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.     

A clear CSF is not always a normal CSF

A normal initial cerebrospinal fluid (CSF) study has been traditionally used to exclude the potential diagnosis of bacterial meningitis. However, cases of pyogenic meningitis in the absence of CSF pleocytosis have been reported in which smears for gram stain or CSF culture revealed the diagnosis of meningitis. In the presence of clinical signs of meningitis, an abnormal initial CSF study indicates a diagnosis of bacterial meningitis but a normal result may not necessarily exclude it and therefore, should not delay early institution of appropriate antimicrobial therapy.     

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.     

The Diagnostic and Predictive Value of Cerebrospinal Fluid Lactate in Children with Meningitis

ABSTRACT. One hundred and thirty-three children with suspected meningitis aged from 11 days to 16 years were investigated with routine cerebrospinal fluid (CSF) laboratory methods: microscopy of a Gram-stained smear, bacterial culture, determination of leukocytes, lactate, and the CSF/blood glucose ratio. On the basis of bacterial cultures and clinical course, the children were classified into three groups: bacterial meningitis (n=18), aseptic meningitis (n=28), and a control group (n=87). The main intention was to study the relation between current diagnostic methods and lactate. CSF lactate levels and cell counts, related significantly (p<0.01) better to the presence of bacterial meningitis than CSF/blood glucose ratios. Lactate levels exceed 2.4 mmol/l in all children with bacterial meningitis, but in none of the control group. Of 28 children with aseptic meningitis 3 had lactate in the range 2.5-2.7 mmol/l, while the others had values of 2.4 mmol/l or less. We consider CSF lactate to be the best predictor in the clinical decision to institute antibiotic treatment of children with suspected bacterial meningitis.     

Cerebrospinal fluid lactic acid dehydrogenase activity. Levels in untreated and partially antibiotic-treated meningitis.

High levels of cerebrospinal fluid (CSF) lactic acid dehydrogenase (LDH) activity were found in 23 cases of bacterial meningitis, but significantly lower levels of CSF LDH activity were observed in 11 patients with viral meningitis and in 13 patients with no central nervous system infection. No correlation was found between levels of CSF LDH activity and specific agents or the amounts of CSF white blood cell, protein, and glucose. The number of meningitis cases of unknown cause that could be classified as probably bacterial or viral was increased by determination of the level of CSF LDH activity. The level of CSH LDH activity is useful in differentiating bacterial from viral meningitis and, along with determination of the CSF blood cell counts and protein and glucose levels, aids in classification of meningitis before culture results are available.     

The diagnostic and predictive value of cerebrospinal fluid lactate in children with meningitis. Its relation to current diagnostic methods

One hundred and thirty-three children with suspected meningitis aged from 11 days to 16 years were investigated with routine cerebrospinal fluid (CSF) laboratory methods: microscopy of a Gram-stained smear, bacterial culture, determination of leukocytes, lactate, and the CSF/blood glucose ratio. On the basis of bacterial cultures and clinical course, the children were classified into three groups: bacterial meningitis (n = 18), aseptic meningitis (n = 28), and a control group (n = 87). The main intention was to study the relation between current diagnostic methods and lactate. CSF lactate levels and cell counts, related significantly (p less than 0.01) better to the presence of bacterial meningitis than CSF/blood glucose ratios. Lactate levels exceed 2.4 mmol/l in all children with bacterial meningitis, but in none of the control group. Of 28 children with aseptic meningitis 3 had lactate in the range 2.5-2.7 mmol/l, while the others had values of 2.4 mmol/l or less. We consider CSF lactate to be the best predictor in the clinical decision to institute antibiotic treatment of children with suspected bacterial meningitis.     

Evaluation of polymerase chain reaction (PCR) for diagnosing Haemophilus influenzae b meningitis

A polymerase chain reaction (PCR) for detecting Hib in cerebrospinal fluid (CSF) was evaluated and compared with culture and a latex agglutination test (LAT) in a hospital-based prospective surveillance. We studied 107 children aged from 1 month to 12 years with a clinical and CSF profile suggestive of acute bacterial meningitis. CSF culture was performed on blood-chocolate agar by standard technique, LAT by a commercially available kit (Wellcogen) and PCR using total DNA extracted from CSF samples. Of 107 children, 79% had received one or more doses of injectable antibiotics. Hib was detected by culture in 14 cases, by LAT in 23 and by PCR in 37. All CSF samples that reveal Hib by culture or LAT had a PCR positive for Hib (sensitivity 100%). PCR also detected 14 additional cases of Hib meningitis which were not detected by culture or LAT. We conclude that PCR is a sensitive and specific diagnostic tool that may be valuable in a population with high pre-hospital antibiotic usage.     

