Clinical features of post-neurosurgical bacterial meningitis in children / 中华儿科杂志

Objective: To understand the characteristics of bacterial meningitis after pediatric neurosurgical procedures. Methods: This was a retrospective observational study. From January 2016 to December 2022, 64 children diagnosed with post-neurosurgical bacterial meningitis based on positive cerebrospinal fluid (CSF) culture in Department of Neurosurgery of Shanghai Children's Medical Center were selected as the study population. The clinical characteristics, onset time, routine biochemical indexes of cerebrospinal fluid before anti infection treatment, bacteriology characteristics and sensitivity to antibiotics of bacteria cultured from cerebrospinal fluid were analyzed. Based on the CSF culture results, the patients were divided into the Gram-positive bacteria infection group and the Gram-negative bacteria infection group. The clinical characteristics of the two groups were compared using t-tests or Wilcoxon rank-sum tests, and chi-square tests. Results: There were 64 children,42 boys and 22 girls, with onset age of 0.83 (0.50, 1.75) years. Seventy cases of post-neurosurgical bacterial meningitis occurred in the 64 children, of which 15 cases (21%) in spring, 23 cases (33%) in summer, 19 cases (27%) in autumn, and 13 cases (19%) in winter. The time of onset was 3.5 (1.0, 10.0) months after surgery; 15 cases (21%) occurred within the first month after the surgery, and 55 cases (79%) occurred after the first month. There were 38 cases (59%) showing obvious abnormal clinical manifestations, fever 36 cases (56%), vomiting 11 cases (17%). Forty-eight cases (69%) were caused by Gram-positive bacteria, with Staphylococcus epidermidis 24 cases; 22 cases (31%) were caused by Gram-negative bacteria, with Acinetobacter baumannii the prominent pathogen 7 cases. The Gram-positive bacterial infection was more common in summer than the Gram-negative bacterial infection (20 cases (42%) vs. 3 cases (14%), χ2=5.37, P=0.020), while the Gram-negative bacterial infection was more in autumn and within the first month after surgery than the Gram-positive bacterial infection (11 cases (50%) vs. 8 cases (17%), 15 cases (67%) vs. 5 cases (33%), χ2=8.48, 9.02; P=0.004, 0.003). Gram-positive bacteria resistant to vancomycin and Acinetobacter baumannii resistant to polymyxin were not found. However, Acinetobacter baumannii showed only 45% (10/22) susceptibility to carbapenem antibiotics. Conclusions: The clinical presentation of post-neurosurgical bacterial meningitis in children is atypical. Gram-positive bacteria are the main pathogens causing post-neurosurgical bacterial meningitis; Gram-negative bacterial meningitis are more likely to occur in autumn and within the first month after surgery. Acinetobacter baumannii has a high resistance rate to carbapenem antibiotics, which should be taken seriously.

Sepsis precoz, osteoartritis y meningitis: a propósito de un caso clínico / Early sepsis, osteoarthritis and meningitis: a clinical case / Sepse precoce, osteoartrite e meningite: relato de caso

Se expone el caso de un recién nacido que desarrolló sepsis connatal precoz a Streptococcus agalactiae, con meningitis aguda supurada y osteoartritis de rodilla izquierda. Como factor de riesgo la madre no tenía realizado el exudado rectovaginal, pesquisa que detecta la colonización por estreptococo del grupo B (EGB). Se aisló el germen en hemocultivo y en líquido de punción articular. Recibió tratamiento antibiótico adecuado a la sensibilidad del microorganismo y según pauta de sepsis con meningitis, evolucionando favorablemente. En este trabajo se describe la epidemiología de la sepsis neonatal y los cambios ocurridos luego de la implementación de la profilaxis antibiótica en el preparto.

