Value of cerebrospinal fluid leukocyte aggregation in distinguishing the causes of meningitis in children

BACKGROUND: Current laboratory tests often cannot distinguish between bacterial and aseptic meningitis rapidly and accurately. The ability to make a prompt diagnosis has important implications for the management and outcome of children with meningitis. The observation that leukocytes aggregate in the cerebrospinal fluid (CSF) has been previously reported, and it has been advocated as a reliable method to distinguish the causes of meningitis in children. OBJECTIVE: To investigate the utility of CSF leukocyte aggregation as a screening test to distinguish between bacterial and aseptic meningitis. METHODS: We compared the clinical and laboratory indices of 109 prospectively enrolled patients with meningitis (67 bacterial, 23 viral, 19 undefined etiology) and evaluated the validity of the CSF leukocyte aggregation test. The predefined leukocyte aggregation scores (LAS) were compared among the types of meningitis, and correlations with other markers of inflammation were calculated. RESULTS: The median LAS was significantly higher (P < 0.001) in the bacterial (32.1%; range, 0 to 84.1%) than in the viral (0%; range, 0 to 16.6%) or undefined (0%; range, 0 to 20.7%) groups. The optimal sensitivity of the leukocyte aggregation test, 98.5 to 92.5%, was demonstrated with LAS values of 0 to 3%. The corresponding specificity was 64.3 to 88.1%. The peripheral white blood cell (WBC) count, serum C-reactive protein, CSF WBC count, blood culture, CSF Gram stain and CSF culture were inferior to the LAS as screening tests when compared individually. The LAS was as effective as CSF protein, TNF-alpha, IL-1-beta, IL-6 and IL-8 to predict bacterial meningitis. In a logistic regression model that included routine laboratory tests, the best predictor of bacterial meningitis was the LAS (odds ratio, 1.6 to 3.7). Significant correlations were demonstrated between the LAS and CSF protein, CSF WBC count, IL-1-beta, IL-6 and IL-8. Duration of symptoms before diagnosis, pretreatment with antibiotics, HIV-1 infection status and CSF red blood cell count did not significantly alter the LAS. CONCLUSIONS: There is no single test to diagnose the etiology of meningitis in children promptly and accurately. The finding of leukocyte aggregation in CSF might be of value as a sensitive adjunctive screening tool for the timely diagnosis of bacterial meningitis, recognizing that it has low specificity and potential practical limitations.     

血降钙素原在儿童化脓性脑膜炎与病毒性脑膜炎中的变化

目的：化脓性脑膜炎病原学检出率较低,尤其脑脊液改变不典型时给临床诊断带来困难。已证实血降钙素原(PCT)测定对鉴别细菌与病毒感染有重要价值,但在化脓性脑膜炎与病毒性脑膜炎的鉴别诊断方面与CRP、血沉比较孰优孰劣未见报道,另外诊断化脓性脑膜炎时PCT临界值的确定也未见报道。该文通过血PCT测定并与CRP、血沉比较探讨其对儿童化脓性脑膜炎与病毒性脑膜炎的鉴别诊断意义。方法：用免疫荧光法测定了41例急性脑膜炎患儿血PCT(其中化脓性脑膜炎18例,病毒性脑膜炎23例),同时测定血CRP、血沉。结果：化脓性脑膜炎组PCT,CRP及血沉分别为51.73±30.75μg/L,182.36±54.5mg/L和50.44±8.95mm/h;明显高于病毒性脑膜炎组0.84±0.99μg/L,8.90±10.66mg/L和16.75±13.23mm/h(P<0.01),受试者工作特征曲线下面积PCT为0.984(95%可信区间0.953～1.013),而CRP为0.983(95%可信区间0.954～1.012),二者比较差异无显著性(P>0.05)。有2例病毒性脑膜炎PCT值高于0.5μg/L,而化脓性脑膜炎病人均高于此值。结论：血PCT同CRP在儿童化脓性脑膜炎与病毒性脑膜炎的鉴别诊断方面有重要参考价值,优于血沉。     

Cerebrospinal fluid C-reactive protein in meningitis: diagnostic value and pathophysiology

