FilmArray Meningitis/Encephalitis (ME) panel in the diagnosis of bacterial meningitis

ABSTRACT The precise diagnosis of bacterial meningitis is essential. Cytological and biochemical examination of cerebrospinal fluid (CSF) are not specific. Conventional methods for bacterial meningitis lack sensitivity or take too long for a final result. Therefore, other methods for rapid and accurate diagnosis of central nervous system infections are required. FilmArray meningitis/encephalitis (ME) panel is a PCR multiplex for simultaneous and rapid identification of 14 pathogens, including 6 bacteria, 7 viruses, and Cryptococcus. We evaluated 436 CSF samples submitted to FilmArray ME Panel. Among them, 25 cases were positive for bacteria, being Streptococcus pneumonia the most frequent (48 %). Among positive cases for bacteria, 60 % were positive only with FilmArray. All the bacterial meningitis cases in which the only positive test was FilmArray had CSF findings suggestive of bacterial meningitis, including neutrophilic pleocytosis, increased CSF protein and lactate, and decreased CSF glucose. These findings suggest that FilmArray may increase the diagnostic sensitivity for bacterial meningitis.

Comparison of cerebrospinal fluid lactate with physical, cytological, and other biochemical characteristics as prognostic factors in acute bacterial meningitis / Comparação do lactato no líquido cefalorraquidiano com as características físicas, citológicas e outros marcadores bioquímicos, como fator prognostico nas meningites bacterianas agudas

ABSTRACT Bacterial meningitis (BM) is associated with a high morbidity and mortality. Cerebrospinal fluid (CSF) lactate may be used as a prognostic marker of this condition. We hypothesized that CSF lactate levels would remain elevated in participants who died of acute BM compared with those who recovered from this disease. Objective: To evaluate the potential use of lactate and other CSF biomarkers as prognostic markers of acute BM outcome. Methods: This retrospective, longitudinal study evaluated dynamic CSF biomarkers in 223 CSF samples from 49 patients who fulfilled the inclusion criteria of acute BM, with bacteria identified by CSF culturing. The participants were grouped according to outcome: death (n = 9; 18.37%) and survival (n = 40; 81.63%). All participants received appropriate antibiotic treatment. Results: In the logistic regression model, lactate concentration in the final CSF sample, xanthochromia, and CSF glucose variation between the first and last CSF samples were predictors of a poor outcome (death). In contrast, decrease in CSF white blood cell count and CSF percentage of neutrophils, increase in the percentage of lymphocytes, and normalization of the CSF lactate concentration in the last CSF sample were predictors of a good prognosis. Conclusion: The study confirmed the initial hypothesis. The longitudinal analysis of CSF lactate is an important predictor of prognosis in acute BM.

RESUMO As meningites bacterianas (MB) estão associadas à alta morbidade e mortalidade. O lactato no líquido cefalorraquidiano (LCR) pode ser usado como biomarcador de prognóstico nas MB. A hipótese desse estudo é que os níveis de lactato no LCR se mantém elevados entre pacientes com MB aguda que evoluem para óbito, ao contrário do que ocorre em pacientes com bom prognóstico. Objetivo: Avaliar o uso potencial do lactato e outros marcadores no LCR como indicador de prognóstico na MB aguda. Métodos: Foi realizado um estudo retrospectivo longitudinal da dinâmica dos biomarcadores bioquímicos, celulares e físicos no LCR. Foram analisadas 223 amostras de 49 pacientes com MB aguda com bactérias identificadas por cultura do LCR. Os participantes foram divididos em dois grupos de acordo com o desfecho: óbito (n = 9; 18,37%) e não óbito (n = 40; 81,63%). Todos os participantes receberam antibioticoterapia adequada. Resultados: No modelo de regressão logística, as variáveis que diferiram significativamente entre os dois grupos foram concentração de lactato na amostra final de LCR, xantocromia e variação da concentração de glicose entre a primeira e a última amostra de LCR. A alteração desses fatores indicou desfechos negativos (óbito), enquanto a diminuição do número de leucócitos e da porcentagem de neutrófilos, assim como a normalização da concentração de lactato no LCR foram preditores de bom prognóstico. Conclusão: O estudo confirmou a hipótese inicial. A análise longitudinal do lactato no LCR é um importante preditor de prognóstico na MB aguda.

Validation of multiplex PCR for the diagnosis of acute bacterial meningitis in culture negative cerebrospinal fluid / Validação do PCR multiplex para o diagnóstico de meningite bacteriana aguda com cultura de liquido cefalorraquidiano negativa

ABSTRACT This study evaluated the operational characteristics of the multiplex polymerase chain reaction (PCR) for cerebrospinal fluid (CSF) from patients with cellular and biochemical characteristics of acute bacterial meningitis and positive or negative CSF cultures. Methods: Multiplex PCR was performed for 36 CSF samples: culture-proven acute bacterial meningitis (n = 7), culture-negative acute bacterial meningitis (n = 17), lymphocytic meningitis (n = 8), and normal CSF (n = 4). The operational characteristics of multiplex PCR were evaluated with definite and probable bacterial meningitis, using culture positive, cytological and biochemical CSF characteristics as the gold standard. Results: Multiplex PCR for CSF was efficient in the group with CSF cellular and biochemical characteristics of acute bacterial meningitis but with a negative CSF culture. This group demonstrated high specificity, positive predictive value, and efficiency. Conclusions: Multiplex PCR for CSF can improve the speed and accuracy of acute bacterial meningitis diagnosis in a clinical setting as a complement to classical immunological and bacteriological assays in CSF. It is also useful for CSF culture-negative acute bacterial meningitis.

