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

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±0.3ng/mL in controls, 3.3±1.7ng/mL in viral and 174.8±46.7ng/mL in bacterial meningitis. Mean serum level was 0.84±0.3ng/mL in the controls, 3.7±1.9ng/mL in viral, and 192.2±56.6ng/mL in bacterial meningitis. Both HBP levels were significantly higher in patients with bacterial meningitis. Cut-offs of 56.7ng/ml and 45.3ng/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.

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.

Use of cerebrospinal fluid and serum samples impregnated on FTATM Elute filter paper for the diagnosis of infections caused by Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae.

BACKGROUND: The lack of information regarding the burden of acute bacterial meningitis in Latin America leads to a reduction in the estimated incidence rates of the disease, and impairs public health decisions on the use and follow-up of preventive interventions, particularly, the evaluation of existing vaccination policies. The use of the real-time PCR in diagnostic routine procedures has resulted in a substantial increase in confirmed bacterial meningitis cases. However, in resource-poor countries, these assays are only available in reference laboratories. Sample transportation to these laboratories is a critical constraint, as it requires specialized, high cost courier services. To overcome this barrier we evaluated the use of FTATM Elute filter paper cards for the conservation and processing of samples under normal environmental conditions, as they would be when transported from remote and under-equipped healthcare facilities to the reference centers. A total of 401 samples received in 2015 as part of Sao Paulo's national surveillance for routine diagnosis were selected for this study. METHODS: The sensitivity and specificity of real-time PCR were evaluated using fresh serum and cerebrospinal fluid (CSF) samples processed using our laboratory's standard DNA extraction, and processing the same samples after being dried and stored on FTATM card, and DNA extracted following the manufacturer's instructions. RESULTS: The sensitivities for detection of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from CSF dried and stored on FTATM cards were 98%, 92%, and 100%, respectively, and with serum samples were 73%, 88%, and 100%, respectively. When compared to our laboratory's standard methodology, results showed high concordance, with Kappa index ranges of 0.9877-1.00 for CSF, and 0.8004-1.00 for serum samples. CONCLUSION: The use of FTATM cards for CSF and serum conservation and transport represents a rapid, reliable, and cost-effective alternative that will allow obtaining valuable epidemiological information that would otherwise be lost.

Incorporation of real-time PCR into routine public health surveillance of culture negative bacterial meningitis in São Paulo, Brazil.

Real-time (RT)-PCR increases diagnostic yield for bacterial meningitis and is ideal for incorporation into routine surveillance in a developing country. We validated a multiplex RT-PCR assay for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae in Brazil. Risk factors for being culture-negative, RT-PCR positive were determined. The sensitivity of RT-PCR in cerebrospinal fluid (CSF) was 100% (95% confidence limits, 96.0%-100%) for N. meningitidis, 97.8% (85.5%-99.9%) for S. pneumoniae, and 66.7% (9.4%-99.2%) for H. influenzae. Specificity ranged from 98.9% to 100%. Addition of RT-PCR to routine microbiologic methods increased the yield for detection of S. pneumoniae, N. meningitidis, and H. influenzae cases by 52%, 85%, and 20%, respectively. The main risk factor for being culture negative and RT-PCR positive was presence of antibiotic in CSF (odds ratio 12.2, 95% CI 5.9-25.0). RT-PCR using CSF was highly sensitive and specific and substantially added to measures of meningitis disease burden when incorporated into routine public health surveillance in Brazil.

Serum procalcitonin and other biologic markers to distinguish between bacterial and aseptic meningitis.

