Acute meningitis prognosis using cerebrospinal fluid interleukin-6 levels.

BACKGROUND: Improved diagnostic tests would aid in diagnosing and treating community-acquired meningitis. OBJECTIVE: To analyze the diagnostic value of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients presenting with symptoms of acute meningitis. MATERIAL AND METHODS: In a 6-month prospective, observational, cross-sectional emergency department (ED) study, serum and CSF samples were obtained from all patients with a headache and fever in whom the physician suspected meningitis. Patients were excluded if computed tomography findings contraindicated a lumbar puncture, if they had bleeding disorders, or if their serum indicated bleeding. IL-6 levels were measured and compared in patients with (Group A) and without (Group B) bacterial meningitis. RESULTS: Samples were obtained from 53 patients, of whom 40 were ultimately found to have meningitis. These 40 patients averaged 49.6 ± 21.9 years, with number of men 18 (45%), hospitalizations 21 (52%), mortality 3 (.07%), and IL-6 average rating 491 (median: 14.5; range 0000-6000). Findings in the two groups were: Group A (with meningitis): n = 13, average IL-6 level: 1495 (median: 604; 25/75 percentiles: 232.5-2030; 95% confidence interval [CI] 371.7-2618.6; range 64-6000). Group B (with aseptic meningitis): n = 27, average IL-6 level: 7.34 (median: 5; 25/75 percentiles: 0.0/15.1; 95% CI 3.94-10.73; range 0-23.6). Mann-Whitney rank sum test: p < 0.0001. CONCLUSIONS: In patients with acute bacterial meningitis, CSF cytokine concentrations are elevated. Measuring CSF inflammatory cytokine levels in patients with acute meningitis could be a valuable ED diagnostic tool. Using this tool could improve the prognosis of patients with bacterial meningitis by allowing more rapid initiation of antibiotic treatment.

Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H. influenzae type b in Brazil.

Following routine childhood vaccination against Haemophilus influenzae type b (Hib) disease in Brazil in 1999, passive laboratory surveillance reported increasing numbers of non-b serotypes and nontypeable H. influenzae (NTHi) from meningitis cases. To characterize this increase, we analyzed data on 3910 H. influenzae isolated from cerebrospinal fluid or blood from meningitis cases that were sent to the national reference laboratory for serotyping from 1990 to 2008. Hib accounted for 98% of H. influenzae meningitis isolates received during 1990-1999 versus 59% during 2000-2008, while non-b serotypes increased from 1% to 19% and NTHi increased from 2% to 22% of H. influenzae isolates received during the two periods. Higher proportions of non-b serotypes and NTHi than Hib were isolated from blood rather than cerebrospinal fluid. Estimated incidence rates for H. influenzae meningitis for Sao Paulo state remained below 1 case per million population during 2000-2008, although annual incidence of NTHi meningitis (mean, 0.03 cases per 100,000 population) increased in several age groups. Changes in surveillance for H. influenzae following introduction of Hib conjugate vaccine likely contributed to increased numbers of non-b and nontypeable H. influenzae meningitis isolates received at the national reference laboratory.

Haemophilus influenzae serotype a meningitis.

This work describes a case of Haemophilus influenzae serotype a meningitis in Brazil, after almost a decade since the introduction of Haemophilus influenzae serotype b conjugate vaccine. Uncertainty about the replacement of H. influenzae serotypes as a cause of invasive diseases justifies continuous surveillance, coupled with investigations of carriage rates and requirements of chemoprophylaxis in contact persons.

Microbial genome count in cerebrospinal fluid compared with clinical characteristics in pneumococcal and Haemophilus influenzae type b meningitis in children.

Cerebrospinal fluid genome counts were determined by quantitative real-time polymerase chain reaction from 121 children: 36 with Streptococcus pneumoniae and 85 with Haemophilus influenzae meningitis. To examine the interactions of genome count and to determine its prognostic importance, we projected the results against findings on admission and different outcomes. The genome count varied vastly in both meningitides ranging from 0 to 9,250,000/microL. The genome quantity was weakly associated with only some of the patient findings on admission. High counts predicted neurologic (odds ratio [OR]=1.36; 95% confidence interval [CI], 1.09-1.69; P=0.006 for 1 log increase) but not audiologic sequelae. They also predicted death in S .pneumoniae (OR=2.05; 95% CI, 1.08-3.87; P=0.03) but not in H. influenzae meningitis.