We examined the diagnostic value of C-reactive protein (CRP) in cerebrospinal fluid (CSF) on initial lumbar puncture in a prospective study including 126 patients (30 neonates, 96 infants and children) suspected of having meningitis. Twenty patients were considered to have bacterial and 25 were considered to have viral meningitis. In infants and children, a retrospectively chosen cut-off CRP titre of 4 (i.e. 0.4 mg/l CRP) had a sensitivity of 100% and a specificity of 94% for differentiating bacterial meningitis from both viral meningitis and normal. It was a more sensitive and selective test for differentiating bacterial from viral meningitis on initial CSF examination than was the CSF leucocyte count, glucose concentration or protein concentration. In neonates, no such cut-off CRP titre could be found, presumably due to the immaturity of the blood-CSF-barrier (Bl-CSF-B) during the first weeks of life. In a parallel study including a non-selected group of 13 infants and children (4 without, 9 with bacterial meningitis), the serum/CSF CRP concentration ratios were determined and inserted in the individual Bl-CSF-B diagrams according to Felgenhauer. The results were fully consistent with the hypothesis that the CRP concentration in CSF reflects the normal permeability characteristics of the Bl-CSF-B, or the degree of its impairment. Based on our results, we recommend the CSF CRP estimation in the routine evaluation of infants and children suspected of having meningitis.Abbreviations CRP C-reactive protein - CSF cerebrospinal fluid - Bl-CSF-B blood-cerebrospinal fluid-barrier - Qp Concentration ratio in serum/CSF of a given protein P - IgG immunoglobulin G - R (Å) hydrodynamic radius in ångström     

Impact of haemophilus influenzae type b conjugate vaccine in South Africa and Argentina

INTRODUCTION: Haemophilus influenzae type b (Hib) persists as a major cause of pediatric meningitis and pneumonia in developing countries in which Hib conjugate vaccines are not used. Demonstration of decreases in severe Hib disease after countries introduce Hib conjugate vaccine will help justify the resources necessary to purchase and provide the vaccine. Because surveillance for culture-confirmed Hib meningitis is not available in many countries, alternative means to measure the impact of Hib conjugate vaccine would be useful. METHODS: Laboratory records from the years before and after introduction of the Hib conjugate vaccine were reviewed at 4 hospitals, 2 in Argentina and 2 in South Africa. Potential indicators of bacterial meningitis including cerebrospinal fluid (CSF) culture, white blood cell count, appearance, protein and glucose were recorded. RESULTS: After introduction of Hib conjugate vaccine, culture-confirmed Hib meningitis declined significantly at 3 of 4 hospitals (2 in Argentina and 1 in South Africa). In the same 3 hospitals, there was a significant decline after vaccine introduction in some of the following CSF indicators of bacterial meningitis: proportion of CSF specimens with white blood cell count > or = 100 x 10(6)/L, 500 x 10(6)/L and 1,000 x 10(6)/L; glucose <40 mg/dL; protein >100 mg/dL; and turbid appearance. CONCLUSIONS: Culture-confirmed Hib meningitis declined at 3 of the 4 hospitals after Hib vaccine introduction. Surrogate indicators of bacterial meningitis also declined and might be useful measures of Hib conjugate vaccine impact at hospitals where capacity to culture Hib is not available.     

Test characteristics and interpretation of cerebrospinal fluid gram stain in children

BACKGROUND: Few data exist regarding the test characteristics of cerebrospinal fluid (CSF) Gram stain among children at risk for bacterial meningitis, especially the rate of false positive Gram stain. METHODS: We conducted a retrospective cohort study of children seen in the emergency department of Children's Hospital Boston who had CSF obtained between December 1992 and September 2005. Patients who had ventricular shunts, as well as those who received antibiotics before CSF was obtained were excluded. Test characteristics of CSF Gram stain were assessed using CSF culture as the criterion standard. Patients were considered to have bacterial meningitis if there was either: (1) growth of a pathogen, or (2) growth of a possible pathogen noted on the final CSF culture report and the patient was treated with a course of parenteral antibiotics for 7 days or more without other indication. RESULTS: A total of 17,569 eligible CSF specimens were collected among 16,036 patients during the 13-year study period. The median age of study subjects was 74 days. Seventy CSF specimens (0.4%) had organisms detected on Gram stain. The overall sensitivity of Gram stain to detect bacterial meningitis was 67% [42 of 63; 95% confidence interval (CI): 54-78] with a positive predictive value of 60% (42 of 70; 95% CI: 48-71). Most patients without bacterial meningitis have negative Gram stain [specificity 99.9% (17,478 of 17,506; 95% CI: 99.8-99.9)] with a negative predictive value of 99.9 (17,478 of 17,499; 95% CI: 99.8-99.9). CONCLUSIONS: CSF Gram stain is appropriately used by physicians in risk stratification for the diagnosis and empiric treatment of bacterial meningitis in children. Although a positive Gram stain result greatly increases the likelihood of bacterial meningitis; the result may be because of contamination or misinterpretation in 40% of cases and should not, by itself, result in a full treatment course for bacterial meningitis.     