We hereby present the case of a newborn with early connatal sepsis due to Streptococcus agalactiae, with acute suppurative meningitis and left knee osteoarthritis. As a risk factor, the mother had not performed the rectus vaginal exudate screening that detects colonization by Group B Streptococcus (GBS). The germ was isolated in blood culture and in joint puncture fluid. The patient received germ-sensitive antibiotic treatment for meningitis sepsis and evolved favorably. This paper describes the epidemiology of neonatal sepsis and the changes that have occurred after the administration of the antibiotic prophylaxis during pregnancy.

Apresentamos o caso de um recém-nascido com sepse neonatal precoce por Streptococcus agalactiae, com meningite supurativa aguda e osteoartrite de joelho esquerdo. Como fator de risco, a mãe não realizou teste de exsudato vaginal do reto que detecta a colonização por estreptococos do grupo B (SGB). O germe foi isolado em hemocultura e líquido de punção articular. A paciente recebeu tratamento com antibióticos germinativos para padrão meningite sepse e evoluiu favoravelmente. Este artigo descreve a epidemiologia da sepse neonatal e as mudanças ocorridas após a administração da profilaxia antibiótica durante a gravidez.

Meningite bacteriana: uma revisão / Bacterial meningitis: a review

A meningite bacteriana é uma inflamação das leptomeninges que envolvem o Sistema Nervoso Central. Essa patologia, que possui diversos agentes etiológicos, apresenta-se na forma de síndrome, com quadro clínico grave. Entre as principais bactérias que causam a meningite, estão a Neisseria meningitis e Streptococcus pneumoniae. A transmissão ocorre através das vias aéreas por meio de gotículas, sendo a corrente sanguínea a principal rota para as bactérias chegarem à barreira hematoencefálica e, a partir dessa, até as meninges. Atualmente existem vários métodos de diagnóstico precisos, onde a cultura de líquido cefalorraquidiano (LCR) é o método padrão ouro. Ademais, a melhora na qualidade do tratamento com beta-lactâmicos e a maior possibilidade de prevenção, devido à elevação do número e da eficácia de vacinas, vem contribuindo para redução dos casos da doença e de sua gravidade. Porém, apesar desses avanços, ainda há um elevado número de mortalidades e sequelas causadas por essa síndrome.

Bacterial meningitis is an inflammation of the leptomeninges that surround the Central Nervous System. This pathology, which has several etiological agents, is presented as a syndrome with a severe clinical scenario. The main bacteria causing meningitis include Neisseria meningitis and Streptococcus pneumoniae. It can be transmitted by droplets through the airways, with the bacteria using the bloodstream as the main route to reach the blood-brain barrier, and from there to the meninges. There are currently several accurate diagnostic methods, with CSF culture being the gold standard. In addition, the improvement in the quality of beta-lactam treatment and the greater possibility of prevention due to the increased number and effectiveness of vaccines have contributed to reducing the number of cases and severity of the disease. Nevertheless, despite these advances, this syndrome still presents a high number of mortalities and sequelae.

Diagnostic value of heparin-binding protein in the cerebrospinal fluid for purulent meningitis in children

This study aimed to investigate the diagnostic value of heparin-binding protein (HBP) in the cerebrospinal fluid of children with purulent meningitis (PM). This study included 118 children with PM diagnosed at our hospital from January 2018 to January 2020, 110 children with viral meningitis (VM) and 80 children with suspected meningitis who were ruled out by cerebrospinal fluid (CSF) analysis during the same period. HBP and white blood cell (WBC) count in the CSF, and inflammatory factors, including C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and procalcitonin (PCT), were measured. Receiver-operator characteristic curves were used to analyze the predictive value of HBP, CRP, PCT, and TNF-α levels in the diagnosis of PM by CSF analysis. HBP levels in the CSF of children with PM were higher, while the CRP and serum PCT and TNF-α levels were elevated in all groups (P<0.05). In addition, HBP levels in the CSF were more accurate for the diagnosis of PM than traditional diagnostic indexes. HBP levels in the CSF can be used as an important reference for early diagnosis of PM.