[Multiplex PCR assay in spinal fluid to identify simultaneously bacterial pathogens associated to acute bacterial meningitis in Chilean children]. / Diseño y evaluación de una reacción de polimerasa en cadena (RPC) múltiple, para la identificación de bacterias causantes de meningitis aguda en líquido cefalorraquídeo de niños chilenos.

BACKGROUND: Acute bacterial meningitis (ABM) is a serious disease that needs rapid diagnosis for an accurate treatment. The most important etiological agents are: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b. Overall pathogen detection rate in patients with ABM in Chile is 83%. AIM: To evaluate a Polymerase Chain Reaction (PCR) protocol for simultaneous detection of several pathogens in patients with ABM. MATERIAL AND METHODS: We designed and evaluated a multiplex PCR protocol for simultaneous specific genes identifications of S pneumoniae ( inverted exclamation markytA and ply genes), N meningitidis (ctrA, crgA) and H influenzae (bexA) in cerebrospinal fluid (CSF) samples from pediatric patients with suspected diagnosis of ABM. Sensitivity, specificity and minimum detection levels of DNA were determined. Amplifications ofrDNA 16S gene was done to confirm extraction of bacterial DNA. RESULTS: Ninety nine CSF samples were studied, 90 from children with fever and negative CSF culture, and 9 from ABM and positive culture patients. The PCR protocol had a sensitivity of 89%, specificity of 100%, positive predictive value 100% and negative predictive value 99%. CONCLUSIONS: We observed a high concordance (89%) between bacteriological cultures and the PCR protocol results. This diagnostic tool could increase identification of agents in specific settings such as patients previously treated with antibiotics.

Diseño y evaluación de una reacción de polimerasa en cadena (RPC) múltiple, para la identificación de bacterias causantes de meningitis aguda en líquido cefalorraquídeo de niños chilenos / Multiplex PCR assay in spinal fluid to identify simultaneously bacterial pathogens associated to acute bacterial meningitis in Chilean children

Background: Acute bacterial meningitis (ABM) is a serious disease that needs rapid diagnosis for an accurate treatment. The most important etiological agents are: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b. Overall pathogen detection rate in patients with ABM in Chile is 83 percent. Aim: To evaluate a Polymerase Chain Reaction (PCR) protocol for simultaneous detection of several pathogens in patients with ABM. Material and methods: We designed and evaluated a multiplex PCR protocol for simultaneous specific genes identifications of S pneumoniae (¡ytA and ply genes), N meningitidis (ctrA, crgA) and H influenzae (bexA) in cerebrospinal fluid (CSF) samples from pediatric patients with suspected diagnosis of ABM. Sensitivity, specificity and minimum detection levels of DNA were determined. Amplifications ofrDNA 16S gene was done to confirm extraction of bacterial DNA. Results: Ninety nine CSF samples were studied, 90 from children with fever and negative CSF culture, and 9 from ABM and positive culture patients. The PCR protocol had a sensitivity of 89 percent, specificity of 100 percent, positive predictive value 100 percent and negative predictive value 99 percent. Conclusions: We observed a high concordance (89 percent) between bacteriological cultures and the PCR protocol results. This diagnostic tool could increase identification of agents in specific settings such as patients previously treated with antibiotics.

[Acute meningitis in Córdoba, Colombia (2002-2004)]. / Meningitis agudas en Córdoba, Colombia 2002-2004.

OBJECTIVE: Establishing characteristic epidemiologic and microbiologic features of acute meningitis in the Córdoba department. METHODOLOGY: A descriptive epidemiological study was carried out between June 2002 and June 2004 at the Hospital San Jerónimo in Montería. All suspicious cases of meningitis were included; laboratory tests included cytological smear, biochemistry, latex, Gram stain and culture. RESULTS: 57 (11.3%) and 85 (16.8%) of the 503 samples of cerebrum spinal fluid (CSF) were confirmed by culture as being probable cases. There were 6 cases of polymicrobial infection, making a total of 63 isolates: 17 non-fermenting Gram-negative bacilli (26.9%), 16 Streptococcus pneumoniae (25.4%), 7 Enterobacteriaceae (11%), 5 Criptococcus neoformans (8%) 4 Neisseria meningitidis serotype B (6.3%), 3 S. viridans (4.8%), 2 Streptococcus group B (3.2%), 2 Haemophilus influenzae type B (3.2%), 2 Staphylococcus negative coagulase (3.2%), 2 S. aureus (3.2%), 2 Enterococcus (3.2%) and 1 Candida albicans (1.6%). The S. Pneumoniae serotypes found were: 5 (n=4), 23F (n=3), 14 (n=2), 18C (n=2), 18A (n=l1, 17F (n=l1, 1 (n=1). CONCLUSIONS: The study led to determining epidemiological and microbiological aspects of acute meningitis in the Códoba department which had been unknown up to now. Streptococcus pneumoniae (25.4% was the main aetiological agent of meningitis; the epidemiologic aspects so established confirmed the need for strengthening and implementing measures for controlling meningitis in C6ódoba and its surveillance there.

