Outpatient management of children at low risk for bacterial meningitis.

OBJECTIVE: To determine the outcome of children aged 2-14 years with cerebrospinal fluid (CSF) pleocytosis and at very low risk for bacterial meningitis managed as outpatients without antibiotics. METHODS: Multicentre, prospective, observational study conducted at nine Spanish paediatric EDs. Patients were diagnosed with meningitis based on clinical suspicion of meningitis and CSF pleocytosis when evaluated in the ED. Children between 2 and 14 years of age with pleocytosis and very low-risk criteria for bacterial meningitis (well appearing, Bacterial Meningitis Score (BMS)=0, procalcitonin (PCT)<0.5 ng/mL and observation without deterioration for less than 24 hours in the ED) were treated as outpatients without antibiotics pending CSF cultures. The primary composite outcome was a final diagnosis of bacterial meningitis or return to the ED for clinical deterioration. RESULTS: Of 182 children between 2 and 14 years old diagnosed with meningitis, 56 met the very low-risk criteria and 45 were managed as outpatients. None was diagnosed with bacterial meningitis or returned due to clinical deterioration. Another 31 patients with BMS=1 (due to a peripheral absolute neutrophil count (ANC)>10 000/mm3) and PCT <0.5 ng/mL were managed as outpatients, diagnosed with aseptic meningitis and did well. BMS using PCT had the same sensitivity but greater specificity than classic BMS. CONCLUSIONS: This set of low-risk criteria appears safe for the outpatient management without antibiotics of children with CSF pleocytosis. Larger studies are needed to evaluate the predictive values of replacing peripheral ANC with PCT in the BMS.

Vaccine preventable meningitis in Malaysia: epidemiology and management.

Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9-25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis.

Overview of post-infective hydrocephalus.

INTRODUCTION: Post-infective hydrocephalus refers to accumulation of fluid within the cranial cavity (hydrocephalus) secondary to either pyogenic or tuberculous meningitis. Whereas in the former condition, fibrous adhesions develop in the ventricles and arachnoid villi, in the latter, the fibrosis is mainly basal. METHODS: This is a review of the author's personal series as well as published literature on post-infective hydrocephalus. CONCLUSION: The aim of treatment in hydrocephalus following pyogenic meningitis is to sterilize the cerebrospinal fluid (CSF) and then to drain the ventricles after conversion of a multiloculated cavity into a single cavity. In hydrocephalus associated with tuberculous meningitis, CSF diversion is not always necessary and should be reserved for cases where clinical deterioration occurs pari passu with increase in ventricular size and intraventricular pressure.

Cerebrospinal fluid lactate dehydrogenase isoenzymes in children with bacterial and aseptic meningitis.

Differentiation of bacterial from aseptic meningitis may be difficult. Our aim was to determine the pattern of distribution of lactate dehydrogenase (LDH) isoenzymes in the cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis. One hundred and fifty-seven patients with suspected meningitis were enrolled in the study. They were divided into 3 groups according to the culture- or bacterial antigen assay-proven diagnosis and CSF findings: bacterial meningitis (n = 31), aseptic meningitis (n = 65), and non-meningitis (n = 61). Total LDH level and percentages of LDH isoenzymes in the CSF were measured in each patient. Each group showed a distinct LDH isoenzyme distribution pattern, with a statistically significant difference among the groups in the percentages of the various isoenzymes. Compared with the non-meningitis group, total LDH activity in the CSF was high in the aseptic meningitis group (49.82+/-35.59 U/L, P < 0.001) and exaggerated in the bacterial meningitis group (944.53+/-112.3 U/L, P < 0.001). Low LDH-2 levels were unique to bacterial meningitis (P < 0.01), whereas high LDH-3 levels were characteristic of aseptic meningitis (P < 0.05). Both groups had low levels of LDH-1 and high levels of LDH-4 and LDH-5. In conclusion, the LDH isoenzyme pattern may be of clinical diagnostic value in meningitis, particularly when culture results are pending.

Rapid etiological classification of meningitis by NMR spectroscopy based on metabolite profiles and host response.