C-reactive protein and bacterial meningitis

We have studied prospectively the C-reactive protein values in the cerebrospinal fluid of 54 patients with bacterial meningitis, tuberculous meningitis, and severe malarial infection and convulsions without infections of the central nervous system. CSF CRP above 1 mg/l was observed in 23 out of 28 patients with bacterial meningitis (sensitivity of 82%). The specificity was 73% at the 1 mg/l level. Five out of 19 patients with severe malarial infection had CSF CRP levels above 1 mg/l. Two patients with TB meningitis were also studied. Both of them had CSF CRP above 1 mg/l. Five patients with febrile convulsions or sepsis without meningitis had CSF CRP below 1 mg/l. It is concluded that CSF CRP would not be used as a useful discriminatory test in areas where malaria and TB meningitis are common.     

Absent or minimal cerebrospinal fluid abnormalities in Haemophilus influenzae meningitis

A case of Haemophilus influenzae type b (Hib) meningitis in which the diagnosis and treatment were delayed because of normal cerebrospinal fluid analysis is presented. A retrospective review was conducted at two children's hospitals to determine the frequency and clinical characteristics of patients with Hib meningitis whose spinal fluid had a normal total white blood cell count, normal chemistries, and negative Gram stain, but subsequent growth of Hib in culture. Of 379 cases of Hib meningitis, two had completely normal CSF, and two had CSF containing small numbers of polymorphonuclear cells as the sole abnormality. In three of the four cases, the duration of symptoms was less than 24 hours, and appropriate therapy was significantly delayed because of benign-appearing CSF. Normal CSF cell counts, chemistries, and Gram stain do not exclude the possibility of bacterial meningitis, and one should remain suspicious when a child has clinical findings suggesting meningitis.     

Cerebrospinal fluid lactic acidosis in bacterial meningitis.

A rapid, microenzymatic method was used to measure cerebrospinal fluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinal fluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinal fluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae.     

Bacterial antigen detection test in meningitis

Objective : To evaluate the role of bacterial antigen detection test in cerebrospinal fluid (CSF) for a rapid etiological diagnosis of bacterial meningitis.Methods : The study included 36 cases of bacterial meningitis and 14 controls. Latex particle agglutination test (LPA test) for detection of bacterial antigen was done in the CSF using slidex meningitis kit (Biomeriux, France).Results : Using LPA test, an etiological diagnosis could be made in 83% cases of bacterial meningitis. In contrast, CSF Gram stain and culture showed 36% and 6% positivity, respectively. The sensitivity and specificity of LPA test were 83% and 100%, respectively. The common etiological organisms were S.pneumoniae, H. influenzae type b andN. meningitidis A. S. pneumoniae was encountered in all age groups whileH. influenzae type b was found only below one year of age.Conclusions : LPA test is a rapid and superior diagnostic tool as compared to CSF Gram stain and culture. The study recommends LPA test as an adjunct laboratory test for rapid etioiogical diagnosis of bacterial meningitis for prompt institution of proper antibiotics.     

Serum C-reactive protein in the differential diagnosis of childhood meningitis

BACKGROUND: Although determination of serum C-reactive protein (CRP) is considered one of the most useful tests for differentiating between bacterial and aseptic meningitis, its diagnostic accuracy in comparison with other laboratory parameters is yet to be further evaluated. METHODS: A total of 192 pediatric cases, aged between 2 months and 14 years, comprising patients with bacterial meningitis (n = 66) and aseptic meningitis (n = 126), were retrospectively analyzed on the basis of data from the initial examination. The area under the best fit binormal curve of the receiver operating characteristics (Az) for CRP was determined and compared with that for several other analytic parameters, including white blood cell count and erythrocyte sedimentation rate of peripheral blood, standard cerebrospinal fluid analysis variables and the combination test (probability of acute bacterial meningitis (pABM)) derived from Hoen's model. RESULTS: Compared with each of the other variables, the Az for serum CRP (0.97 +/- 0.02) was found to be significantly greater (P < 0.01) for all except pABM (0.99 +/- 0.01; P > 0.05). False-negative cases among the CRP test results were found to have been examined too early. CONCLUSIONS: The diagnostic accuracy of a single CRP determination was found to be equivalent to that of the most effective combination test. Patients with meningitis in whom serum CRP values are determined at least 12 h after the onset of fever and are < 2 mg/dL are far less likely to have bacterial meningitis.     