OBJECTIVE: To identify the biologic tests that best distinguish between bacterial and aseptic meningitis in an emergency department (ED). STUDY DESIGN: All children hospitalized for bacterial meningitis between 1995 and 2004 or for aseptic meningitis between 2000 and 2004 were included in a retrospective cohort study. Predictive values of blood (C-reactive protein, procalcitonin [PCT], white blood cell [WBC] count, neutrophil count) and cerebrospinal fluid (CSF) findings (protein, glucose, WBC count, neutrophil count) available in the ED were determined. Tests with the best predictive value were identified by using univariate and multivariate analyses and ROC curves comparison. RESULTS: Among the 167 patients included, 21 had bacterial meningitis. The CSF gram-stain and bacterial antigen test had 86% and 60% sensitivity rates, respectively. PCT (>/=0.5 ng/mL) and CSF protein (>/=0.5 g/L) were the best biologic tests, with 89% and 86% sensitivity rates, 89% and 78% specificity rates, adjusted odds ratios of 108 (95% CI, 15-772) and 34 (95% CI, 5-217), and areas under the ROC curves of 0.95 and 0.93, respectively. CONCLUSION: PCT and CSF protein had the best predictive value to distinguish between bacterial and aseptic meningitis in children.

Neonatal sepsis and meningitis in Haiti.

The aim of the study was to determine the etiology of meningitis and sepsis in the newborn at the State University Hospital of Haiti and evaluate the susceptibility 'in vitro' of the pathogens to the antibiotics commonly used. This was a prospective case series study over a 10-month period (May 1997-February 1998) of 42 newborns with sepsis and/or meningitis. Besides the clinical signs, a positive blood culture and/or a positive culture of cerebrospinal fluid was present in each case. Gram-negative bacteria were most commonly found as a cause of early onset sepsis, with Enterobacter aerogenes as the most common agent. There were no such difference between gram-negative and gram-positive in late onset sepsis. Group B Streptococcus was associated with neonatal meningitis (44 per cent of cases) which was more related to gram-positive bacteria (66 per cent). Risk factors were vaginal discharge and dysuria in mothers, and low apgar score in newborns. Thirty-three per cent of the pathogens found, among them Klebsiella pneumoniae, were resistant 'in vitro' to ampicillin and gentamycin. All were susceptible to amikacin. Enterobacter aerogenes is an important pathogen in the etiology of early onset sepsis in the newborn at the State University Hospital of Haiti, while Group B Streptococcus is the leading cause of meningitis in that age group. Resistance to gentamycin should be taken into consideration for the treatment of sepsis and meningitis in the newborn.

Staphylococcus aureus meningitis in children: a review of 30 community-acquired cases

In spite of the steady increase in the incidence of Staphylococcus aureus infections, it remains a relatively uncommon cause of meningitis. To our knowledge, no series of community-acquired S. aureus meningitis (CASAM) restricted to children has been published. So far in this retrospective study we report our experience with CASAM in children, hospitalized from 1983 to 1998 at Nossa Senhora da Glória Children's Hospital (HINSG). During the sixteen-year study period, 2,319 new cases of acute pyogenic meningitis were diagnosed at HINSG. Community-acquired S. aureus was identified as the causative agent in 30 patients (1.3 percent). The predominantly spinal localization of the agent is stressed. In contrast with publications which analyze adults, it has a better prognosis

C-reactive protein is useful in distinguishing Gram stain-negative bacterial meningitis from viral meningitis in children.

OBJECTIVE: To clarify to what extent Gram stain-negative bacterial meningitis can be distinguished from viral meningitis by assessment of cerebrospinal fluid (CSF) and blood indices and serum C-reactive protein (CRP) in children over 3 months of age. DESIGN: Common CSF indices, blood leukocyte counts, and serum CRP values were compared between patients with bacterial meningitis who had a positive CSF bacterial culture but a negative Gram stain and patients with viral meningitis. POPULATION: Three hundred twenty-five consecutive patients with CSF culture-proven bacterial meningitis, for whom Gram stain was negative in 55 cases, and 182 children with proven or presumed viral meningitis. RESULTS: Significant differences between patients with bacterial and viral meningitis were found in all indices with large overlap in all except serum CRP. In patients with bacterial meningitis, the mean CSF glucose concentration, protein concentration, leukocyte count, blood leukocyte count, and serum CRP were 2.9 mmol/L (52 mg/dL), 1.88 g/L, 4540 x 10(6)/L, 18.0 x 10(9)/L, and 115 mg/L; and in those with viral meningitis, mean values were 3.3 mmol/L (59 mg/dL), 0.52 g/L, 240 x 10(6)/L, 10.6 x 10(9)/L, and <20 mg/L, respectively. Of the tests investigated in this study, only serum CRP was capable of distinguishing Gram stain-negative bacterial meningitis from viral meningitis on admission with high sensitivity (96%), high specificity (93%), and high negative predictive value (99%). CONCLUSION: Exclusion of bacterial meningitis with only the conventional tests is difficult. Combined with careful physical examination and CSF analyses, serum CRP measurement affords substantial aid.