Bacterial meningitis is an acute disease with high mortality that is reduced by early treatment. Identification of the causative microorganism by culture is sensitive but slow. Large volumes of cerebrospinal fluid (CSF) are required to maximise sensitivity and establish a provisional diagnosis. We have utilised nuclear magnetic resonance (NMR) spectroscopy to rapidly characterise the biochemical profile of CSF from normal rats and animals with pneumococcal or cryptococcal meningitis. Use of a miniaturised capillary NMR system overcame limitations caused by small CSF volumes and low metabolite concentrations. The analysis of the complex NMR spectroscopic data by a supervised statistical classification strategy included major, minor and unidentified metabolites. Reproducible spectral profiles were generated within less than three minutes, and revealed differences in the relative amounts of glucose, lactate, citrate, amino acid residues, acetate and polyols in the three groups. Contributions from microbial metabolism and inflammatory cells were evident. The computerised statistical classification strategy is based on both major metabolites and minor, partially unidentified metabolites. This data analysis proved highly specific for diagnosis (100% specificity in the final validation set), provided those with visible blood contamination were excluded from analysis; 6-8% of samples were classified as indeterminate. This proof of principle study suggests that a rapid etiologic diagnosis of meningitis is possible without prior culture. The method can be fully automated and avoids delays due to processing and selective identification of specific pathogens that are inherent in DNA-based techniques.

A decision rule for predicting bacterial meningitis in children with cerebrospinal fluid pleocytosis when gram stain is negative or unavailable.

OBJECTIVES: Among children with cerebrospinal fluid (CSF) pleocytosis, the task of separating aseptic from bacterial meningitis is hampered when the CSF Gram stain result is unavailable, delayed, or negative. In this study, the authors derive and validate a clinical decision rule for use in this setting. METHODS: This was a review of peripheral blood and CSF test results from 78 children (< 19 years) presenting to Children's Hospital Columbus from 1998 to 2002. For those with a CSF leukocyte count of > 7/microL, a rule was created for separating bacterial from viral meningitis that was based on routine laboratory tests, but excluded Gram stain. The rule was validated in 158 subjects seen at the same site (Columbus, 2002-2004) and in 871 subjects selected from a separate site (Boston, 1993-1999). RESULTS: One point each (maximum, 6 points) was assigned for leukocytes > 597/microL, neutrophils > 74%, glucose < 38 mg/dL, and protein > 97 mg/dL in CSF and for leukocytes > 17,000/mL and bands to neutrophils > 11% in peripheral blood. Areas under receiver-operator-characteristic curves (AROCs) for the resultant score were 0.98 for the derivation set and 0.90 and 0.97, respectively, for validation sets from Columbus and Boston. Sensitivity and specificity pairs for the Boston data set were 100 and 44%, respectively, at a score of 0 and 97 and 81% at a score of 1. Likelihood ratios (LRs) increased from 0 at a score of 0 to 40 at a score of > or = 4. CONCLUSIONS: Among children with CSF pleocytosis, a prediction score based on common tests of CSF and peripheral blood and intended for children with unavailable, negative, or delayed CSF Gram stain results has value for diagnosing bacterial meningitis.

Changing epidemiology of adult bacterial meningitis in southern taiwan: a hospital-based study.

BACKGROUND: Many factors may influence the epidemiologic trend of adult bacterial meningitis (ABM). The objective of this study was to analyze recent epidemiologic trends of ABM in order to provide a better therapeutic strategy. MATERIALS AND METHODS: The clinical features, laboratory data, and therapeutic outcomes of 181 ABM cases collected in the last 6.5 years (July 1999-December 2005) were analyzed. The results were compared with those of our previous study (202 cases, January 1986-June 1999). RESULTS: The 181 cases consisted of 130 men (age range: 18-82 years) and 51 women (age range: 18-78 years). Monomicrobial infection and mixed infection were found in 165 cases and 16 cases, respectively. A preceding postneurosurgical state was noted in 56.9% (103/181) of cases. Despite a decrease in incidence, Klebsiella pneumoniae (25.5%, 42/165) was still the most common pathogen. A marked increase of Acinetobacter meningitis (11.5%, 19/165) was noted, which replaced Pseudomonas meningitis as the second most common Gram-negative pathogen in ABM. A marked increase in staphylococcal infection, accounting for 23% (38/165) of all cases, was also noted, of which 76% (29/38) were methicillin-resistant strains. The therapeutic result showed a mortality rate of 30.3% (55/181). Significant prognostic factors included septic shock and age at infection. CONCLUSIONS: This study revealed a change in the epidemiologic trend of ABM, with an increase in the number of patients with a postneurosurgical state and a rising incidence of Acinetobacter and staphylococcal infections. Clinicians should pay greater attention to these changes, which may affect their management of ABM.