Polymerase chain reaction targeting 16S ribosomal RNA for the diagnosis of bacterial meningitis after neurosurgery

OBJECTIVES: Bacterial and aseptic meningitis after neurosurgery can present similar clinical signs and symptoms. The aims of this study were to develop and test a molecular method to diagnose bacterial meningitis (BM) after neurosurgery. METHODS: A 16S ribosomal RNA gene PCR-based strategy was developed using artificially inoculated cerebrospinal fluid (CSF) followed by sequencing. The method was tested using CSF samples from 43 patients who had undergone neurosurgery and were suspected to suffer from meningitis, and from 8 patients without neurosurgery or meningitis. Patients were classified into five groups, confirmed BM, probable BM, possible BM, unlikely BM, and no meningitis. RESULTS: Among the samples from the 51 patients, 21 samples (41%) were culture-negative and PCR-positive. Of these, 3 (14%) were probable BM, 4 (19%) were possible BM, 13 (62%) were unlikely BM, and 1 (5%) was meningitis negative. Enterobacterales, non-fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii), Staphylococcus haemolyticus, Granulicatella, Variovorax, and Enterococcus cecorum could be identified. In the group of patients with meningitis, a good agreement (3 of 4) was observed with the results of cultures, including the identification of species. CONCLUSION: Molecular methods may complement the diagnosis, guide treatment, and identify non-cultivable microorganisms. We suggest the association of methods for suspected cases of BM after neurosurgery, especially for instances in which the culture is negative.

Meningitis por Salmonella Enteritidis en un lactante: comunicación de un caso y revisión de la literatura / Salmonella Enteritidis meningitis in an infant: case report and literature review

Resumen La meningitis por Salmonella spp. es infrecuente en pediatría, pero debe sospecharse especialmente en menores de seis meses. Salmonella subespecie enterica es la más frecuente a nivel mundial, siendo el serovar Enteritidis el más importante. Tiene una alta tasa de complicaciones, predominando las colecciones y abscesos, por lo que se recomienda realizar una neuroimagen a todos los pacientes. A pesar que el manejo no está estandarizado, hay consenso en que el tratamiento de elección son las cefalosporinas de tercera generación. La resistencia antimicrobiana es infrecuente pero va en aumento, principalmente en países subdesarrollados. Presentamos el primer caso publicado en Chile de una meningitis por S. Enteritidis en un lactante de 11 meses, que se presentó con fiebre y una convulsión focalizada, con hemocultivos y cultivo de líquido cefalorraquídeo positivos. El paciente completó tratamiento con ceftriaxona y ciprofloxacina por cuatro semanas con buena respuesta.

Abstract Salmonella spp meningitis is rare in pediatrics. However, it should be especially suspected in children younger than 6 months. The enteric subspecies is the most frequent worldwide, with the Enteritidis serovar being the most important. The complication rate is high, with collections and abscesses predominating. For this reason, neuroimaging is currently recommended for all patients. Even though management is not standardized, there is consensus that first line treatment should be with third generation cephalosporins. Antibiotic resistance is infrequent but increasing, mainly in underdeveloped countries. We present the first case reported in Chile of meningitis by Salmonella Enteritidis in an 11-month-old infant presenting with fever and focused epileptic crisis. Blood culture and cerebrospinal fluid culture were positive. The patient completed four weeks of treatment with ceftriaxone and ciprofloxacin with a good response.

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.

Infecciones postneuroquiróºrgicas: Puesta al día y recomendaciones intersociedades / Post-neurosurgical infections. Update and intersociety recommendations

Las infecciones asociadas a procedimientos neuroquiró;ºrgicos son complicaciones graves que contribuyen a la morbimortalidad de los pacientes neurocríticos, así como tambín a la prolongació;n de la estancia en la UTI y/o en el hospital. El diagnó;stico es complejo ya que no se dispone de gold standard y se apoya en la sospecha clínica, las alteraciones físico-químicas del líquido cefalorraquídeo y el aislamiento microbiano. El tratamiento debe ser precoz y guiado por la epidemiología local. La duració;n dependerá del microorganismo causal, su sensibilidad y la disponibilidad de tratamientos antibió;ticos efectivos en el sitio de la infecció;n. La implementació;n de medidas de prevenció;n con evidencia demostrada minimiza el riesgo de infecció;n. Esta puesta al día intersociedades SADI-SATI presenta datos epidemioló;gicos (internacionales y locales), mó;©todos diagnó;sticos, tratamiento, y pautas de prevenció;n, considerando las publicaciones más relevantes de los ó;ºltimos aó;±os sobre el tema.