RESUMO Este estudo avaliou as características funcionais da reação em cadeia da polimerase (PCR) multiplex para amostras de líquido cefalorraquidiano (LCR) de pacientes com características celulares e bioquímicas de meningite bacteriana aguda e culturas de LCR positivas ou negativas. Métodos: O PCR multiplex foi realizado em 36 amostras de LCR: meningite bacteriana aguda comprovada por cultura (n = 7), meningite bacteriana aguda com cultura negativa (n = 17), meningite linfocítica (n = 8) e LCR normal (n = 4). As características funcionais do PCR multiplex foram avaliadas para meningite bacteriana definitiva e provável, utilizando cultura positiva, características citológicas e bioquímicas do LCR como padrão-ouro. Resultados: O PCR multiplex do LCR foi eficiente no grupo com características celulares e bioquímicas do LCR de meningite bacteriana, mas com cultura do LCR negativa. Este grupo demonstrou especificidade, valor preditivo positivo e eficiência altos. Conclusões: Os autores concluíram que o PCR multiplex do LCR pode melhorar a velocidade e a precisão do diagnóstico de meningite bacteriana em um ambiente clínico como complemento aos ensaios imunológicos e bacteriológicos clássicos no LCR. Também é útil para meningite bacteriana aguda com cultura de LCR negativa.

Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children / Lactato no líquido cefalorraquidiano: um marcador diferencial para meningite bacteriana e meningite viral em crianças

Abstract Objective: To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. Methods: Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. Results: At a cut-off value of 3 mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. Conclusions: The authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3 mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2 mmol/L.

Resumo Objetivo: Estudar o desempenho do lactato no líquido cefalorraquidiano como biomarcador para diferenciar a meningite bacteriana da meningite viral em crianças, e definir uma concentração de lactato ótima no líquido cefalorraquidiano que possa ser significativa para a diferenciação. Métodos: Foram estudadas crianças com achados clínicos compatíveis com meningite. O nível de lactato no líquido cefalorraquidiano e outros parâmetros convencionais do líquido cefalorraquidiano foram registrados. Resultados: Em um valor de corte de 3 mmol/L, o lactato no líquido cefalorraquidiano apresentou uma sensibilidade de 0,90, especificidade de 1,0, valor preditivo positivo de 1,0, valor preditivo negativo de 0,963, com uma precisão de 0,972. Os índices de probabilidade positivo e negativo foram 23,6 e 0,1, respectivamente. Para comparação entre a meningite bacteriana e viral, a área abaixo da curva do lactato no líquido cefalorraquidiano foi 0,979. Conclusões: Concluímos que o lactato no líquido cefalorraquidiano possui alta sensibilidade e especificidade na diferenciação da meningite bacteriana da meningite viral. Embora em um valor de corte de 3 mmol/L o lactato no líquido cefalorraquidiano possua alta precisão de diagnóstico da meningite bacteriana, os níveis médios na meningite viral permanecem basicamente abaixo de 2 mmol/L.

Accuracy of heparin binding protein: as a new marker in prediction of acute bacterial meningitis

ABSTRACT Background: Cerebrospinal fluid bacterial culture is the gold-standard for confirmation of acute bacterial meningitis, but many cases are not culture confirmed. Antibiotics reduce the chance of a microbiological diagnosis. Objective to evaluate efficacy of Heparin-binding protein in diagnosis of bacterial meningitis. Patients: 30 patients diagnosed with acute bacterial meningitis, 30 viral meningitis, and 30 subjects with normal CSF findings. Design: Diagnosis was based on history, clinical criteria, CSF examination, latex agglutination & culture, and sensitivities and response to therapy. HBP was measured using enzyme-linked immunosorbent technique in both serum & CSF. Results: Cerebrospinal fluid HBP levels averaged 0.82 ± 0.3 ng/mL in controls, 3.3 ± 1.7 ng/mL in viral and 174.8 ± 46.7 ng/mL in bacterial meningitis. Mean serum level was 0.84 ± 0.3 ng/mL in the controls, 3.7 ± 1.9 ng/mL in viral, and 192.2 ± 56.6 ng/mL in bacterial meningitis. Both HBP levels were significantly higher in patients with bacterial meningitis. Cut-offs of 56.7 ng/ml and 45.3 ng/ml in cerebrospinal fluid & serum showed 100% overall accuracy. Even in patients who received prior antibiotics, remained elevated. Conclusion: Serum Heparin-binding protein serves as a non-invasive potential marker of acute bacterial meningitis even in partially treated cases.