Seasonal outbreak of enteroviral meningitis during summer 2005: experience of a French pediatric unit]

OBJECTIVE: To describe the clinical and biological characteristics of children presenting with enteroviral (EV) meningitis in a French paediatric unit during summer 2005. METHODS: Retrospective study of children with EV meningitis from May to September 2005, diagnosed by PCR and/or viral culture in cerebrospinal fluid (CSF), serum or throat. RESULTS: We reported 99 cases of EV meningitis (96 confirmed and 3 probable). The sex ratio was 2/1, and the median age was 5 years. Peak incidence was reached during the second week of July. The predominant symptom was meningism. ENT (16%), digestive (10%), cutaneous (15%) or respiratory (4%) symptoms were rare. Blood leucocyte count found a predominance of neutrophils (73%), and lymphopenia in half of the children. The mean value of CRP was 25,5 mg/l. The median leukocyte count in CSF was 65 cells/mm(3), with a prevalence of neutrophils in 60% of cases. Pleiocytosis was absent in 20 children. CSF protein level was increased in 20% of cases. The rate of hospitalization was 57,5%. Intravenous antibiotic treatment, initiated among 18 patients, was stopped in 66,6% of the cases on reception of PCR result. The latter result was obtained in 2,3 days on average. CONCLUSION: The epidemic of 2005 EV meningitis was as widespread as that of summer 2000. Characteristics of these meningitis are strong proportion of CSF without pleiocytose and high prevalence of neutrophils in blood and CSF.     

Neonatal Staphylococcus epidermidis meningitis with unremarkable CSF examination results

We identified 10 infants (mean +/- SD birth weight, 1000 +/- 500 g; gestation, 29 +/- 3 weeks; postnatal age, 24 +/- 19 days) who had Staphylococcus epidermidis meningitis despite unremarkable cerebrospinal fluid (CSF) blood cell counts and glucose and protein levels. Staphylococcus epidermidis meningitis was diagnosed if all the following criteria were satisfied: (1) a CSF culture positive for S epidermidis within 48 hours, (2) a blood culture positive for S epidermidis with antibiotic sensitivities identical to those of the CSF isolate, and (3) clinical symptomatology. Lumbar puncture yielded white blood cell counts lower than 10 x 10(6)/L in 8 infants. Two subjects had CSF white blood cell counts of 11 x 10(6)/L and 14 x 10(6)/L. Cerebrospinal fluid glucose (2.8 +/- 0.9 mmol/L) and protein (1.15 +/- 0.32 g/L) concentrations were also unremarkable. Infants were treated with parenteral antibiotics for 19 +/- 5 days. There was no mortality or short-term morbidity. Staphylococcus epidermidis is a recognized cause of nosocomial meningitis in low-birth-weight infants and frequently occurs without CSF abnormalities.     

Utility of the serum C-reactive protein for detection of occult bacterial infection in children

