Bacterial Meningitis Patients Research Articles

OL-060 In vitro activity of antibiotics on biofilm producing isolates of Pseudomonas aeruginosa

Background: To evaluate the penicillin-binding protein 2B gene (pbp2b) based PCR and sequencing for screening Streptococcus pneumoniae infection and predict its susceptibility in cerebral spinal fluid from paediatric bacterial meningitis patients. Methods: A nested PCR targeting pbp2b and another two S. pneumoniae specific PCR targeting pneumolysin (ply) and autolysin (lytA) were developed for detection of S. pneumoniae in cerebral spinal fluid from bacterial meningitis patients. The PCR results of three different genes and culture were compared. The consistency of penicillin susceptibility PCR (using resistant and susceptible primers respectively), sequencing and culture based phenotypic penicillin resistant results were compared. Result: Of the 161 specimens studied, there were totally 25 S. pneumoniae infection confirmed by different methods (16 by lytA PCR, 14 by ply PCR, 16 by pbp2b PCR and 9 by cerebrospinal fluid culture). Of the 16 pbp2b positive specimens, penicillin sensitive and resistant sequence types account for half respectively. 4 of the 16 pbp2b positive specimens had culture based phenotypic penicillin-resistant result. 3 of 4 were consistent with penicillin susceptibility PCR result. The result of susceptibility PCR targeting pbp2b was consistent with sequencing result. There were no new point mutations but new sequence types were found in these strains when compared with GenBank. Penicillin resistant in pneumococcal meningitis was 66.67% (6/9) by culture phenotype and 50% (8/16) by PCR and sequencing when culture was negative. Conclusion: pbp2b can be served as a good target gene to detect S. pneumoniae and predict its penicillin susceptibility, especially important when culture was negative.

OL-059 Penicillin-binding protein 2B gene (pbp2b) based PCR and sequencing for screening Streptococcus pneumoniae infection and predicting its susceptibility in cerebral spinal fluid from paediatric bacterial meningitis patients

OL-059 Penicillin-binding protein 2B gene (pbp2b) based PCR and sequencing for screening Streptococcus pneumoniae infection and predicting its susceptibility in cerebral spinal fluid from paediatric bacterial meningitis patients

SNPs in DNA repair genes associated to meningitis and host immune response

In vitro and in animal models, APE1, OGG1, and PARP-1 have been proposed as being involved with inflammatory response. In this work, we have investigated if the SNPs APE1 Asn148Glu, OGG1 Ser326Cys, and PARP-1 Val762Ala are associated to meningitis. The patient genotypes were investigated by PIRA-PCR or PCR-RFLP. DNA damages were detected in genomic DNA by Fpg treatment. IgG and IgA were measured from plasma and the cytokines and chemokines were measured from cerebrospinal fluid samples using Bio-Plex assays. A higher frequency ( P < 0.05) of APE1 Glu allele in bacterial meningitis (BM) and aseptic meningitis (AM) patients was observed. The genotypes Asn/Asn in control group and Asn/Glu in BM group was also higher. For the SNP OGG1 Ser326Cys, the genotype Cys/Cys was more frequent ( P < 0.05) in BM group. The frequency of PARP-1 Val/Val genotype was higher in control group ( P < 0.05). The occurrence of combined SNPs is significantly higher in BM patients, indicating that these SNPs may be associated to the disease. Increasing in sensitive sites to Fpg was observed in carriers of APE1 Glu allele or OGG1 Cys allele, suggesting that SNPs affect DNA repair activity. Alterations in IgG production were observed in the presence of SNPs APE1 Asn148Glu, OGG1 Ser326Cys or PARP-1 Val762Ala. Moreover, reduction in the levels of IL-6, IL-1Ra, MCP-1/CCL2 and IL-8/CXCL8 was observed in the presence of APE1 Glu allele in BM patients. In conclusion, we obtained indications of an effect of SNPs in DNA repair genes on the regulation of immune response in meningitis.