Epidemiología de las meningitis bacterianas en niños en un hospital pediátrico: 2011-2016 / Epidemiology of bacterial meningitis in children at a pediatric hospital: 2011-2016

Introducción: Las meningitis bacterianas en niños son causa de importante morbimortalidad. Los principales agentes etiológicos son Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae. En los últimos años, luego de la introducción sucesiva de vacunas conjugadas al calendario nacional de inmunizaciones, se ha visto un cambio en la epidemiología de estas infecciones. Objetivo: Describir las características clínicas, epidemiológicas y evolutivas de los niños hospitalizados con meningitis bacteriana confirmada microbiológicamente entre 2011 y 2016 en un hospital de tercer nivel de complejidad. Materiales y métodos: Cohorte retrospectiva. Se incluyeron niños entre 1 mes de vida y 17 años con cuadro clínico compatible con meningitis bacteriana y cultivo positivo y/o PCR en líquido cefalorraquídeo y/o hemocultivos positivos para Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b. Se registraron las características demográficas, clínicas y evolutivas hasta los 30 días del egreso. Se utilizó mediana y rango intercuartilo (RIC) para variables continuas y porcentaje para variables categóricas. Se utilizó Stata 10. Resultados: n=65. Edad: mediana de 9 meses (RIC 4-35). Varones: 58% (n=38). Se identificó Neisseria meningitidis en un 48% (n=31), Haemophilus influenzae b en un 26% (n=17) y Streptococcus pneumoniae en un 26% (n=17). El 26% (n=17) de los pacientes presentaba alguna comorbilidad. Tuvieron hemocultivos positivos el 62% (n = 40) de los pacientes y 86% (n=55) de los líquidos cefalorraquídeos. Todos los pacientes recibieron tratamiento antimicrobiano con ceftriaxona tanto como tratamiento empírico como definitivo y 92% (n=60) recibieron corticoides empíricos. La mediana de días de internación fue de 11 (RIC 8-17). El 28% (n=18) requirió cuidados intensivos, y el 8% (n=5) falleció. Durante el período de estudio se observó que la frecuencia de meningitis por Streptococcus pneumoniae disminuyó en el final del estudio (9% en 2016 vs 60% en 2011), mientras que la frecuencia de meningitis por Neisseria meningitidis en 2016 fue mayor que al inicio del período (64% en 2016 vs. 40% en 2011). La frecuencia de identificación de Haemophilus influenzae b se mantuvo estable. Conclusiones: Las meningitis bacterianas confirmadas por Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b prevalecieron en niños menores de 12 meses. En esta cohorte se observó un predominio de las infecciones por Neisseria meningitidis en los últimos años, y una disminución en la frecuencia de meningitis por Streptococcus pneumoniae en el período post introducción de la vacuna conjugada 13 valente al calendario nacional de inmunizaciones. (AU)

Introduction: In children, bacterial meningitis is an important cause of morbidity and mortality. The main etiological agents are Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Over the last years, the successive introduction of conjugated vaccines in the national immunization calendar has led to a change in the epidemiology of these infections. Objective: To describe the clinical and epidemiological features and outcome of children admitted because of microbiologically confirmed meningitis seen between 2011 and 2016 at a tertiary care hospital. Material and methods: A retrospective cohort study was conducted. Children between 1 month of life and 17 years of age with clinical features compatible with bacterial meningitis and positive cultures and/or PCR in cerebrospinal fluid (CSF) and/or positive blood cultures for Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were included. Demographic, clinical, and outcome features were recorded until 30 days after discharge. Median and interquartile range (IQR) were calculated for continuous variables and percentages for categorical variables. The Stata 10 program was used. Results: n=65. Age: median was 9 months (IQR 4-35). Boys: 58% (n=38). Neisseria meningitidis was identified in 48% (n=31), Haemophilus influenzae b in 26% (n=17), and Streptococcus pneumoniae in 26% (n=17). Overall, 26% (n=17) of the patients presented with comorbidities. Positive blood cultures were found in 62% (n = 40) and positive CSF cultures in 86% (n=55) of the patients. All patients received antimicrobial treatment with ceftriaxone both empirically and as final treatment and corticosteroids were empirically started in 92% (n=60). Median hospital stay was 11 days (IQR 8-17). Overall, 28% (n=18) required intensive care and 8% (n=5) of the patients died. The incidence of meningitis due to Streptococcus pneumoniae was observed to diminish at the end of the study period (9% in 2016 vs 60% in 2011), while the incidence of meningitis due to Neisseria meningitidis in 2016 was higher than at the end of the study period (64% in 2016 vs. 40% in 2011). The frequency of identification of Haemophilus influenzae b remained stable. Conclusions: Confirmed bacterial infections due to Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were prevalent in infants younger than 12 months of age in this cohort of patients. Infections due to Neisseria meningitidis predominated over the last years and the incidence of meningitis due to Streptococcus pneumoniae diminished after the introduction of the 13 valent conjugated vaccine was introduced in the national immunization calendar.(AU)

Caracterización clínica de la meningitis aguda de la comunidad causada por Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae y Listeria monocytogenes en adultos en el Hospital Carlos van Buren entre los años 2013 y 2016 / Clinical characteristics of community-acquired acute meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Listeria monocytogenes in adults in Carlos van Buren Hospital between 2013-2016

INTRODUCCIÓN: la meningitis bacteriana es una enfermedad infecciosa aguda grave, que por su letalidad y costos en atención de salud genera un alto impacto en Salud Pública. Los agentes causales más frecuentes son Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae y Listeria monocytogenes, pero poco conocemos de nuestra realidad local. MATERIALES Y MÉTODOS: estudio descriptivo, con revisión de base de datos del laboratorio de microbiología del Hospital Carlos Van Buren, obteniendo datos de los cultivos de líquido céfalo raquídeo de pacientes mayores de 15 años entre marzo de 2013 y noviembre de 2016. RESULTADOS: 128 casos de meningitis bacteriana aguda, de los cuales 17 fueron por los microorganismos objetivos del estudio, siendo el más frecuente S. pneumoniae, clínicamente un 58% se presentó sin signos meníngeos. A 30 días del diagnóstico un 35% había fallecido, la mitad de ellos inició el tratamiento antibiótico pasadas las 24 horas desde su ingreso al hospital. En el 46% la tinción gram no evidenció bacterias. DISCUSIÓN: los microorganismos clásicamente descritos como agentes causales parecen no explicar la totalidad de los cuadros de meningitis bacteriana aguda en la población adulta estudiada, la ausencia de signos meníngeos no permite descartar la sospecha diagnóstica. La mitad de los pacientes fallecidos inició el tratamiento antibiótico pasadas las primeras 24 horas.