Infections associated with neurosurgical procedures are serious complications that contribute to the morbidity and mortality of neurocritical patients, as well as to the prolongation of the stay in the ICU and the hospital. The diagnosis is complex since there is no gold standard, so it is based on clinical suspicion, CSF physical-chemical examination, and microbial isolation. Treatment should be initiated early, guided by local epidemiology. The duration will depend on the causative microorganism, its sensitivity and the availability of antibiotic treatments that are effective at the site of infection. The implementation of preventive measures with proven efficacy minimizes the risk of infection. This SADI-SATI intersociety update reviews relevant data recently published on this area at the national at international level regarding epidemiology, diagnostic methodologies, therapeutic approaches, and prevention guidelines.

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.

Meningitis caused by Salmonella enterica serotype Panama in Brazil: first case reported

Abstract Salmonella infections usually occur as gastroenteritis that is generally self-limited. However, some serotypes of Salmonella can cause severe extra-intestinal infections, such as bacteremia and meningitis. Here, we report the first Salmonella Panama case of meningitis in 4-month-old male newborn in Brazil. The invasive strain isolated was susceptible to all antimicrobial agents tested. The genes agfA, fimA, invA, sfbA, phoP, and slyA were detected using polymerase chain reactions. These findings are relevant and physicians should be alert to the possibility of meningitis in newborns due to S. Panama, which can present a high rate of mortality or recurrence of infection.

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.

Meningitis e hipoacusia por manipulación de carne porcina / Meningitis and hypoacusia due to swine meat handling

Resumen En Chile se han descrito ocasionalmente casos de meningitis zoonótica por Streptococcus suis ligados a criaderos de cerdos en el sur del país. Presentamos el caso de una mujer que desarrolló un cuadro de meningitis aguda bacteriana por este agente dos días después de manipular un cerdo faenado. No tenía crianza de cerdos ni visitaba granjas de animales. El diagnóstico fue establecido por el cultivo del LCR. Desarrolló una hipoacusia profunda que no mejoró a pesar del uso de corticoesteroides ni tratamiento antimicrobiano, sin otras complicaciones. La meningitis por S. suis es una condición emergente y ligada a porcinos en diferentes formas. La hipoacusia es una complicación frecuente con este agente.

Zoonotic meningitis by Streptococcus suis has been described occasionally in Chile and linked to pig farmers in the south of the country. We report a female case that developed acute bacterial meningitis by this agent, two days after handling a piece of raw swine meat. She did not participate on swine breeding nor visited farms. Diagnosis was obtained by CSF culture. A severe hearing loss and not recovered despite corticosteroids use and antimicrobial treatment, without others complications. Meningitis by S. suis is emerging as a new pathogen and linked to swine in different forms. Hypoacusis happens frequently with this agent.

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)

Utilização de escore e dosagem de lactato no líquor para diagnóstico diferencial entre meningite bacteriana e meningite asséptica / Use of score and cerebrospinal fluid lactate dosage in differential diagnosis of bacterial and aseptic meningitis