OBJECTIVE: To assess the utility of serum C-reactive protein (CRP) as a screen for occult bacterial infection in children. METHODS: Febrile children ages 3 to 36 months who visited an urban children's hospital emergency department and received a complete blood cell count and blood culture as part of their evaluation were prospectively enrolled from February 2, 2000, through May 30, 2001. Informed consent was obtained for the withdrawal of an additional 1-mL aliquot of blood for use in CRP evaluation. Logistic regression and receiver operator characteristic (ROC) curves were modeled for each predictor to identify optimal test values, and were compared using likelihood ratio tests. RESULTS: Two hundred fifty-six patients were included in the analysis, with a median age of 15.3 months (range, 3.1-35.2 months) and median temperature at triage 40.0 degrees C (range, 39.0 degrees C-41.3 degrees C). Twenty-nine (11.3%) cases of occult bacterial infection (OBI) were identified, including 17 cases of pneumonia, 9 cases of urinary tract infection, and 3 cases of bacteremia. The median white blood cell count in this data set was 12.9 x 10(3)/ micro L [corrected] (range, 3.6-39.1 x10(3)/ micro L) [corrected], the median absolute neutrophil count (ANC) was 7.12 x 10(3)/L [corrected] (range, 0.56-28.16 x10(3)/L) [corrected], and the median CRP level was 1.7 mg/dL (range, 0.2-43.3 mg/dL). The optimal cut-off point for CRP in this data set (4.4 mg/dL) achieved a sensitivity of 63% and a specificity of 81% for detection of OBI in this population. Comparing models using cut-off values from individual laboratory predictors (ANC, white blood cell count, and CRP) that maximized sensitivity and specificity revealed that a model using an ANC of 10.6 x10(3)/L [corrected] (sensitivity, 69%; specificity, 79%) was the best predictive model. Adding CRP to the model insignificantly increased sensitivity to 79%, while significantly decreasing specificity to 50%. Active monitoring of emergency department blood cultures drawn during the study period from children between 3 and 36 months of age showed an overall bacteremia rate of 1.1% during this period. CONCLUSIONS: An ANC cut-off point of 10.6 x10(3)/L [corrected] offers the best predictive model for detection of occult bacterial infection using a single test. The addition of CRP to ANC adds little diagnostic utility. Furthermore, the lowered incidence of occult bacteremia in our population supports a decrease in the use of diagnostic screening in this population.     

Procalcitonin and viral meningitis: reduction of unnecessary antibiotics by measurement during an outbreak]

OBJECTIVE: Viral meningitis are often treated with antibiotics in emergency because routine analysis of CSF is not always efficient for distinguishing between viral and bacterial infection. The aim of the study was to evaluate the usefulness of procalcitonin (PCT) to reduce antibiotic treatments. METHODS AND RESULTS: A blood PCT level < 0.5 ng/mL was prospectively used for the diagnosis of viral origin of meningitis in 58 patients (two months-14 years), in which enterovirus was isolated by culture or PCR during an outbreak (May-June 2000). CSF cells range was 10 to 2800/mL (m: 244), PMN 5 to 2464/mL and CSF proteins range was 0.19 to 0.92 mg/dL (m: 0.37). Seventeen patients received antibiotic therapy in admission. In nine patients, PCT (dosage was routinely measured 3/week) result < 0.5 ng/mL was obtained in 24 h and in 48 h in six: treatment was then stopped and children led hospital. In two patients, PCT was > 1 ng/mL because of bacterial coinfection. CSF and PCT values were similar to those of an already published control group. CONCLUSION: PCT dosage allowed to shorten hospitalization of 4.47 (controls) to 2.06 (patients) days in patients receiving unnecessary antibiotic treatments. During this outbreak, PCT dosage allowed to reduce 40 days of hospitalization.     

A diagnostic rule for tuberculous meningitis.

Diagnostic confusion often exists between tuberculous meningitis and other meningoencephalitides. Newer diagnostic tests are unlikely to be available in many countries for some time. This study examines which clinical features and simple laboratory tests can differentiate tuberculous meningitis from other infections. Two hundred and thirty two children (110 tuberculous meningitis, 94 non-tuberculous meningitis, 28 indeterminate) with suspected meningitis and cerebrospinal fluid (CSF) pleocytosis were enrolled. Tuberculous meningitis was defined as positive CSF mycobacterial culture or acid fast bacilli stain, or basal enhancement or tuberculoma on computed tomography (CT) scan with clinical response to antituberculous treatment. Non-tuberculous meningitis was defined as positive CSF bacterial culture or Gram stain, or clinical response without antituberculous treatment. Thirty clinical/laboratory features of patients with tuberculous meningitis and non-tuberculous meningitis were compared by univariate and multiple logistic regression analysis. Five features were independently predictive of the diagnosis of tuberculous meningitis (p < 0.007): prodromal stage >/= 7 days, optic atrophy on fundal examination, focal deficit, abnormal movements, and CSF leucocytes < 50% polymorphs. When validated on another set of 128 patients, if at least one feature was present, sensitivity was 98.4% and, if three or more were present, specificity was 98.3%. This simple rule would be useful to physicians working in regions where tuberculosis is prevalent.     