INTRODUCTION: bacterial meningitis is a serious acute infectious disease whose lethality and elevated health costs have a serious impact on public health. The most frequent causes are Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenza and Listeria monocytogenes, but we know little of the local situation. MATERIALS AND METHODS: A descriptive study reviewing Carlos van Buren Hospital´s microbiology laboratory data base, and obtaining the details of cerebrospinal fluid cultures of patients over the age of 15 between March 2013 and November 2016. RESULTS: 128 cases of acute bacterial meningitis of which 17% were caused by the micro-organisms of study, the most frequent being Streptococcus pneumoniae. 58% of patients had no meningeal signs. At 30 days from diagnosis 35% had died, half of these having started antibiotic treatment over 24 hours after admission. 46% of the Gram stains showed no bacteria. DISCUSSION: the classical infectious agents do not appear to account for the totality of acute bacterial meningitis in the population studied. The absence of meningeal signs should not rule out the diagnosis. Half of the patients who died started antibiotic treatment after the first 24 hours.

Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children / Comparação da pesquisa de enterovírus no liquor com Escore de Meningite Bacteriana em crianças

ABSTRACT Objective To measure the role of enterovirus detection in cerebrospinal fluid compared with the Bacterial Meningitis Score in children with meningitis. Methods A retrospective cohort based on analysis of medical records of pediatric patients diagnosed as meningitis, seen at a private and tertiary hospital in São Paulo, Brazil, between 2011 and 2014. Excluded were patients with critical illness, purpura, ventricular shunt or recent neurosurgery, immunosuppression, concomitant bacterial infection requiring parenteral antibiotic therapy, and those who received antibiotics 72 hours before lumbar puncture. Results The study included 503 patients. Sixty-four patients were excluded and 94 were not submitted to all tests for analysis. Of the remaining 345 patients, 7 were in the Bacterial Meningitis Group and 338 in the Aseptic Meningitis Group. There was no statistical difference between the groups. In the Bacterial Meningitis Score analysis, of the 338 patients with possible aseptic meningitis (negative cultures), 121 of them had one or more points in the Bacterial Meningitis Score, with sensitivity of 100%, specificity of 64.2%, and negative predictive value of 100%. Of the 121 patients with positive Bacterial Meningitis Score, 71% (86 patients) had a positive enterovirus detection in cerebrospinal fluid. Conclusion Enterovirus detection in cerebrospinal fluid was effective to differentiate bacterial from viral meningitis. When the test was analyzed together with the Bacterial Meningitis Score, specificity was higher when compared to Bacterial Meningitis Score alone.

RESUMO Objetivo Avaliar o papel da pesquisa de enterovírus no líquido cefalorraquidiano em comparação com o Escore de Meningite Bacteriana em crianças com meningite. Métodos Coorte retrospectiva, realizada pela análise de prontuários, incluindo pacientes pediátricos, com diagnóstico de meningite e atendidos em um hospital privado e terciário, localizado em São Paulo, entre 2011 e 2014. Foram excluídos os pacientes com doença crítica, púrpura, derivação ventricular ou neurocirurgia recente, imunossupressão, outra infecção bacteriana concomitante que necessitasse de antibioticoterapia parenteral e aqueles que receberam antibiótico 72 horas antes da punção lombar. Resultados Foram incluídos no estudo 503 pacientes. Destes, 64 foram excluídos e 94 não realizaram todos os exames para análise. Dos 345 pacientes restantes, 7 ficaram no Grupo de Meningite Bacteriana e 338 no Grupo de Meningite Asséptica. Não houve diferença estatística entre os grupos. Na análise do Escore de Meningite Bacteriana, dos 338 pacientes com possível meningite asséptica (culturas negativas), 121 deles tiveram um ou mais pontos para o Escore de Meningite Bacteriana, com valor de sensibilidade de 100%, especificidade de 64,2% e valor preditivo negativo de 100%. Dos 121 pacientes com Escore de Meningite Bacteriana positivo, 71% (86 pacientes) tiveram a pesquisa de enterovírus positiva no líquido cefalorraquidiano. Conclusão A pesquisa de enterovírus no líquido cefalorraquidiano mostrou-se eficaz em diferenciar a meningite bacteriana da viral. Analisada junto com o Escore de Meningite Bacteriana, a especificidade foi maior em comparação ao Escore de Meningite Bacteriana isolado.

Meningitis bacteriana aguda por Streptococcus agalactiae en una mujer no embarazada asociada a una fístula de LCR: comunicación de un caso / Acute bacterial meningitis by Streptococcus agalactiae in a non pregnant woman associated to a cerebrospinal fluid leak: a case report

Streptococcus agalactiae is a rare cause of acute bacterial meningitis. We report the case of a middle age non-pregnant female patient, with no comorbitidies, who was hospitalized with acute meningitis. The pathogen was identified both in blood and CSF. She recovered uneventfully with ceftriaxone and dexamethasone. A CSF leak was suspected by previous history of unilateral watery rhinorrhea, that was demonstrated with a high resolution paranasal sinus CT and beta-2 transferrin analysis of the nasal fluid. Vulvovaginitis was also diagnosed after admission, but no cultures were obtained. Streptococcus agalactiae is an infrequent cause of bacterial meningitis that should promote the search of anatomical abnormalities or comorbidities in non-pregnant adults and beyond newborn period.