山东地区肠道病毒中枢神经系统感染187例分析

目的 探讨山东地区中枢神经系统肠道病毒（EV）感染的实验和临床特点。方法 采用逆转录聚合酶链反应（RT-PCR）和病毒培养技术,检测187例无菌性脑膜炎患儿中,CSF中RT-PCR和病毒培养同时阳性者62例（33.16%)。病毒培养阴性的125例中,RT-PCR阳性93例（74%）;此93例中,4例同时在血清或尿分离到EV,本实验中,RT-PCR检测EV脑膜炎的阳性率为82.89%（155/187）,而病毒培养的阳性率为33.16%(62/187)。包括EV RNA的提取,RT-PCR的全部过程在4小时内可以完成,而病毒培养繁杂,平均需要4.6天得出结果。肠道病毒脑膜炎可以散发或局部暴发,临床特点在各个年龄组有所不同,5岁以内者以发热,呕吐,激惹多见,5岁以上者以头痛,畏光,疲劳,肌痛多见。结论 EV是山东地区无菌性脑膜炎最常见的病原体。临床症状一般较轻,无特异性;RT-PCR检测能快速,敏感的诊断EV感染,快速确诊可减少抗生素的应用和住院天数,有较高的社会效益和经济效益。     

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.     

小儿化脓性脑膜炎临床和病因学分析

目的探讨化脓性脑膜炎的病因,为诊治提供科学依据。方法收集住院化脓性脑膜炎患儿371例,男252例,女119例;平均年龄(2.67±3.32)岁。对患儿临床表现及血液和脑脊液(CSF)相关参数进行分析。结果 371例中≤1岁患儿占46.36%,<3岁占80.59%,以发热(90.29%)、抽搐(52.56%)等症状就诊。82.21%患儿白细胞计数(WBC)>10×109/L,74.42%患儿中性粒细胞比率>50%,85.44%患儿脑脊液WBC≥500×106/L。血培养革兰染色阳性(GSP)37例,革兰阳性菌(GPB)24例,革兰阴性菌(GNB)13例。脑脊液培养阳性34例,GPB 19例,GNB 15例。脑脊液检测出肺炎链球菌8例,流感嗜血杆菌3例,奈瑟菌1例。死亡7例(1.88%)中,脑脊液2例GNB阳性,5例化脓性/混浊,4例蛋白>150 mg/dl和葡萄糖<1 mg/dl。结论化脓性脑膜炎的发病年龄多在婴幼儿阶段,临床表现多种多样,血液和脑脊液相关参数分析,能较好的提供病因诊断依据,并为临床治疗及预后提供参考。     

Comparison of cerebrospinal fluid in newborns and in infants ≤2 months old with or without meningitis

Background: The aim of the present study was to evaluate the characteristics and accuracy of cerebrospinal fluid (CSF) parameters for neonatal meningitis, by comparing CSF data in newborns and in infants ≤2 months of age, with or without meningitis. Methods: This case–control study was performed on 120 newborns and infants ≤2 months old. 60 patients with meningitis were considered as the case group and 60 ill patients without meningitis were defined as the control group. Each of the two groups was divided into 0–1 months and 1–2 months old. CSF characteristics were compared in newborns in the case and control groups; in infants ≤2 months old in the case and control groups; and in healthy newborns and healthy infants ≤2 months old. Results: The mortality rate was 16.7% in the case group. The differences of CSF parameters in the case and control groups were mostly not significant, except for CSF glucose only in term newborns <7 days old (P= 0.04), and white cell count (WBC) only in 0–7‐day‐old term and preterm neonates (P= 0.04 and P= 0.01, respectively). Polymorphonuclear leukocyte (PMNL) level in the case group was significantly higher than in the control group (P= 0.02). CSF characteristics in healthy newborns were nearly the same as in healthy infants ≤2 months old. Prevalence of positive CSF culture was 31.7% in the case group. The most common pathogen was Neisseria meningitidis in the two age groups. The concomitant positive blood culture in the case group was 26.3%. Conclusion: In the case of meningitis with negative CSF culture and Gram stain, diagnosis can be made on CSF parameters, clinical and laboratory findings and suspicion of meningitis. Therefore, a clinical prediction rule to classify risk for bacterial meningitis on evaluation of CSF parameters in any region should be established. More regional trials are needed to enhance the probability of diagnosis according to CSF parameters.     