[Circulating Haemophilus influenzae in Cuba. Characterization of strains isolated from meningitis]. / Haemophilus influenzae circulantes en Cuba. Caracterización de cepas aisladas de meningitis.

Haemophilus influenzae B(Hib) is often associated with serious systemic infections in children under 5 years of age. Since 1993, it is the most frequent agent isolated in meningoencephalitis. All the strains isolated in the country have been characterized in the National Reference Laboratory at the "Pedro Kourí" Tropical Medicine Institute. Results revealed that 97% of strains isolated from bacterial meningoencephalitis in Cuba during the period 1993-1995 corresponded to serotype B, 0.6% to serotype A and 2.4 not belong to any serotype. The classification of serotype B-strains into biotypes proved that 76% was biotype I and 21% biotype II, 8 to biotype III and 1.2% was biotype V. This study found the following resistance to ampicillin 40%, to chloranphenicol 43.3%, sulpha metoxazol 36%, trimetroprim 37.3% and tetracycline 31%.

[Neonatal bacterial meningitis in a tertiary treatment center]. / Meningitis bacteriana neonatal en una institución de tercer nivel de atención.

OBJECTIVE: To determine incidence, etiologic agents and clinical manifestations of bacterial meningitis in patients hospitalized in the newborn ward at the Hospital Infantil de Mexico in Mexico City and establish the incidence of meningitis in newborns admitted with respiratory distress syndrome (RDS) and determine how often blood cultures are negative in bacterial meningitis in this population. METHODS: Retrospective chart review of patients with bacterial meningitis admitted to our hospital. STUDY PERIOD: January 1990-July 1995. RESULTS: There were 959 admissions to the neonatal intensive care unit (NICU). The overall incidence of bacterial meningitis was 32.3/1000 admissions; however, among 170 patients with RDS, [corrected] meningitis was detected in one (5.9/1000 RDS patients). Of the 31 patients with bacterial meningitis, 10 were preterm (PT) and 21 term (T). In the cerebrospinal fluid (CSF) isolates, there was a predominance of gram negative rods (n: 19; 61%). Clinical findings associated to meningitis were non-specific and there were no differences between PT and T infants. From 31 patients, 19 had negative blood cultures at the time of diagnosis (61%). Mortality associated to bacterial meningitis was [corrected] 40% and 23%, for PT and T, respectively (p = NS). CONCLUSIONS: The incidence of bacterial meningitis in the study population was high. Most isolates in CSF were gram-negative rods. Clinical findings in meningitis were non-specific and there were no differences between PT and T. Most of the patients (61%) had negative blood cultures at the time of diagnosis.

Meningitis bacteriana neonatal en una institución de tercer nivel de atención / Neonatal bacterial meningitis in a third level care unit