Streptococcus agalactiae es una causa infrecuente de meningitis bacteriana aguda. Comunicamos el caso de una mujer de edad media sin co-morbilidades que ingresó por un cuadro de meningitis producido por este patógeno, el que también fue identificado en hemocultivos. La paciente se trató con ceftriaxona y corticoesteroides i.v., recuperándose satisfactoriamente. Por el antecedente de una rinorrea acuosa unilateral, se sospechó una fístula de LCR, la que se demostró con una tomografía computada multicorte de senos paranasales y por una prueba de ß2 transferrina en fluido nasal. En forma concomitante se diagnosticó una vulvovaginitis sin estudio microbiológico. Streptococcus agalactiae es una causa infrecuente de meningitis bacteriana que si no se presenta asociada al embarazo o en neonatos, obliga a la búsqueda de anormalidades anatómicas o co-morbilidades.

Prediction of bacterial meningitis based on cerebrospinal fluid pleocytosis in children

Children with cerebrospinal fluid pleocytosis are frequently treated with parenteral antibiotics, but only a few have bacterial meningitis. Although some clinical prediction rules, such as bacterial meningitis score, are of well-known value, the cerebrospinal fluid white blood cells count can be the initial available information. Our aim was to establish a cutoff point of cerebrospinal fluid white blood cell count that could distinguish bacterial from viral and aseptic meningitis. A retrospective study of children aged 29 days to 17 years who were admitted between January 1st and December 31th, 2009, with cerebrospinal fluid pleocytosis (white blood cell > 7 µL-1) was conducted. The cases of traumatic lumbar puncture and of antibiotic treatment before lumbar puncture were excluded. There were 295 patients with cerebrospinal fluid pleocytosis, 60.3% females, medium age 5.0 ± 4.3 years distributed as: 12.2% 1-3 months; 10.5% 3-12 months; 29.8% 12 months to 5 years; 47.5% >5 years. Thirty one children (10.5%) were diagnosed with bacterial meningitis, 156 (52.9%) viral meningitis and 108 (36.6%) aseptic meningitis. Bacterial meningitis was caused by Neisseria meningi tidis (48.4%), Streptococcus pneumoniae (32.3%), other Streptococcus species (9.7%), and other agents (9.7%). cerebrospinal fluid white blood cell count was significantly higher in patients with bacterial meningitis (mean, 4839 cells/µL) compared to patients with aseptic meningitis (mean, 159 cells/µL, p < 0.001), with those with aseptic meningitis (mean, 577 cells/µL, p < 0.001) and with all non-bacterial meningitis cases together (p < 0.001). A cutoff value of 321 white blood cell/µL showed the best combination of sensitivity (80.6%) and specificity (81.4%) for the diagnosis of bacterial meningitis (area under receiver operating characteristic curve 0.837). Therefore, the value of cerebrospinal fluid white blood cell count was found to be a useful and rapid diagnostic test to distinguish between bacterial and nonbacterial meningitis in children.

The Causes and Treatment Outcomes of 91 Patients with Adult Nosocomial Meningitis

BACKGROUND/AIMS: Frequent pathogens of nosocomial meningitis were investigated and the adequacy of empiric antibiotic therapy was assessed. Outcomes of nosocomial meningitis were also evaluated. METHODS: Ninety-one patients, who were diagnosed and treated for nosocomial meningitis at a single tertiary hospital in Daegu, Korea for 10 years, were included. Medical record and electronic laboratory data on the causative pathogens, antibiotics used, and outcomes were retrospectively investigated. RESULTS: Coagulase-negative Staphylococcus (40.9%) was the most common pathogen, followed by Acinetobacter (32.5%). Both were cultured as a single organism in cerebrospinal fluid (CSF). Seventy-eight patients (85.7%) had infections related to external ventricular drains (EVD). The most common empirical antibiotics were extended-spectrum beta-lactam antibiotics plus vancomycin (35/91, 38.6%). Of the 27 patients who had cultured Acinetobacter in CSF, 10 (37%) were given the wrong empirical antibiotic treatment. Seven of the 27 patients (26.9%) with cultured Acinetobacter died, and overall mortality of the 91 patients was 16.5%. In the multivariate analysis, the presence of combined septic shock (p < 0.001) and a persistent EVD state (p = 0.021) were associated with a poor prognosis. CONCLUSIONS: Acinetobacter is one of the leading pathogens of nosocomial meningitis and may lead to inadequate coverage of empiric antibiotic therapy due to increasing resistance. An EVD should be removed early in cases of suspected nosocomial meningitis, and carbapenem might be required for the poor treatment response.