RESUMO Objetivo: Avaliar o Escore para Meningite Bacteriana (EMB) isolado e associado ao valor do lactato no líquor para diferenciar meningite bacteriana (MB) e meningite asséptica (MA). Métodos: Foram selecionadas crianças com meningite atendidas em hospital terciário privado entre janeiro de 2011 e dezembro de 2014. Os dados foram obtidos na admissão. Utilizou-se o EMB com: coloração de Gram no líquor (2 pontos); neutrófilos no líquor ≥1.000 células/mm3 (1 ponto); proteína no líquor ≥80 mg/dL (1 ponto); neutrófilos no sangue periférico ≥10.000 células/mm3 (1 ponto); e convulsão durante/antes da chegada (1 ponto). Analisou-se também o lactato no líquor (elevado: ≥30 mg/dL). Avaliaram-se sensibilidade, especificidade e valor preditivo negativo de diversos valores de corte do EMB e do EMB associado ao lactato elevado para prever MB. Resultados: Dos 439 pacientes elegíveis, 94 não tinham todos os dados necessários para o escore, sendo 345 pacientes selecionados: 7 no grupo de MB e 338 no de MA. Como preditivos de MB, o EMB ≥1 mostrou sensibilidade de 100% (intervalo de confiança de 95% - IC95% 47,3-100), especificidade de 64,2% (58,8-100) e valor preditivo negativo de 100% (97,5-100), enquanto o EMB ≥2 ou EMB ≥1 associado a lactato liquórico ≥30 mg/dL mostrou sensibilidade de 100% (47,3-100), especificidade de 98,5% (96,6-99,5) e valor preditivo negativo de 100% (98,3-100). Conclusões: O EMB com 2 pontos associado à dosagem de lactato no líquor manteve a sensibilidade e o valor preditivo negativo, ao passo que aumentou a especificidade para identificar meningites bacterianas em relação à utilização do EMB com 1 ponto.

ABSTRACT Objective: To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis. Methods: Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis. Results: Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100). Conclusions: 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS.

Comparison of culture and PCR methods in the diagnosis of bacterial meningitis

Abstract Our aim in this study is to compare the standard culture method with the multiplex PCR and the Speed-Oligo® Bacterial Meningitis Test (SO-BMT) – a hybridization-based molecular test method – during the CSF examination of the patients with the pre-diagnosis of acute bacterial meningitis. For the purposes of this study, patients with acute bacterial meningitis treated at the Dicle University Medical Faculty Hospital, Infectious Diseases and Clinical Microbiology Clinic between December 2009 and April 2012 were retrospectively evaluated. The diagnosis of bacterial meningitis was made based on the clinical findings, laboratory test anomalies, CSF analysis results, and the radiological images. Growth was observed in the CSF cultures of 10 out of the 57 patients included in the study (17.5%) and Streptococcus pneumoniae was isolated in all of them. The CSF samples of 34 patients (59.6%) were positive according to the SO-BMT and S. pneumoniae was detected in 33 of the samples (97.05%), while Neisseria meningitidis was found in 1 sample (2.95%). In a total of 10 patients, S. pneumoniae was both isolated in the CSF culture and detected in the SO-BMT. The culture and the SO-BMT were negative in 23 of the CSF samples. There was no sample in which the CSF culture was positive although the SO-BMT was negative. While SO-BMT seems to be a more efficient method than bacterial culturing to determine the pathogens that most commonly cause bacterial meningitis in adults, further studies conducted on larger populations are needed in order to assess its efficiency and uses.

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.

Meningite aguda bacteriana na população infantojuvenil: principais agentes e métodos para diagnóstico - uma revisão da literatura / Acute bacterial meningitis in children and young population: main agents and methods for diagnosis - a literature review

A meningite bacteriana é uma afecção de grande significância devido a sua relação com alta mortalidade e morbidade na população neonatal a jovem. Devido a este fato é importante o conhecimento sobre esta doença e os seus principais agentes etiológicos. Com o objetivo de relatar os principais métodos de diagnóstico, assim como os principais agentes etiológicos envolvidos na fisiopatologia da meningite bacteriana em população jovem foi realizada uma busca por artigos publicados nos últimos 5 anos nas bases de dados Pubmed, Scielo, Bireme e Lilacs. A literatura atual aponta como microrganismos predominantes na incidência dessa doença a N. meningitidis S. pneumoniae, sendo as mais recorrentes na população de faixa etária entre 29 dias e 17 anos. Os fatores relacionados ao prognóstico estão intimamente relacionados com a distinção da classificação do agente etiológico em bacteriano ou viral, importante para a determinação da terapia adequada.