Neurointensive care of patients with severe community-acquired meningitis

Reports about neurointensive care of severe community-acquired meningitis are few. The aims of this retrospective study were to review the acute clinical course, management and outcome in a series of bacterial meningitis patients receiving neurointensive care. Thirty patients (median age 51, range 1-81) admitted from a population of 2 million people during 7 years were studied. The neurointensive care protocol included escalated stepwise treatment with mild hyperventilation, cerebrospinal fluid (CSF) drainage, continuous thiopentotal infusion and decompressive craniectomy. Clinical outcome was assessed using the Glasgow outcome scale. Twenty-eight patients did not respond to commands on arrival, five were non-reacting and five had dilated pupils. Twenty-two patients had positive CSF cultures: Streptococcus pneumoniae (n=18), Neisseria meningitidis (n=2), β-streptococcus group A (n=1) and Staphylococcus aureus (n=1). Thirty-five patients were mechanically ventilated. Intracranial pressure (ICP) was monitored in 28 patients (intraventricular catheter=26, intracerebral transducers=2). CSF was drained in 15 patients. Three patients received thiopentothal. Increased ICP (>20 mmHg) was observed in 7/26 patients with available ICP data. Six patients died during neurointensive care: total brain infarction (n=4), cardiac arrest (n=1) and treatment withdrawal (n=1). Seven patients died after discharge, three due to meningitis complications. At follow-up, 14 patients showed good recovery, six moderate disability, two severe disability and 13 were dead. Patients judged to have severe meningitis should be admitted to neurointensive care units without delay for ICP monitoring and management according to modern neurointensive care principles.

Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis

BackgroundThe kynurenine (KYN) pathway has been shown to be altered in several diseases which compromise the central nervous system (CNS) including infectious diseases such as bacterial meningitis (BM). The aim of this study was to assess single nucleotide polymorphisms (SNPs) in four genes of KYN pathway in patients with meningitis and their correlation with markers of immune response in BM.MethodsOne hundred and one individuals were enrolled in this study to investigate SNPs in the following genes: indoleamine-2,3-dioxygenase (IDO1 gene), kynureninase (KYNU gene), kynurenine aminotransferase I (CCBL1 gene), and kynurenine aminotransferase II (AADAT gene). SNP analyses were performed by primer-introduced restriction analysis-PCR (PIRA-PCR) followed by RFLP. Cytokines were measured using multiplex bead assay while immunoglobulins (IG) by immunodiffusion plates and NF-kappaB and c-Jun by dot blot assay.ResultsThe variant allele of SNP AADAT+401C/T showed prevalent frequency in patients with BM. A significant decrease (p < 0.05) in TNF-α, IL-1β, IL-6, MIP-1αCCL3 and MIP-1β/CCL4 levels was observed in BM patients homozygous (TT) to the SNP AADAT+401C/T. Furthermore, a significant (p < 0.05) decrease in cell count was observed in cerebrospinal fluid (CSF) from patients with TT genotype. In addition, an increase in the IgG level in adults (p < 0.05) was observed. The variant allele for KYNU+715G/A was found with low frequency in the groups, and the SNPs in IDO1+434T/G, KYNU+693G/A, CCBL1+164T/C, and AADAT+650C/T had no frequency in this population.ConclusionsThis study is the first report of an association of SNP AADAT+401C/T with the host immune response to BM, suggesting that this SNP may affect the host ability in recruitment of leukocytes to the infection site. This finding may contribute to identifying potential targets for pharmacological intervention as adjuvant therapy for BM.

Bacterial Meningitis andHaemophilus influenzaeType b Conjugate Vaccine, Malawi

A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997–2009), and pneumococcus was the most common etiologic agent (57% in 2009).

Clinical Features and Outcome of Community-Acquired Bacterial Meningitis in Adult Patients With Liver Cirrhosis

IntroductionThis study aimed to analyze the clinical features, causative pathogens and therapeutic outcomes of bacterial meningitis in patients with liver cirrhosis. MethodsAdult cirrhotic patients with community-acquired bacterial meningitis were evaluated. Clinical data were collected over a 22-year period. For comparison, the clinical features and therapeutic outcomes between patients with and without liver cirrhosis were analyzed. ResultsLiver cirrhosis accounted for 11% (25/217) of the predisposing factors. Significant statistical analysis between the 2 groups (patients with and without liver cirrhosis) included median Glasgow Coma Scale score at presentation, presence of seizure, bacteremia and septic shock. The mean duration between arrival at the emergency room and confirmed diagnosis of bacterial meningitis was 39hours (range, 2–240hours). Ten (10/25, 40%) were initially diagnosed with bacterial meningitis, and 6 (6/25, 24%) were initially suggested as having infection of unknown origin. In this study, Klebsiella pneumoniae was the most frequent causative pathogen in patients with liver cirrhosis. The overall case fatality rates for patients with and without liver cirrhosis were 38.5% (74/192) and 64% (16/25), respectively. ConclusionsPatients with liver cirrhosis have a more fulminant course with a higher prevalence of disturbed consciousness, bacteremia, seizure and shock. Diagnosis and effective treatment ARE often delayed, resulting in high overall mortality. When patients with liver cirrhosis develop disturbed consciousness, seizures and septicemia, immediate neuroimaging and cerebrospinal fluid studies should be undertaken to determine bacterial meningitis. Early diagnosis and treatment are essential for survival.