Predictors of long term neurological outcome in bacterial meningitis.

OBJECTIVE: To study the long-term neurological and developmental outcome and the clinical and laboratory predictors of sequelae in children with acute bacterial meningitis (ABM). METHODS: Detailed clinical and demographic data was retrieved from the medical records of study children. Subsequently they were followed up for a minimum of 12 months after discharge for development, neurological and hearing assessment. All sequelae were identified and divided into minor or major. For analysis data was divided into 2 groups those with sequelae and without sequelae at follow-up. Statistical analysis was done using SPSS version 10.00 and Epi Info version 2000. RESULTS: 61 boys and 19 girls, a mean age of 31.4 +/= 41.9 months at the time of ABM, were included in the study. Of these 62.5% children were infants. Mean age at follow-up was 58.6 +/= 47.2 months. Sequelae were observed in 32 (40%) children (8 (10%) minor and 24 (30%) major). Mean social quotient at follow-up was 92.8 +/= 32.6. Developmentally 22 (37.9%) children were normal and 20 (34.5%) had global delay. Seizures (P=0.015), cranial nerve palsy (P=0.0065), abnormal deep tendon reflexes (P=0.002), Glasgow coma scale score (GCS) < 8 (P = 0.044) at admission, a CSF culture positive for bacteria and abnormal findings on ultrasonography or computed tomography of head at admission had significant association with sequelae at follow-up. All children (7/7) who had infarct on CT scan (P=0.001) and 12 (80%) of 15 patients who had hydrocephalus (OR - 9.0, 95% CI - 2.03-45.6, P=0.001) diagnosed on CT scan developed severe sequelae. On multiple regressions GCS score <8, presence of cranial nerve palsy and abnormal deep tendon reflexes were independent predictors of sequelae. CONCLUSION: Neurological and audiological sequelae and global developmental delay may be seen in about one third of survivors of bacterial meningitis. GCS score <8, presence of infarct or cranial nerve palsy, or hydrocephalous on CT/ ultrasound at admission may help in identification of children most likely to need long term follow up and rehabilitation.

Sepsis y meningitis neumocócica 2001-2003: incidencia, clínica e identificación de serotipos / Pneumococcal sepsis and meningitis, 2001-2003: incidence, clinical features and identification of serotypes

Objetivo: Determinar las tasas de incidencia, características clínicas y serotipos causantes de meningitis y sepsis neumocócica en los últimos años. Material y métodos: Estudio prospectivo de los casos de sepsis y meningitis neumocócica que ingresaron en nuestro hospital entre enero de 2001 y febrero de 2003. Se aisló el germen en cultivo de líquido cefalorraquídeo y/o sangre. Se identificó el serotipo de neumococo en los casos que se produjeron en 2002 y 2003. Se analizan los parámetros epidemiológicos, bacteriológicos y clínicos. Resultados: Se han diagnosticado 14 casos, en 12 niños; dos niños presentaron 2 episodios de meningitis y/o sepsis. La incidencia anual fue de 15,38 casos por cada 100.000 niños menores de 2 años y de 9,16 casos por cada 100.000 niños menores de 5 años de edad. El 67% eran menores de 2 años de edad. Todos los mayores de 2 años presentaban algún factor de riesgo de padecer enfermedad neumocócica invasora. Los serotipos identificados fueron: 6B en cinco casos, 14 en dos y 18C en uno. El 69% de las cepas aisladas presentaba sensibilidad intermedia o resistencia a penicilina y el 54% mostraba resistencia a eritromicina. El 57% de los niños sufrieron complicaciones graves: dos (14%) quedaron con secuelas neurológicas graves y 3 fallecieron (21 %).Conclusiones: Las sepsis y meningitis neumocócicas tienen una alta morbimortalidad. En el último año, hemos observado un aumento importante de su incidencia. Todos los serotipos identificados están incluidos en la vacuna conjugada heptavalente. Actualmente, el método más eficaz para prevenir esta grave enfermedad es el uso generalizado de la vacuna heptavalente