Bacterial meningitis is a highly significant disease due to its relationship with high mortality and morbidity in neonatal and young population. Due to this is important to know about this disease and its main etiological agents. In purpose to report the main diagnostic methods, as well as the main etiological agents involved in the pathophysiology of bacterial meningitis was conducted a search for articles published in the last five years in Pubmed, Scielo, Bireme and Lilacs. The current literature indicates N. meningitidis S. pneumoniae the most predominant microorganisms in the incidence of this disease between population aged between 29 days and 17 years. Factors related to prognosis are closely related to the classification distinction of the etiologic agent in bacterial or viral, important to determine the ap- propriate therapy.

Investigation on the monoclonal antibodies as differential markers for viral and bacterial meningitis by means of immnunohistochemistry technique / Avaliação de anticorpos monoclonais como marcadores diferenciais de meningites bacterianas e virais por meio de técnica imuno-histoquímica

Since 1996, the Laboratory of Monoclonal Antibodies Antigens and Adjuvants - Immunology Center of Adolfo Lutz Institute (IC-IAL) has been working on N. meningitidis strains antigens characterization by using a predetermined monoclonal antibodies (MoAb) panel; and the new monoclonal production has been performed for characterizing strains with unknown profiles. MoAb were obtained from different fusions performed at IAL using spleen cells and popliteal lymph nodes. Two murine hybridomas secreting MoAb anti-N. meningitidis antigens, produced and characterized in the Laboratory of IC-IAL, are presently being evaluated by immunohistochemical (IHC) technique at Immunohistochemistry Laboratory - Pathology Center, IAL. After standardizing these reactions, a protocol for performing investigation on N.meningitidis antigens by using IHQ was established. An increment in the histopathological diagnosis of meningococcal meningitis was occurred, by using MoAb specific for antigens from N. meningitidis serogroups, serotypes and subtypes, mainly in those cases without microorganisms confirmation by biomolecular techniques as PCR. The results obtained in these first tests proved to be promising, and two MoAb showed excellent results. No cross-reactivity with viral meningitis, S. pneumoniae, Rickettsia or Rubella was detected. For the further studies, it is fundamental to increase the samples size, including samples from patients with meningococcal meningitis and from individuals infected with other pathogens.

Desde 1996, o Laboratório de Anticorpos Monoclonais, Antígenos e Adjuvantes - Centro de Imunologia do Instituto Adolfo Lutz (CI-IAL) tem desenvolvido trabalhos na caracterização antigênica de cepas de Neisseria meningitidis utilizando-se painel de anticorpos monoclonais (AcMo) pré-estabelecido, e produção de novos monoclonais para a análise de cepas com perfis desconhecidos. AcMo foram obtidos das diferentes fusões realizadas no laboratório utilizando-se células esplênicas e linfonodos poplíteos. Dois hibridomas murinos secretores de AcMo anti-N. meningitidis produzidos e caracterizados no CI-IAL têm sido avaliados por meio de estudo imuno-histoquímico (IHQ) no Centro de Patologia-Laboratório de Imunohistoquímica-IAL. Com a padronização da reação, estabeleceu-se um protocolo para efetuar a pesquisa de antígenos de N. meningitidis por IHQ. Houve melhoria no diagnóstico histopatológico da meningite meningocócica, sobretudo em situações em que não há confirmação da presença do microorganismo por técnicas biomoleculares, como PCR, utilizando-se AcMo específicos para antígenos de diferentes sorogrupos, sorotipos e subtipos de N. meningitidis. O resultado obtido nos primeiros testes mostrou-se promissor, e os dois AcMo demonstraram excelentes resultados. Não houve reatividade cruzada com meningite viral, S. pneumoniae, Rickettsia ou rubéola. Nos próximos estudos, é fundamental ampliar número de amostras, incluindo-se aquelas coletadas de pacientes com meningites meningocócicas e de indivíduos infectados com outros agentes patogênicos.