A Clinicl Picture of Aseptic Meningitis as Portrayed from a Study of 150 Patients During Three-Year Observation

One-hundred and fifty patients with aseptic meningitis were studied in order to investigate their clinical manifestations and cerebrospinal fluid (CSF) contents. The patients were classified according to causative organisms and/or associated diseases. Hypoglychorrhachia was found in nearly half of the total CSF samples from patients with mumps meningitis. A coxsackie virus was isolated from a CSF specimen from one patient who had typical meningeal signs but had no pleocytosis (so-called meningism).     

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.     

Rapid diagnosis of bacterial meningitis in children with fluorescence quantitative polymerase chain reaction amplification in the bacterial 16S rRNA gene

Polymerase chain reaction (PCR) techniques have been increasingly used to detect microbial DNA in cerebrospinal fluid (CSF) for the diagnosis of bacterial meningitis. In order to determine the rapidity, sensitivity and specificity of 16S rRNA-based fluorescence quantitative polymerase chain reaction (FQ-PCR), 16S rRNA-based FQ-PCR, CSF bacterial culture and CSF routine analysis were compared in the diagnosis of bacterial meningitis in children. Twenty children who were clinically suspected of bacterial meningitis were included in this study. A total of 2.0 ml of CSF was collected from every child and was subjected to 16S rRNA-based FQ-PCR, CSF culture and CSF routine analysis. Bacterial DNA copies and the cycle threshold (CT) value of the 16S rRNA-based FQ-PCR was recorded, and the results were compared with CSF culture and CSF routine analysis. Seven children were found to be positive with a rate of 35% (7/20) when detected with 16S rRNA-based FQ-PCR and four children displayed a positive rate of 20% (4/20) with the CSF culture method. These two groups displayed a significant difference, with a p-value of 0.002. The method of 16S rRNA-based FQ-PCR demonstrated a high specificity when compared to the standard microbes. A negative correlation was noted between the CT value and the bacteria DNA copies, and the CT value was indicative of the seriousness of bacterial meningitis. 16S rRNA-based FQ-PCR was proved to be a more rapid, sensitive and specific method compared with CSF culture and it should have promising usage in the diagnosis of bacterial meningitis.     

Bacteroides fragilis concealed in an infant with Escherichia coli meningitis

Anaerobic meningitis in infants is rare, therefore a high index of clinical suspicion is essential as routine methods for processing cerebrospinal fluid (CSF) do not detect anaerobes and specific antimicrobial therapy is required. We present an infant with Escherichia coli meningitis where treatment‐resistance developed in association with culture negative purulent CSF. These features should have alerted us to the presence of anaerobes, prompting a search for the causes of polymicrobial meningitis in infants.     

A hospital outbreak of aseptic meningitis due to echovirus type 30 in Antalya,Turkey

We analyzed clinical and laboratory findings of 23 hospitalized patients with aseptic meningitis in the Department of Pediatrics, Akdeniz University Hospital. The patients presented with the classic symptoms and signs of aseptic meningitis. Protein levels of the cerebrospinal fluid (CSF) samples ranged from 18 to 99 mg/dl, with a mean of 36.5 +/- 4.9 mg/dl. The mean ratio of CSF glucose compared to blood samples was 0.73. Echovirus type 30 was identified in CSF and/or stool samples of 19 patients. Four patients had negative virus culture. The outcome was favorable in all patients. We thought that this outbreak of aseptic meningitis in our department might denote a summer outbreak in the city. However, this remained unproven since field investigations could not be completed. Advances in virus culture or polymerase chain reaction techniques and satisfactory medical records may help patient care by promoting early diagnosis and by eliminating unnecessary antibiotic therapy, allowing epidemiological studies.     