IL-6 and IL-8 in cerebrospinal fluid from patients with aseptic meningitis and bacterial meningitis: their potential role as a marker for differential diagnosis

Cytokines are molecules that act as mediators of immune response; cerebral spinal fluid (CSF) IL-6 is found in all meningeal inflammatory diseases, but IL-8 is associated with acute bacterial meningitis (ABM). A case control study was done to ascertain the discriminatory power of these cytokines in differentiating ABM from aseptic meningitis (AM); IL-6 and IL-8 CSF concentrations were tested through ELISA in samples collected from patients who underwent investigation for meningitis. Sixty patients, 18 with AM, nine with bacteriologic confirmed ABM and 33 controls, assisted in 2005 (MA and controls) and 2007 (ABM) were included. Differently from controls, IL-6 concentrations were increased both in MA and ABM patients (p < 0.05). CSF IL-8 levels were higher in ABM than in AM and controls (p < 0.05). Discriminatory power in ABM as assessed by the area under receiver operator (ROC) curve was 0.951 for IL-8, using a cut-off of 1.685 ng/dL (100 percent of sensitivity and 94 percent of specificity). The CSF concentration of both IL-6 and IL-8 are increased in the presence of meningeal inflammation, IL-8 could be an important tool to differentiate ABM from AM.

Neurosífilis meningovascular y gomatosa cerebral concomitante, en paciente seronegativo para virus de inmunodeficiencia humana / Meningovascular neurosyphilis and concomitant syphilitic gummata in hiv-seronegative patients

Neurosyphilis (NS) is caused by the presence of Treponema Pallidum (TP) spirochete within the Central Nervous System (CNS), mainly affecting the meninges and cerebrospinal fluid (CSF). 5 percent to 10 percent of untreated syphilitic patients are deemed to develop symptomatic NSÕ. Its incidence and clinical spectrum have changed over the years with prevalence of early clinical stages of meningitic and meningovascular (MV) NS and exceptional occurrence of late clinical stages (tabes dorsalis, general paresis, and gummata) in the age of antibiotics. The case under analysis deals with aggressive MV and concomitant brain gumma (BG) NS. The case subject is a human inmunodeficiency virus (HIV)-seronegative, 44-year-old woman with 2-year symptomatic latency. Her medical record showed recurrent sensorimotor vascular involvement, fast cognitive damage and chronic, daily cephalea. She met clinical diagnosis, cerebrospinal fluid and serologic criteria for NS. Brain computerized tomography (CT) and magnetic resonance (MR) reported lenticulostriate artery infarction and bilateral ganglionic syphilitic gummata. She underwent Penicillin G-based treatment, making progress with neurological, cognitive-motor sequelae. Although NS has anticipated and speeded up its several clinical stages in connection with HIV/Syphilis co-infection, the peculiarity of this case is the concurrence of early and late NS manifestations in HIV-seronegative patient. The conclusion is that NS is a disease that still prevails and that appropriate diagnosis and treatment prevent irreversible neurological sequelae.

La Neurosífilis (NS) es causada por la invasión del Sistema Nervioso Central (SNC) por la espiroqueta Treponema Pallidum (TP), afectando primariamente las meninges y líquido cefalorraquídeo. Entre 5 a 10 por ciento de los pacientes sifilíticos no tratados desarrollarán una NS sintomáticaÕ. Su incidencia y espectro clínico ha cambiado a lo largo del tiempo, siendo las formas clínicas precoces meníngea y meningovascular (MV) las más prevalentes. En contraste, las formas tardías (tabes dorsal, parálisis general y gomas) son de ocurrencia excepcional en la era antibiótica. Se analiza un caso de NS menigovascular y gomas cerebrales concomitantes, de curso clínico agresivo. En una mujer de 44 años, seronegativa para virus de inmunodeficiencia humana (VIH), con latencia sintomática de dos años. Presentaba una historia de focalidad sensitivo-motor de perfil vascular recurrente, rápido deterioro cognitivo-motor y cefalea crónica diaria. Cumplía criterios diagnósticos clínicos, licuorales y serológicos para NS. La Tomografía computada (TC) y Resonancia Magnética (RM) cerebral mostró infartos arteriolares lentículo-estriados y gomas sifilíticas ganglionares bilaterales. Recibió tratamiento con Penicilina G, evolucionando con secuelas neurológicas cognitivas-motoras. Si bien, la NS actualmente, ha anticipado y acelerado sus diferentes formas clínicas en relación a co-infección VIH/Sífilis. Lo llamativo de este caso, es la presentación concomitante de con manifestaciones precoces y tardías de NS en paciente VIH seronegativo. Se concluye que la NS sigue siendo una enfermedad vigente y su diagnóstico y tratamiento oportuno previene secuelas neurológicas irreversibles.

Specific PCR assay for rapid and direct detection of Neisseria meningitidis in cerebrospinal fluid specimens

Neisseria meninigitidis is one of the most frequently encountered microorganisms associated with central nervous system infections. The aim of this study was to evaluate a PCR-based assay for specific and rapid detection of N. meninigitidis in CSF specimens. Since April 2002 to July 2006, 130 CSF specimens were collected from patients suspected of having baterial meningitis. Bacterial isolation and identification was carried out according to the standard bacteriological methods. The PCR was used to amplify a 101bp fragment of capsular transport gene A [ctr A] of N. meningitidis. PCR yielded an amplified product with the expected size of 101 base pair fragment. Sensitivity test proved 500 mg of N. meningitidis DNA as the final detection limit and specificity test revealed no cross-reaction for a wide range of respiratory pathogenic organisms. The PCR assay was more sensitive than the bacterial culturing. It might be possible to apply this procedure for rapid diagnosis of meningococci in clinical samples

Niveles de lactato en líquido cefalorraquídeo y su relación con meningitis bacteriana en pediatría / Lactate levels in cerebrospinal fluid and its relationship with bacterial meningitis in children