Objetivo. Conocer la incidencia, etiología, características clínicas y mortalidad de los pacientes con meningitis neonatal de la unidad de cuidados intensivos neonatales (UCIN) del Hospital Infantil de México Federico Gómez y analizar la incidencia de meningitis en recién nacidos (RN) con síndrome de dificultad respiratoria (SDR); asimismo, determinar la frecuencia de meningitis bacteriana neonatal con hemocultivos negativos. Material y métodos. Revisión retrospectiva de los expedientes clínicos de todos los RN que tenían el dianóstico de meningitis y que fueron admitidos a la UCIN de enero de 1990 a julio de 1995. Se compararon variables entre recién nacidos pretérmino (RNPT) y recién nacidos de término (RNT). Resultados. Se detectaton 31 pacientes (21 RNT y 10 RNPT) con meningitis neonatal (incidencia de 32.2 X 1000 egresos en UCIN); asimismo, se encontró un caso de meningitis neonatal en 170 pacientes con SDR (5.9/1000 RN con SDR). Los gérmenes más frecuentes aislados en LCR fueron bacilos gramnegativos (n: 19;61 por ciento). Los hallazgos clínicos de meningitis fueron inespecíficos no hubo diferencias en RNPT y RNT. Del total de pacientes con meningitis, 19(61 por ciento) tuvieron hemocultivos negativos al momento del diagnóstico. La mortalidad asociada a meningitis en RNPT y RNT fue del 40 y 24 por ciento, respectivamente (P=NS). Conclusiones. La incidencia de meningitis neonatal fue alta. Los gérmenes predominantes en meningitis fueron bacilos gramnegativos. Las manifestaciones clínicas de meningitis fueron inespecíficas y no hubo diferencia entre RNT y RNPT. El 61 por ciento de los pacientes con meningitis tuvo hemocultivos periféricos negativos. Debido a esto, en nuestra población es recomendable realizar la punción lumbar en pacientes con probable sepsis aun con hemocultivo negativo

Variáveis clínicas e laboratoriais para diagnóstico diferencial entre meningites asséptica e piogênica em crianças / Laboratorial and clinical variables to the differential diagnosis between aseptic and pyogenic meningitis in children

Foram estudadas informaçöes obtidas do prontuário de 573 crianças com idade entre 1 mês e 15 anos e diagnóstico de meningite, internadas no Hospital Couto Maia, na cidade de Salvador-Bahia, no período de janeiro-1990 a dezembro-1992. Crises epilépticas, diminuiçäo do nível de consciência e rigidez de nuca foram mais frequentes no grupo com meningite bacteriana. Glicorraquia menor que 45 mg/dL, proteinorraquia igual ou superior a 140 mg/Dl e celularidade liquórica superior a 600 cels/mm3 mostraram-se preditores de meningite piogênica. A análise de curva ROC foi utilizada para estabelecer o melhor ponto de corte nas medidas liquóricas de celularidade, proteínas e glicose capaz de predizer meningite bacteriana. Os resultados encontrados enfatizam que informaçöes clínicas, obtidas com a anamnese e o exame neurológico, e liquóricas simples, definidas pelos níveis de proteína, glicose e análise da celularidade, podem ser utilizadas como medidas de grande acurácia para diferenciar meningite piogênica de asséptica em crianças.

[Laboratory and clinical variables in the differential diagnosis of aseptic and pyogenic meningitis in children]. / Variáveis clínicas e laboratoriais para o diagnóstico diferencial entre meningites Asséptica e piogênica em crianças.

We reviewed the charts of 573 children with a final diagnosis of pyogenic or aseptic meningitis, who were hospitalized in a large reference hospital for the treatment of infectious disease, from January 1990 to December 1992. Seizures, decreased consciousness, nuchal rigidity were more frequent in bacterial than in aseptic meningitis. A cerebrospinal fluid (CSF) glucose level lower than 45 mg/dL, a protein level equal or greater than 140 mg/dL and cell count greater than 600/mm3 were predictors of pyogenic meningitis. Receiver operating characteristic curve analysis was used to assess the best point in CSF measures of leukocytes, glucose and protein that could predict bacterial meningitis. These results suggest that clinicians should differentiate bacterial from aseptic meningitis in children with greater accuracy utilizing only clinical and simple CSF data.

Diagnosis of bacterial meningitis and septicemia by serum counterimmunoelectrophoresis.

