concentrations of IL-1 beta and TNF-alpha were each significantly higher in the cerebrospinal fluid of patients with bacterial meningitis than in those with aseptic meningitis or those with non-pleocytotic cerebrospinal fluid. IFN-gamma was detected at low concentrations in the cerebrospinal fluid of only 2/11 of those with bacterial meningitis. On the other hand, the IFN-gamma concentration was the highest in the cerebrospinal fluid of patients with aseptic meningitis. These results suggest that the inflammatory cytokines are differently released in the intrathecal space infected with viruses or bacteria.     

Cerebrospinal fluid concentrations of interleukin-1 beta, tumour necrosis factor-alpha, and interferon gamma in bacterial meningitis.

To investigate the role of the inflammatory cytokines, the cerebrospinal fluid concentrations of interleukin (IL)-1 beta, tumour necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were measured in 11 children with bacterial meningitis and two with mycoplasmic meningoencephalitis and compared with those in 50 children with aseptic meningitis and 15 with non-pleocytotic cerebrospinal fluid. Concentrations of IL-1 beta and TNF-alpha were each significantly higher in the cerebrospinal fluid of patients with bacterial meningitis than in those with aseptic meningitis or those with non-pleocytotic cerebrospinal fluid. IFN-gamma was detected at low concentrations in the cerebrospinal fluid of only 2/11 of those with bacterial meningitis. On the other hand, the IFN-gamma concentration was the highest in the cerebrospinal fluid of patients with aseptic meningitis. These results suggest that the inflammatory cytokines are differently released in the intrathecal space infected with viruses or bacteria.     

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.     

Predictive value of plasma and cerebrospinal fluid tumour necrosis factor-alpha and interleukin-1 beta concentrations on outcome of full term infants with hypoxic-ischaemic encephalopathy

AIM: To determine the predictive value of plasma and cerebrospinal fluid (CSF) tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) concentrations on the outcome of hypoxic-ischaemic encephalopathy (HIE) in full term infants. METHODS: Thirty term infants with HIE were included in the study. HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF were obtained within the first 24 hours of life and stored until assay. Five infants died soon after hypoxic insult. Neurological examinations and Denver Developmental Screening Test (DDST) were performed at 12 months in the survivors. RESULTS: At the age of 12 months neurological examination and DDST showed that 11 infants were normal; 14 had abnormal neurological findings and/or an abnormal DDST result. Eleven normal infants were classified as group 1 and 19 infants (14 with abnormal neurological findings and/or an abnormal DDST and five who died) as group 2. CSF IL-1 beta and TNF-alpha concentrations in group 2 were significantly higher than those in group 1. Plasma IL-1 beta and TNF-alpha concentrations were not significantly different between the two groups. IL-1 beta, but not TNF-alpha concentrations, in group 2 were even higher than those in group 1, although non-survivors were excluded from group 2. When the patients were evaluated according to the stages of Sarnat, the difference in the three groups was again significant. Patients whose CSF samples were taken within 6 hours of the hypoxic insult had higher IL-1 beta and TNF-alpha concentrations than the patients whose samples were taken after 6 hours. CONCLUSIONS: Both cytokines probably contribute to the damage sustained by the central nervous system after hypoxic insult. IL-1 beta seems to be a better predictor of HIE than TNF-alpha.     

CSF interleukin-1 beta, tumor necrosis factor-alpha and free radicals production in relation to clinical outcome in acute bacterial meningitis

OBJECTIVE: To study the relationship of CSF IL-1 beta and TNF-alpha with free radicals in acute bacterial meningitis (ABM) and to evaluate the clinical outcome in relation to the levels of these cytokines and free radicals in CSF. DESIGN: Prospective with controls. SETTING: Referral unit of a teaching hospital. METHODS: 32 children between 3m-12 yrs of age with proven acute bacterial meningitis comprised the study group. In the control group, 20 children with febrile seizures were included. CSF cytokines- Interleukin Ib and tumour necrosis factor a,free radicals O(2)-, H(2)O(2) and enzymes SOD and CPK were measured in all the children. RESULTS: CSF IL-Ib and TNF-a concentration were markedly elevated in children with ABM (441.5 +/- 216.1 pg/ml, and 1009 +/- 529.1 pg/ml, respectively) as compared to controls (52.67 +/- 6.92 pg/ml, and 86.42 +/- 16.24 pg/ml) (p <0.0001). Free radicals viz., superoxide anion, hydrogen peroxide production and enzymes creatinine phosphokinase and superoxide dismutase were also significantly elevated in ABM as compared to controls. There was direct correlation of CSF cytokines with CSF cytology, protein and free radicals production in ABM. Patients who expired or had neurological sequelae had markedly elevated concentrations of cytokines and free radicals. CONCLUSION: IL-I beta, TNF-alpha and free radicals are significantly elevated in CSF of patients with ABM. The concentration of these cytokines correlated well with free radical production, and with routinely measured CSF parameters and had a direct bearing on outcome of ABM     

Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis

Endotoxin concentrations were measured in paired samples of cerebrospinal fluid from 38 patients with Haemophilus influenzae type b meningitis. On admission, the median concentration of endotoxin in cerebrospinal fluid was 104 ng/mL and decreased rapidly in follow-up samples. From 17 to 48 hours after admission, 50% of the patients had concentrations of less than 1 ng/mL. Endotoxin concentrations correlated significantly with concentrations of interleukin 1 beta, protein, and glucose in cerebrospinal fluid, duration of secondary fever, and neurologic abnormalities during hospitalization and on follow-up examinations. Twenty-eight percent of patients with endotoxin concentrations of 100 ng/mL or more on admission had long-term complications, compared with none of those with lower endotoxin concentrations (relative risk, 2.31; 95% confidence interval, 1.53 to 3.48). These results indicate that quantitation of endotoxin in cerebrospinal fluid could be a valuable aid in identifying those children at increased risk of complications during Haemophilus influenzae type b meningitis and provide additional evidence that the Haemophilus influenzae type b meningitis lipo-oligosaccharide is important in the pathogenesis of meningitis.     

Cerebrospinal fluid concentrations of alpha-melanocyte-stimulating hormone in bacterial and aseptic meningitis

-Melanocyte-stimulating hormone (-MSH) has potent anti-inflammatory effects in several experimental models of inflammation. It inhibits both the actions and production of proinflammatory cytokines and neutrophil migration. We investigated whether -MSH in cerebrospinal fluid (CSF) increases during the acute stage in patients with bacterial and aseptic meningitis by measuring -MSH in CSF via radioimmunoassay. The -MSH concentrations in CSF from the children with bacterial meningitis who survived (n = 8), those with aseptic meningitis (n = 16), and the control subjects (n = 23) were all below the detection limit. However, CSF -MSH was elevated in four of the five children with bacterial meningitis who had neurological sequelae. We speculate that elevated -MSH levels in CSF during acute bacterial meningitis reflect negative feedback in response to severe inflammation associated with neurological sequelae induced by proinflammatory cytokines. Conclusion: CSF -MSH is elevated in children with severe bacterial meningitis who had neurological sequelae.     

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.     

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.     

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).     

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.     

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.     

Cerebrospinal fluid interleukin 1-beta and tumor necrosis factor concentrations and outcome from neonatal gram-negative enteric bacillary meningitis

Concentrations of interleukin 1-beta and tumor necrosis factor in cerebrospinal fluid (CSF) of 42 neonates with Gram-negative enteric bacillary meningitis were determined and correlated with outcome and other CSF indices. At the time of diagnosis interleukin 1-beta was detected in CSF of 40 infants and peak concentrations correlated significantly with outcome from disease. Days of interleukin 1-beta concentrations of greater than 200 pg/ml or greater than or equal to 20 pg/ml were significantly correlated with days that CSF cultures were positive and that K1 antigen and endotoxin were detected in CSF. Tumor necrosis factor activity was detected in CSF of 25 of 27 infants; there was no correlation between outcome and CSF tumor necrosis factor concentrations. The results provide a possible rationale for therapeutic intervention to improve outcome.     

Diagnostic accuracy of cerebrospinal fluid gram stain in children with suspected bacterial meningitis

This cross-sectional study included 1938 children undergoing lumbar puncture; 21 (1.1%) cases were classified as definite (n = 17) or probable (n = 4) bacterial meningitis. Gram stain sensitivity was 94.1% (95% confidence interval, 71.3%-99.9%) for those with definite meningitis; the positive predictive value was 47.1% (95% confidence interval, 29.8%-64.9%). The sensitivity was 95.2% for those with definite or probable meningitis. Antibiotic pretreatment did not affect results.     

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.     

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。