Meningitis Agudas en Córdoba, Colombia 2002 - 2004 / Acute meningitis in Córdoba, Colombia (2002-2004)

Objetivo: Establecer las características epidemiológicas y microbiológicas de las meningitis agudas del departamento de Córdoba. Métodos: Se realizó un estudio descriptivo de vigilancia epidemiológica en el Hospital San Jerónimo de Montería. Se tomaron todos los casos de meningitis, presentados (junio 2002 - junio 2004), las pruebas de laboratorio incluyeron: citoquímico, prueba de látex, tinción de Gram y cultivo. Resultados: Se analizaron 503 muestras de liquido cefalorraquídeo, confirmados por cultivo 57 (11,3 por ciento) casos y 85 (16,8 por ciento) casos probables. Se presentaron 63 aislamientos distribuidos así: 17 bacilos Gram negativos no fermentadores (26,9 por ciento), 16 Streptococcus pneumoniae (25,4 por ciento), 7 Enterobacterias (1 por ciento), 5 Criptococcus neoformans (8 por ciento), 4 Neisseria meningitidis serotipo B (6,3 por ciento), 3 S. viridans (4,8 por ciento), 2 Streptococcus grupo B (3,2 por ciento), 2 Haemophilus influenzae tipo B (3,2 por ciento), 2 S. aureus (3,2 por ciento), 2 Staphylococcus coagulasa negativos (3,2 por ciento), 2 Enterococcus (3,2 por ciento) y 1 Candida albicans (1,6 por ciento). Los serotipos de S. Pneumoniae fueron: 5 (n=4), 23F (n=3), 14 (n=2), 18C (n=2), 18A (n=1), 17F (n=1), 1 (n=1). Conclusión: El estudio permitió determinar los aspectos epidemiológicos y microbiológicos hasta ahora desconocidos de las meningitis agudas en el departamento de Córdoba. Streptococcus pneumoniae (25,4 por ciento) fue el principal agente causal de meningitis, los aspectos epidemiológicos establecidos confirman la necesidad de fortalecer e implantar medidas para el control y vigilancia de las meningitis en Córdoba.

Latex particle agglutination test in the diagnosis of Haemophilus influenzae type B, Streptococcus pneumoniae and Neisseria meningitidis A and C meningitis in infants and children.

The knowledge of purulent meningitis etiology is essential in deciding the immediate therapy; in developing countries, however, the etiological agent identification does not reach 60% of the cases. A comparative study using the latex particle agglutination test (LPAT) in cerebrospinal fluid (CSF) for the diagnosis of meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae or Neisseria meningitidis A and C was carried out in Belo Horizonte MG, Brazil. CSF culture was used as a gold-standard. Two hundred and ninety-nine children, ranging from 3 months to 14 years of age, were included in the investigation. One hundred and forty-four presented a positive CSF culture for the above mentioned bacteria; the remaining presented meningitis due to other organisms (other bacteria or viral) or a normal CSF. The sensitivity and the specificity of LPAT was 95.7 and 100.0% for N. meningitidis C, 95.2 and 100.0% for H. influenzae type b and 86.5 and 100.0% for S. pneumoniae, respectively. When all three organisms were considered simultaneously, the sensitivity and the specificity was 93.0 and 100.0%, respectively. Taking into consideration a realistic estimate of disease prevalence in the community where the diagnostic test is being used, the positive predictive value and the posttest probability were estimated as 36.7 and 47.1% for children < 5 years and as 21.3 and 35.1% for children < 14 years of age, respectively. LPAT is a useful diagnostic test for meningitis due to the studied pathogens, especially in developing countries where laboratory facilities are limited.