Cerebrospinal fluid C-reactive protein in the laboratory diagnosis of bacterial meningitis

Samples of cerebrospinal fluid from 112 cases of suspected meningitis were tested for the presence of C-reactive protein (CRP), using a qualitative and quantitative slide test. Bacterial meningitis was confirmed in 34 patients, based on CSF and blood culture results, and/or elevated CSF white blood cell (WBC) count and typical biochemical profile. There were 8 patients with early onset, and 3 who had received prior antimicrobial therapy among the 5 neonates, 23 children, and 6 adults with bacterial meningitis. Organisms recovered from CSF, and/or blood, included Haemophilus influenzae 14, Streptococcus pneumoniae 9, Streptococcus group B-5, Staphylococcus aureus 2, E. coli 2 and Klebsiella pneumoniae 1. Slide test was positive for CRP in 33 cases, giving a sensitivity of 97% which compared favourably with elevated CSF protein 33%, decreased CFS glucose 64.7% CSF glucose/blood glucose less than 1/2, 85%, raised CSF WBC 38.2%, raised CSF PMN 61.7%, CSF culture positive 88.2%, and CSF gram-positive 82.5%. Slide test was positive for CRP in 1 of 78 CSF samples negative for bacterial meningitis, giving a specificity of 98%. It was concluded that testing of CSF for CRP is a simple, rapid and accurate method for the laboratory diagnosis of bacterial meningitis, which is particularly appropriate for areas lacking adequate laboratory facilities.     

Cerebrospinal fluid enrichment broth cultures rarely contribute to the diagnosis of bacterial meningitis

This study included children undergoing lumbar puncture in the emergency department. Bacteria were isolated from 34 (1.7%) of 1898 cerebrospinal fluid (CSF) enrichment broth cultures; 30 were contaminants. The primary CSF Gram stain was negative in all specimens with a positive enrichment broth culture. Enrichment broth cultures rarely contributed to the diagnosis of bacterial meningitis, and positive CSF enrichment broth cultures contributed to diagnostic uncertainty.     

Children with meningeal signs: predicting who needs empiric antibiotic treatment

BACKGROUND: Since delayed diagnosis and treatment of bacterial meningitis worsens patient prognosis, clinicians have a low threshold to perform a lumbar puncture or to start empiric antibiotic treatment in patients suspected of having meningitis. OBJECTIVE: To develop a decision rule, including cerebrospinal fluid (CSF) indices and clinical characteristics, to determine whether empiric antibiotic treatment should be started in children with meningeal signs. DESIGN: Multivariable logistic regression analysis of retrospectively collected data. Bacterial meningitis was defined as a CSF leukocyte count of more than 5/ micro L with positive bacterial culture findings from CSF or blood specimens. SETTING: Pediatric emergency department of a pediatric university hospital. PATIENTS: A total of 227 children (aged 1 month to 15 years) with meningeal signs. MAIN OUTCOME MEASURE: The diagnostic value of adding early obtainable CSF indices to clinical characteristics to predict bacterial meningitis. RESULTS: Independent predictors of bacterial meningitis from early obtainable CSF indices were the CSF polymorphonuclear leukocyte count and the CSF-blood glucose ratio. The diagnostic value (area under the receiver operating characteristic curve) of this CSF model was 0.93. Application of the model together with clinical characteristics could predict early the absence of bacterial meningitis in 69 (30%) of the 227 patients so that empiric antibiotic treatment could be safely withheld. CONCLUSION: A diagnostic decision rule that uses clinical characteristics at admission, the CSF polymorphonuclear leukocyte count, and the CSF-blood glucose ratio is a useful tool for deciding whether to start empiric antibiotics in children with meningeal signs.     

Cerebrospinal fluid C-reactive protein measurement--a bedside test in the rapid diagnosis of bacterial meningitis

C-reactive protein (C-RP) determinations were performed by the Latex agglutination method on the cerebrospinal fluid (CSF) samples of 212 patients with clinical features suggestive of meningitis. Patients were grouped as follows Group I: bacterial meningitis and partially treated bacterial meningitis (n = 22). Group II: viral encephalitis (n = 11). Group III: tuberculous meningitis (n = 18). Group IV: (i) febrile convulsions (n = 87); (ii) epileptic seizures (n = 70); (iii) intracranial haemorrhage (n = 4). C-RP was a better indicator of bacterial meningitis (sensitivity 91 per cent) than the Gram's stain (sensitivity 46 per cent). C-RP was positive in 91 per cent of patients in Group I, none in Groups II and III and 0.6 per cent in Group IV. C-RP determination in CSF proved to be a useful indicator of bacterial meningitis and served to distinguish it from viral encephalitis, tuberculous meningitis, febrile convulsions and other central nervous system disorders.     

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.