Objective. To determine the incidence, clinical features and serotypes implicated in pneumococcal sepsis and meningitis in recent years. Material and methods. We performed a prospective study of cases of pneumococcal sepsis and meningitis that occurred in our hospital between January, 2001 and February, 2003. Streptococcus pneumoniae was isolated from cerebrospinal fluid and/or blood cultures in all the patients. Serotyping was performed in the cases occurring in 2002 and 2003. The epidemiological, bacteriological and clinical characteristics were studied. Results. Fourteen cases were identified in 12 patients. Two children had recurrent meningitis and/or sepsis. From 0 to 2 years of age, the incidence of pneumococcal meningitis was 15.38 cases per 100,000 population per year, and from 0 to 5 years of age, it was 9.16 cases per 100,000 population per year. Eight patients (67%) were aged less than 2 years. All children older than 2 years had a predisposing disease. The most common serotype was 6B (5 cases). Penicillin-resistant strains were detected in 69% of cases and erythromycin-resistant strains in 54%. Fifty-seven percent of the children developed serious complications. Conclusions. Pneumococcal meningitis and sepsis are common causes of morbidity and mortality. Their incidence increased considerably over the past year. All the serotypes isolated were included in the heptavalent conjugate vaccine. The most effective way to combat these severe infections would be through widespread vaccination with the conjugate pneumococcal vaccine

[Humoral and cellular immunity in meningitis of various etiology]. / Gumoral'nyi i kletochnyi immunitet pri meningitakh razlichnoi étiologii.

The parameters of humoral and cellular immunity were studied in patients with meningitis due to tuberculosis and other diseases. Peripheral blood and spinal fluid were measured in 91 and 76 patients with tuberculous meningitis, in 75 and 59 with purulent meningitis, and in 54 and 33 with serous meningitis, respectively. Comparing assessment of the findings revealed profound changes in the content of T lymphocytes and their subpopulations. With this, impaired cellular immunity appeared not only as changes in the relative count of immuno-complement cells, but in their different functional activity detectable by blast cell formation. Thus, in tuberculous meningitis, 18.11 +/- 0.95% of peripheral lymphocytes and 15.1 +/- 1.2% spinal fluid were exposed to the specific blast cell transformation antigen PPD whereas they were 1.94 +/- 0.3 and 2.4 +/- 0.9% (p < 0.001) and 1.86 +/- 0.28 and 3.1 +/- 0.8% (p < 0.001), respectively. Elevated spinal fluid levels of beta 2-microglobulin and IgE in patients are shown to be a differential diagnostic sign typical of tuberculous meningitis.

Use of oligoprobes on amplified DNA in the diagnosis of bacterial meningitis.

An approach based on the 16 S rDNA polymerase chain reaction (16S PCR) and oligoprobe hybridization was applied to 77 cerebrospinal fluid samples submitted to the clinical microbiology laboratory for culture. Broad-range 16S rDNA primers were selected in conserved regions of the gene. Oligoprobes specific for Neisseria meningitidis, Haemophilus influenzae, Streptococcus spp., and Mycobacterium tuberculosis were selected in specific variable regions of the amplified 600 base pairs (bp) in the 16S rDNA. None of the oligoprobes cross hybridized with DNA from the other bacteria or from common contaminants. There were no false-negative results in culture-positive cerebrospinal fluid samples. Ten cases of meningitis caused by bacteria other than the four probes were not identified by any of the four probes. In culture-negative cerebrospinal fluid samples with some abnormal chemical parameters, there were 14 amplicons -- one of Haemophilus influenzae, three of Streptococcus spp., six of Mycobacterium tuberculosis, and four not identified -- while in normal cerebrospinal fluid samples there were no amplicons.