Aspectos dos líquidos cefalorraquidianos nas meningites bacterianas / The cerebrospinal fluid in bacterial meningitis

Samples of 1815 cerebrospinal fluid (CSF) were studied in a meningitis outbreak during 1989 in S ao Paulo, Brazil. Neisseria meningitis 56 per cent with 44 per cent type B, Haemophilus influenzae 17 per cent , from which 72 per cent in children (days to 3-year-old) and Streptococcus pneumoniae 14 per cent from which 60 per cent in children (day to 1-year-old) of 443 (24 per cent ) of all strains. Cytochemistry study showed: purulent or turbidity aspects in 70 to 79 per cent positive bacterioscopy or culture of CSF; white cells count > 500/mm3; glucose < 45 mg/dl; protein > 90 mg/dl in 90 per cent of all patients. We concluded that: CSF prognostic factors: (aspect and cytochemistry) were correlated with bacterial meningitis. Bacterioscopy and positive cultures were correlated to NM, SP and HI isolation from these patients (Goodman Test)

[The cerebrospinal fluid in bacterial meningitis]. / Aspectos dos líquidos cefalorraquidianos nas meningites bacterianas.

Samples of 1815 cerebrospinal fluid (CSF) were studied in a meningitis outbreak during 1989 in São Paulo, Brazil. Neisseria meningitis 56% with 44% type B, Haemophilus influenzae 17%, from which 72% in children (days to 3-year-old) and Streptococcus pneumoniae 14% from which 60% in children (day to 1-year-old) of 443 (24%) of all strains. Cytochemistry study showed: purulent or turbidity aspects in 70 to 79% positive bacterioscopy or culture of CSF; white cells count > 500/mm3; glucose < 45 mg/dl; protein > 90 mg/dl in 90% of all patients. We concluded that: CSF prognostic factors: (aspect and cytochemistry) were correlated with bacterial meningitis. Bacterioscopy and positive cultures were correlated to NM, SP and HI isolation from these patients (Goodman Test).

Contraimunoeletroforese no diagnóstico etiológico das meningites bacterianas / Counterimmunoelectrophoresis on etiological diagnosis of bacterial meningitis

Contraimunoeletroforese (CIE) tem sido utilizada para o diagnóstico etiológico de meningites bacterianas, através da detecçäo de antígenos polisacarídicos capsulares no líquido cefalorraquiano. O material é composto por 340 exames de amostras de LCR de 292 pacientes, 171 do sexo masculino e 121 do sexo feminino com idade entre 4 dias e 74 anos. Sendo 91 pacientes com perturbaçöes neurológicas diversas e 146 pacientes com diversas formas de meningites sépticas nas quais o agente etiológico foi identificado pelo exame bacterioscópico direto e provas culturais e 55 casos de meningites sépticas em que o agente etiológico näo foi identificado; em 25 pacientes foram feitos exames em 2 amostras; em 10, em 3 amostras e em 1, em 4 amostras. A primeira amostra foi sempre colhida antes da antibioticoterapia e as seguintes após o início da terapêutica. Este material foi dividido em grupos, para se verificar a especificidade e a sensibilidade da contraimunoeletroforese para Haemophilus influenzae tipo B, Neisseria meningitidis A, B e C e Streptococcus pneumoniae (83 sorotipos). A especificidade da contraimunoeletroforese para o Haemophilus influenzae é de 98, 49 e a sensibilidade é de 94,8%. Para o Neisseria meningitidis a especificidade éde 98,58% e a sensibilidade é de 44,4% e, para o Streptococcus pneumoniae a especificidade éde 93,55% e sensibilidade é de 41,1%.

Doença grave, diagnóstico precoce: meningite purulenta e teste de aglutinaçäo de partículas de látex / Grave disease, early diagnosis: bacterial meningitis and latex fixation tests

Desenvolveu-se um estudo transversal controlado prospectivo com o objetivo de avaliar, de forma independente e "cega" e em três etapas distintas e complementares, o desempenho do teste de aglutinaçäo de partículas de látex no diagnóstico etiológico das meningites determinadas pelo H. influenzae b, S. pneumoniae e N. meningitidis A e C em 284 crianças (casos e controles) com idade compreendida entre 3 meses e 14 anos. Na primeira, o teste em estudo foi comparado com um padräo ouro e revelou sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e acurácia equivalentes a 92,7 por cento, 100,0 por cento, 95,0 por cento e 96,9 por cento, respectivamente. Na segunda estabeleceu-de uma comparaçäo com o exame quimiocitológico liquórico, quando entäo a sensibilidade, o valor preditivo negativo e a acurácia reduziram para 63,3 por cento, 70,8 por cento e 80,6 por cento, mantendo-se inalteradas as proporçöes da especificidade do valor preditivo positivo. Na última etapa, associou-se ao teste em estudo à bacterioscopia direta pelo Gram, confrontando-se ambos os métodos, com a cultura e contraimunoeletroforese, visando verificar o comportamento de cada dupla de exames no diagnóstico etiológico, independente do microorganismo causal. Näo ocorreu diferença estatisticamente significante na performance de cada uma dessas duplas de métodos laboratoriais (p=.79). Considerando que além do desempenho observado nesta investigaçäo, o teste em estudo reune outras vantagens como rapidez no fornecimento dos resultados e simplicidade de execuçäo e interpretaçäo, conclui-se que o mesmo representa um instrumento diagnóstico valioso tanto do ponto de vista clínico-individual como em programas de saúde coletiva.