We compare the results obtained by counterimmunoelectrophoresis in samples of serum and cerebrospinal fluid with microbiologic methods for 3,298 patients suspected of bacterial meningitis and/or septicemia at Instituto Adolfo Lutz, São Paulo, in a retrospective study of the period from July 1998 to July 1994. Of the 415 patients (12.6% of the total cases studied) who were positive by the serum test, only 249 (7.6% of the total cases studied) were also positive when cerebrospinal fluid was assayed. Thus, 40% of the positives (5.6% of the total) were identifiable by analysis of serum but not of cerebrospinal fluid. Neisseria meningitidis accounted for 77.7% (129) and Haemophilus influenzae for 22.3% (37) of the positive results obtained only when serum was examined. These data show that although sensitivity and specificity of serum counterimmunoelectrophoresis are relatively low compared to cerebrospinal fluid counterimmunoelectrophoresis, the serum test is necessary to complement cerebrospinal fluid counterimmunoelectrophoresis data.

Diagnosis of bacterial meningitis and septicemia by serum counterimmunoelectrophoresis

We compare the results obtained by counterimmunoelectrophoresis in samples of serum and cerebrospinal fluid with microbiologic methods for 3,298 patients suspected of bacterial meningitis and/or septicemia at Instituto Adolfo Lutz, Säo Paulo, in a retrospective study of the period from July 1988 to July 1994. Of the 415 patients (12.6 percent of the total cases studied) who were positive by the serum test, only 249 (7.6 percent of the total cases studied) were also positive when cerebrospinal fluid was assayed. Thus, 40 percent of the positives (5.6 percent of the total) were identifiable by analysis of serum but not of cerebrospinal fluid. Neisseria meningitidis accounted for 77.7 percent (129) and Haemophilus influenzae for 22.3 percent (37) of the positive results obtained only when serum was examined. These...

Comparison of counterimmunoelectrophoresis, latex agglutination and bacterial culture for the diagnosis of bacterial meningitis using urine, serum and cerebrospinal fluid samples.

1. Urine, serum and cerebrospinal fluid (CSF) samples from 98 children with clinical and laboratory diagnosis of bacterial meningitis were evaluated by counterimmunoelectrophoresis (CIE) and latex agglutination (LA) methods and the results compared to those obtained with bacterial cultures of the CSF samples. Antigens of Neisseria meningitidis groups A, B and C, Haemophilus influenzae type b and Streptococcus pneumoniae were determined by both immunological methods. Serum was diluted (1:4) with 0.1 M sodium EDTA, pH 7.5, and held at 80 degrees C for 10 min before assay. Polysaccharide of the urine samples was precipitated overnight using an equal volume of 1:1 ethanol-acetone followed by a heat-treatment with 0.1 M sodium EDTA, pH 7.5, at 80 degrees C for 10 min.. 2. Sensitivity indices were 0.772 (CSF), 0.595 (urine) and 0.317 (serum) for CIE, and 0.914 (CSF), 0.930 (urine) and 0.683 (serum) for LA in relation to the 42 positive bacterial cultures. 3. The optimal diagnostic efficacy reached 52% for CIE and 72% for LA when urine was concentrated 20- to 30-fold. 4. These data show that immunological tests of urine samples were more effective than bacterial culture for diagnosing bacterial meningitis and may be indicated when negative results are obtained for CSF tested by bacterial culture and immunoassay methods.

Serum C-reactive protein in childhood meningitis in countries with limited laboratory resources: a Chilean experience.

Quantitative C-reactive protein (CRP) was determined sequentially by nephelometry and photometry from a finger prick serum sample in 67 children with bacterial meningitis (BM) and 16 children with aseptic meningitis (AM). The initial mean CRP value of 180 mg/liter in children with BM differed significantly from the 12 mg/liter found in those with AM (P less than 0.001). In BM a slow descent instead of rapid normalization or a secondary increase in sequential CRP values were early indicators of complications during recovery, such as resistance to the antibiotic. A significant difference in the mean CRP values between uneventful and complicated courses of BM was observed from the fourth day on (P less than 0.001). The measurements obtained with nephelometry correlated reliably with the more widely available photometry (r = 0.99). Easily performed rapid CRP determinations can considerably improve the quality of care in meningitis patients, especially in those situations where facilities for performing bacterial cultures or antibiotic susceptibility testing are not available.