[Evaluation of prognosis in purulent meningitis-myelitis based on the Glasgow Coma Scale]. / Ocena rokowania w ropnych zapaleniach opon mózgowo-rdzeniowych na podstawie Skali Spiaczki Glasgow.

We presented data from the investigation of the usefulness of the Glasgow Coma Scale in predicting the outcome of bacterial meningitis. Patients who aggregated high Glasgow Coma Scale scores had a good prognosis, whereas those patients with low scores had a very poor prognosis, inspite of this limitation the Glasgow Coma Scale seems to be a valuable supplement to the physical examination of patients with bacterial meningitis and may help in predicting the outcome of the disease.

Operative sepsis in neurosurgery: a method of classifying surgical cases.

Neurosurgical operations have traditionally been classified along the lines of general surgical procedures. A prospective study, during an 18-month period, was undertaken in 2249 patients undergoing neurosurgical procedures to establish and evaluate a method of classifying surgical cases by the use of specific neurosurgical criteria. Patients were placed in one of five categories according to the level and type of contamination at the time of surgery. Infection included all abnormal wounds and was documented as deep when infection occurred beneath the galea (subgaleal pus, osteitis, abscess/empyema, ventriculomeningitis) and as superficial if only the scalp (including wound erythema) was involved. A statistically significant difference in the sepsis rate was found in the different categories (P < 0.0001). Of the 342 "dirty cases," 9.1% of patients developed further wound sepsis. Concomitant cerebrospinal fluid fistulae (44%), second operations (11.8%), and patients with penetrating injuries (9.2%) were the major factors implicated in sepsis in the "contaminated" category (9.7%). In the "clean contaminated" category, a sepsis rate of 6.8% was found. Prolonged surgery (longer than 4 hours) was also implicated in higher infection rates (13.4%). This study strongly supports the separation of patients who have foreign materials implanted (sepsis rate = 6.0%) from "clean" patients, essentially cases categorized as having no known risk factors that may affect sepsis, in whom a sepsis rate of 0.8% was found (P < 0.001). Importantly, surgery for the repair of so-called "clean" neural tube defects in neonates requires separate consideration. An infection rate of 14.8% existed in this subgroup. A uniform system of reporting wound abnormalities is also proposed.

Classification of frontal fossa fractures associated with cerebrospinal fluid rhinorrhea, pneumocephalus or meningitis. Indications and time for surgical treatment.

The classification of anterior fossa fractures with their sequelae: cerebrospinal fluid (CSF) rhinorrhea, pneumocephalus, or meningitis is presented. This classification is based on five selection criteria which are discussed in this paper. This classification resulted in the table of indications for operative treatment, according to which the appropriate time for operation in urgent cases is immediately, in cases with absolute indication 5 to 6 days after the injury, in long-lasting CSF rhinorrhea or pneumocephalus 10 days after the onset, in intermittent or delayed rhinorrhea and/or pneumocephalus as soon as these signs occur, and in cases of meningitis soon after recovery. This study is based on the analysis of 52 consecutive surgically treated cases, collected from 1984 up to December 1989.

Meningitis bacteriana: bases racionales del tratamiento

La mortalidad por meningitis, cercana al 100 por ciento en la era pre-antibiótica, se ha reducido en la década de los años 80 a niveles de seis al 30 por ciento dependiendo de la edad, el agente etiológico y el lugar de estudio. Este descenso se debe al desarrollo de antimicrobianos con adecuada difusión y concentración en el líquido cefalorraquídeo (LCR), sumando al desarrollo de técnicas de diagnóstico rápido. La morbilidad y las secuelas, al contrario, no se han modificado, persistiendo entre 20 y 50 por ciento, debido a la limitación que el tratamiento adecuado ejerce sobre los eventos fisiopatológicos inflamatorios responsables de la evolución y las secuelas. La búsqueda de las estrategias para reducir estos efectos adversos, es el marco conceptual que ha predominado en la investigación de meningitis en los últimos años, buscando definir claramente los eventos fisiopatológicos e investigando su posible control que, junto con la evaluación de nuevos regímenes antibióticos, deben aclarar el futuro de las secuelas secundarias a meningitis bacteriana.