Quantitative levels of C-reactive protein in cerebrospinal fluid in patients with bacterial meningitis and other conditions.

We measured levels of C-reactive protein (CRP) in the cerebrospinal fluid in 145 children, using a solid-phase radioimmunoassay. The CRP levels in 49 patients with culture-proved bacterial meningitis ranged from 0 to 51,000 ng/ml (median 1460 ng/ml). In 33 patients with aseptic meningitis, values were much lower range 0 to 438 ng/ml; (median 17 ng/ml). In patients with CSF pleocytosis (greater than 10 WBC/microliter), CRP greater than 100 ng/ml was 95% accurate in identifying those with bacterial meningitis. However, a few patients with bacterial meningitis and little or no CSF pleocytosis had low levels of CRP at admission. Among the 63 patients with nonmeningitic conditions, those with bacterial infections frequently (10 of 13 had CRP greater than 100 ng/ml, whereas CRP elevations were infrequent (seven (18%) of 40) in patients with viral infections and other conditions. CRP diffuses into the CSF as readily as other proteins, but in bacterial meningitis the CSF/serum ratio of CRP was lower than that of albumin and IgG. The measurement of CRP in CSF is potentially a very useful diagnostic tool, but certain inherent limitations must be recognized, because some patients may fail to mount a prompt inflammatory response.

Moxalactam therapy of Haemophilus influenzae type b meningitis in children.

Thirty-four children with Haemophilus influenzae type b meningitis were given prospectively either moxalactam (200 mg/kg/day) or ampicillin (400 mg/kg/day) plus chloramphenicol (75 mg/kg/day). One patient in each group died. The mean duration of fever, clinical response, sequential cerebrospinal fluid findings, and incidence of neurologic sequelae were similar between groups. Moxalactam cerebrospinal fluid bioactivity was significantly greater than that of ampicillin or chloramphenicol throughout therapy. Neutropenia, liver enzyme abnormalities, and diarrhea were not significantly different. In eight of 11 patients given moxalactam (versus one of 14 controls) there was complete elimination of gram-negative aerobic flora in the stools by day 10 (P = 0.002); however, none acquired Clostridium difficile. Moxalactam in effective therapy for H. influenzae type b meningitis.

Prospective comparative trial of moxalactam versus ampicillin or chloramphenicol for treatment of Haemophilus influenzae type b meningitis in children.

In a prospective, randomized study, moxalactam in 44 children was compared with ampicillin or chloramphenicol in 47 children for the treatment of Haemophilus influenzae type b meningitis. Both groups were comparable in terms of clinical and laboratory findings at admission. The hospital course, neurologic sequelae including deafness, and number of deaths were the same for both groups. The incidence of adverse reactions also was the same except that diarrhea and thrombocytosis occurred significantly (P less than or equal to 0.04) more frequently in children given moxalactam. Moxalactam was equivalent to ampicillin or chloramphenicol in the treatment of H. influenzae type b meningitis in children.

Relation of concentrations of Haemophilus influenzae type b in cerebrospinal fluid to late sequelae of patients with meningitis.

Forty-four patients with Haemophilus influenzae type b meningitis had follow-up evaluations approximately one year after hospital discharge. Patients with greater than or equal to 10(7) colony-forming units of H. influenzae type b per milliliters CSF had significantly greater frequencies of speech impairment (P less than 0.001), hearing loss (P = 0.04), and moderate or severe neurologic sequelae (P less than 0.01). Patients with greater than or equal to 1 microgram H. influenzae b antigen/ml CSF had a greater incidence of hearing loss (P = 0.03) but not of speech abnormalities (P = 0.06) or other neurologic sequelae (P = 0.64). Glucose concentrations less than 10 mg/dl correlated with the incidence of hearing loss (P = 0.02) and speech impairment (P = 0.02). "Partial" antibiotic therapy, CSF protein concentrations, and number of CSF polymorphonuclear leukocytes did not correlate well with sequelae. These data indicate that pretreatment concentrations of H. influenzae b and glucose concentrations in CSF were the best predictors of late sequelae of patients with H. influenzae b meningitis.