Haemophilus influenzae type b still remains a leading cause of meningitis among unvaccinated children--a prospective CSF analysis study

A prospective, hospital-based cerebrospinal fluid (CSF) analysis study was undertaken in 65 children who had diagnostic lumbar puncture on admission for suspected central nervous system infections. Twenty-three children were clinically diagnosed to have had sepsis and/or meningitis. CSF bacterial culture grew Haemophilus influenzae type b (Hib) in four cases and Streptococcus pneumonia (SP) was cultured in another child. Bacterial antigen was detected in 13 other CSF specimens and the pathogens were Hib (n = 9), SP (n = 3) and Group B Streptococcus (n = 1). No etiologic cause was identified to explain the abnormal CSF pleocytosis and biochemistry in the remaining five cases. In contrast, the CSF analysis was normal in 42 other children with probable viral and non-infectious neurological condition, mostly febrile convulsions. The overall frequency rate for all types of meningitis and especially for Hib meningitis were 43 and 31 cases per 100,000 children < 5 years of age, respectively. These findings support our earlier observations that Hib meningitis still remains the leading cause of childhood meningitis in our region. Also it reaffirms the observation that bacterial meningitis may often be under-reported if CSF positive culture alone is considered for the diagnosis.     

Pneumococcal meningitis in the newborn period in a prevaccination era: a 10-year experience at a tertiary intensive care unit

There are few data with respect to pneumococcal meningitis in neonates. Epidemiological aspects, clinical features and outcomes in newborn infants diagnosed with pneumococcal meningitis were evaluated in this study. Nineteen newborn infants in a neonatal intensive care unit diagnosed with culture-proven community-acquired bacterial meningitis between January 1999 and December 2008 were reviewed, and of them, eight patients were diagnosed as pneumococcal meningitis. Overall, among 10,186 hospitalized newborn infants, 132 community-acquired sepsis/meningitis cases (1.3%) were suspected, and blood cultures were performed in all, while cerebrospinal fluid (CSF) cultures could be performed in 124 cases. Rate of blood culture positivity was 45%. Nineteen (15.3%) of 124 were diagnosed as culture-proven community-acquired bacterial meningitis, which was confirmed by CSF growth. Eight (42.1%) of 19 had pneumococcal meningitis. In pneumococcal cases, abundant Gram-positive diplococci were seen on CSF smear and Streptococcus pneumoniae was isolated from CSF cultures. All isolates were susceptible to penicillin and third-generation cephalosporins. Irritability (n: 7), poor sucking (n: 7) and fever (n: 6) were the principal findings on the initial physical examination. Of all patients with pneumococcal meningitis, four were initially given cefotaxime plus amikacin treatment, and the remaining four were initially given cefotaxime plus ampicillin plus vancomycin. Antibiotic treatment in two patients was revised during their clinical course. Additionally, in three patients, vancomycin and ampicillin was discontinued on the third day when antibiogram of CSF cultures revealed penicillin sensitivity. Overall, mortality in pneumococcal meningitis was 50%. In the surviving patients, two had epilepsy, one sensorineural hearing loss, and two mental-motor retardation. Pneumococcal meningitis was the leading cause of community-acquired neonatal meningitis in our patients. Immunization against pneumococcal disease in developing countries would be beneficial for public health and for newborn infants.     

足月儿与早产儿细菌性脑膜炎的临床分析

目的 探讨足月儿和早产儿细菌性脑膜炎的临床特征及转归特点。方法 回顾性分析102例新生儿细菌性脑膜炎患儿的临床资料,根据胎龄分为早产儿组（n=46）及足月儿组（n=56）,比较两组患儿临床表现、实验室结果、影像学结果及临床转归。结果 早产儿组临床表现主要为反应差和呼吸暂停/急促（P < 0.05）,足月儿组则以发热及抽搐多见（P < 0.05）。足月儿组脑脊液糖高于早产儿组（P < 0.05）,早产儿组C-反应蛋白、血培养阳性率及不良预后发生率高于足月儿组（P < 0.05）。两组外周血白细胞计数、脑脊液白细胞、脑脊液蛋白及脑脊液培养阳性率差异无统计学意义（P > 0.05）。结论 早产儿及足月儿细菌性脑膜炎临床表现有所不同,早产儿组不良预后发生率更高。     

Peripheral Facial Palsy in Children: A Cerebrospinal Fluid Study

Seven children and five adults with acute, peripheral facial palsy were investigated by clinical, blood and cerebrospinal fluid (CSF) examinations. Routine blood examinations and blood and CSF serological tests were normal. In all children studied the CSF showed an increased number of mononuclear white cells despite the absence of clinical signs of meningitis in all but one. Two of the twelve patients studied had normal CSF. Contrary to that in adults the outcome in children was excellent, all recovered totally within three months. The present study indicates that acute, peripheral facial palsy is a manifestation of a generalized disorder with subclinical pathology of the central nervous system, and that in children a lumbar puncture should be done, even if there are no signs of meningitis.