El líquido cefalorraquídeo (LCR) proporciona un sostén mecánico y contribuye al control del medio químico cerebral. La meningitis es la más común de las infecciones que afectan el sistema nervioso central (SNC) y puede progresar rápidamente produciendo un daño cerebral importante. En la meningitis bacteriana (MB) se produce una disminución de la irrigación cerebral, seguida de hipoxia, catabolismo anaeróbico con formación de ácido láctico (AL) y aumento de su nivel en LCR. Con el fin de realizar un diagnóstico precoz se estudiaron los niveles de AL intentando demostrar la importancia de la determinación de este parámetro, correlacionar sus niveles con los de otros componentes y obtener valores límite para diferenciar los distintos grupos en la población pediátrica. Se realizó un estudio prospectivo en el cual se procesaron muestras de pacientes internados y/o atendidos en el servicio de emergencia del Hospital de Niños de Córdoba, Argentina, con sospecha de meningitis. El aumento de los niveles de lactato fue uno de los datos más confiables en el diagnóstico de meningitis bacteriana al ser comparado con el resto de los parámetros estudiados, diferenciándose del grupo control o con encefalitis viral. Los niveles de AL y lactato dehidrogenasa (LD) permitieron observar subpoblaciones según la virulencia del agente causal e intensidad del cuadro patológico en el grupo con MB.

Cerebrospinal fluid (CSF) provides mechanical support and contributes to the control of the cerebral chemical environment. Meningitis is the most common of the infections that affect the nervous central system and can progress rapidly producing important brain damage. Bacterial meningitis gives rise to a reduction in the irrigation of the brain, followed by hypoxia, anaerobic catabolism with the formation of lactic acid (LA) and increase in its level in cerebrospinal fluid. In order to carry out an earlier diagnosis, lactic acid levels were studied, trying to demonstrate the importance of the determination of this parameter, correlate the levels with those of other components, and obtain limit values to differentiate the different groups in the paediatric population. A prospective study was performed in which samples of patients suspected of having meningitis, who were admitted into hospital and/or attending the emergency service of the Children's Hospital of Cordoba, Argentina were analysed. The increase in the levels of lactate was one of the most reliable pieces of information in the diagnosis of BM, comparing it with the rest of the parameters studied and differentiating it from the control group or with viral encephalitis. The levels of LA and lactate dehydrogenase (LD) enabled the observation of subpopulations according to the virulence of the causal agent and the intensity of the pathological manifestations in the BM group.

Culture- and antigen-negative meningitis in Guatemalan children / Meningitis negativa a pruebas antigénicas y de cultivo en niños guatemaltecos

OBJECTIVE: To compare children with confirmed bacterial meningitis (CBM) and those with culture- and latex-negative meningitis (CLN). METHODS: Children 1 to 59 months of age admitted to three major referral hospitals in Guatemala City with clinical signs compatible with bacterial infections were evaluated prospectively between 1 October 1996 and 31 December 2005. Bacterial cultures and latex agglutination antigen testing were performed on samples of cerebrospinal fluid (CSF). RESULTS: The case-fatality rate was significantly higher in the 493 children with CBM than in the 528 children with CLN (27.6 percent and 14.9 percent, respectively; P < 0.001). Children with CBM were less likely to have received antibiotics and more likely to have seizures, shock, or coma on admission than children with CLN. Among the 182 CBM survivors and 205 CLN survivors studied between October 2000 and December 2005, clinically observed sequelae were present at discharge in a higher percentage of the CBM than of the CLN group (78.6 percent and 46.8 percent, respectively; P < 0.0001). CSF glucose < 10 mg/dL, peripheral neutrophils < 2 000 cells/mm³, coma or shock at admission, and concurrent sepsis or pneumonia were risk factors for mortality in children with CBM; only coma or shock at admission predicted mortality in children with CLN. CONCLUSIONS: The high case-fatality and sequelae rates suggest that many children with CLN may have had bacterial meningitis. Estimates based on confirmed meningitis alone underestimate the true vaccine-preventable disease burden. Additional studies to determine etiologies of CLN in this population are indicated.

OBJETIVO: Comparar los casos infantiles de meningitis bacteriana confirmada (MBC) y meningitis negativa a pruebas de látex y de cultivo (MNLC). MÉTODOS: Se evaluaron los niños de 1 a 59 meses de edad ingresados en tres grandes hospitales de referencia de la Ciudad de Guatemala entre el 1 de octubre de 1996 y el 31 de diciembre de 2005 con signos clínicos de infección bacteriana. Se realizaron cultivos bacterianos y pruebas de aglutinación antigénica con látex en muestras de líquido cefalorraquídeo (LCR). RESULTADOS: La tasa de letalidad fue significativamente mayor en los 493 niños con MBC que en los 528 niños con MNLC (27,6 por ciento y 14,9 por ciento, respectivamente; P < 0,001). Los niños con MBC tuvieron menor probabilidad de recibir antibióticos y mayor de sufrir convulsiones, choques o entrar en coma al ser ingresados que los niños con MNLC. Se observó un mayor porcentaje de manifestaciones clínicas de secuelas al alta hospitalaria en los 182 niños sobrevivientes con MBC que en los 205 sobrevivientes con MNLC estudiados entre octubre de 2000 y diciembre de 2005 (78,6 por ciento y 46,8 por ciento, respectivamente; P < 0,0001). Los factores de riesgo de muerte en los niños con MBC fueron: glucosa en LCR < 10 mg/dL, neutrófilos periféricos < 2 000 células/mm³, coma o choque al ingreso, y sepsis o neumonía concurrentes; solo el coma y el choque al ingreso predijeron la muerte en niños con MNLC. CONCLUSIONES: Las altas tasas de letalidad y de secuelas indican que muchos niños con MNLC pueden haber tenido meningitis bacteriana. Las estadísticas basadas solamente en los casos confirmados de meningitis subestiman la verdadera carga de enfermedad prevenible mediante vacuna. Se deben emprender estudios adicionales para determinar las etiologías de la MNLC en esta población.

¿Es necesaria la punción lumbar en la evaluación del recién nacido febril sin signos de focalización? / ¿Is it necessary to perform a lumbar puncture in the evaluation of the febrile newborn infant without source?

La evaluación del RN febril incluye efectuar una punción lumbar para detectar un foco meníngeo. Objetivo: Evaluar la utilidad de este procedimiento al ingreso del paciente al hospital y, eventualmente, en una segunda instancia si se justifica clínicamente. Pacientes y Método: Estudiamos 1.841 recién nacidos febriles sin signos de focalización que consultaron en la Unidad de Emergencia entre enero 1992 y diciembre 2000. Todos se sometieron a una evaluación para pesquisa de sepsis. Calculamos la tasa de incidencia de meningitis, y analizamos la frecuencia de meningitis diagnosticada en la evaluación inicial y en una re-evaluación. Resultados: Hubo 206 pacientes con diagnóstico de meningitis (incidencia de 11,2 por ciento), de las cuales 20 fueron bacterianas (1,1 por ciento) y 186 meningitis asépticas (10,1 por ciento). En la evaluación inicial se detectaron 155 pacientes con meningitis (155/ 1.774 = 8,7 por ciento) y en la reevaluación (media de 39,5 ± 25,2 horas más tarde) se diagnosticaron 51 casos más (51/ 135 = 37,8 por ciento). Conclusiones: La meningitis fue un diagnóstico frecuente en recién nacidos febriles sin signos de focalización, predominando la meningitis aséptica. En casi 25 por ciento de los casos se llegó a este diagnóstico mediante la ejecución de la punción lumbar al ser re-evaluados.

Lumbar puncture to detect bacterial meningitis is a recommended screening procedure to be performed in febrile newborn infants at admission to hospital. Objective: To evaluate the usefulness of this procedure performed at admission and eventually, in a second look if clinically justified. Patients and method: There were studied 1,841 febrile newborns consulting at the Emergency Department from January 1992 to December 2000 without source. All of them underwent a sepsis workup. The rate of meningitis incidence was calculated, and we analyzed the frequency of meningitis diagnosed in the initial evaluation and reappraisal. Results: There were 206 febrile patients with diagnosis of meningitis for an incidence of 11.2 percent, which 20 were bacterial (1.1 percent) and 186 aseptic meningitis (10.1 percent). In the initial evaluation 155 patients were diagnosed with meningitis (155/ 1.774 = 8.7 percent) and in reappraisal (mean 39,5 ± 25,2 hours after) there were diagnosed another 51 cases (51/ 135 = 37.8 percent). Conclusions: The meningitis was a common diagnosis in febrile newborns without source, with prevalence of aseptic meningitis. In almost 25 percent of cases we reached to this diagnosis by means of performing lumbar puncture after a reappraisal.

Importância do exame do liquor de controle em meningite bacteriana como critério de alta / Importance of cerebrospinal fluid control tests in bacterial meningitis cases as a discharge criterion

Há controvérsias sobre indicação do exame do liquor de controle em pacientes recuperados clinicamente de meningite bacteriana como critério de cura. Alguns autores defendem alta hospitalar após normalização clínica e liqüórica, outros que a análise do liquor não se justifica em todos os pacientes. Esta série de casos com comparação de grupos investiga alterações no exame liqüórico de controle e avalia a importância do exame na decisão da alta. De 297 pacientes estudados, em 89,9 por cento, o liquor de controle não mudou a intenção de alta (liquor resolutivo), já em 10,1 por cento a alta foi suspensa (liquor não-resolutivo). Destes, o esquema antibiótico foi trocado em 30 por cento. Entre as variáveis que pudessem ser preditivas de liquor não-resolutivo, à admissão, proteinorraquia maior que 100mg/dL (p=0,04) e glicorraquia menor ou igual a 20mg/dL (p=0,03) associaram-se a chance 2,5 vezes maior, podendo ser úteis como critérios para indicar exame do liquor como controle de cura para alta.

There is controversy regarding indications for cerebrospinal fluid control tests on patients who have clinically recovered from bacterial meningitis, as a cure criterion. Some authors advocate discharge after confirmation of clinical and cerebrospinal fluid normalization, while others maintain that cerebrospinal fluid analysis is not justified in all cases. This case series with group comparisons investigated changes seen in cerebrospinal fluid control tests and evaluated the importance of this for the discharge decision. Out of 297 patients studied, the cerebrospinal fluid control test did not change the discharge intention in 89.9 percent of the cases (healed cerebrospinal fluid), while in 10.1 percent, the discharge was suspended (non-healed cerebrospinal fluid). Of these, the antibiotic scheme was changed in 30 percent. Among the variables that might predict the presence of non-healed cerebrospinal fluid on admission, cerebrospinal fluid protein levels higher than 100mg/dl (p = 0.04) and glycorrhachia lower than or equal to 20 mg/dl (p = 0.03) were associated with a 2.5-times greater chance. These may be useful as criteria for indicating cerebrospinal fluid control tests before discharge.