Bacterial Meningitis in Cirrhotic Patients

To analyze the mortality risk factors in cirrhotic patients with bacterial meningitis (BM). Cirrhotic patients are susceptible to infections. Despite its high mortality rate, BM has not been extensively studied in this group of patients. BM patients diagnosed with cirrhosis, between 1987 and 2008, were studied. BM was defined as the presence of signs or symptoms of meningitis and a cerebrospinal fluid (CSF) leukocyte count >100/mm3 or the presence of bacteria in CSF. We identified 4955 infections among 7591 cirrhotic patients; 12 (0.2%) had BM. The mean age at diagnosis was 60±16 years. Abnormal mental status (83%), fever (67%), and neck stiffness (67%) were the most frequent clinical presentations. The sensitivity of CSF culture was 75% (Streptococcus pneumoniae, 2; Staphylococcus aureus, 2; Listeria monocytogenes, 1; Group B Streptococcus, 1; Streptococcus agalactiae, 1; Streptococcus bovis, 1; and Escherichia coli, 1), and its correlation with blood culture was 78%. Five patients died. On admission, the serum creatinine level was 1.63±0.93 mg/dL. A serum creatinine level ≥1.3 mg/dL was associated with increased mortality (P=0.028). The model for end-stage liver disease score, gastrointestinal bleeding, bilirubin level >3.5 mg/dL, hepatic encephalopathy, diabetes mellitus, and results of cytology and biochemistry tests of CSF were not associated with mortality. BM in cirrhotic patients is associated with a high mortality rate. The clinical and microbiologic features of BM in cirrhotic patients differ from those in the general population. A serum creatinine level ≥1.3 mg/dL on admission is associated with a higher risk of mortality.

Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data

SummaryBackgroundDexamethasone improves outcome for some patients with bacterial meningitis, but not others. We aimed to identify which patients are most likely to benefit from dexamethasone treatment.MethodsWe did a meta-analysis of individual patient data from the randomised, double-blind, placebo-controlled trials of dexamethasone for bacterial meningitis in patients of all ages for which raw data were available. The pre-determined outcome measures were death at the time of first follow-up, death or severe neurological sequelae at 1 month follow-up, death or any neurological sequelae at first follow-up, and death or severe bilateral hearing loss at first follow-up. Combined odds ratios (ORs) and tests for heterogeneity were calculated using conventional Mantel-Haenszel statistics. We also did exploratory analysis of hearing loss among survivors and other exploratory subgroup analyses by use of logistic regression.FindingsData from 2029 patients from five trials were included in the analysis (833 [41·0%] aged <15 years). HIV infection was confirmed or likely in 580 (28·6%) patients and bacterial meningitis was confirmed in 1639 (80·8%). Dexamethasone was not associated with a significant reduction in death (270 of 1019 [26·5%] on dexamethasone vs 275 of 1010 [27·2%] on placebo; OR 0·97, 95% CI 0·79–1·19), death or severe neurological sequelae or bilateral severe deafness (42·3% vs 44·3%; 0·92, 0·76–1·11), death or any neurological sequelae or any hearing loss (54·2% vs 57·4%; 0·89, 0·74–1·07), or death or severe bilateral hearing loss (36·4% vs 38·9%; 0·89, 0·73–1·69). However, dexamethasone seemed to reduce hearing loss among survivors (24·1% vs 29·5%; 0·77, 0·60–0·99, p=0·04). Dexamethasone had no effect in any of the prespecified subgroups, including specific causative organisms, pre-dexamethasone antibiotic treatment, HIV status, or age. Pooling of the mortality data with those of all other published trials did not significantly change the results.InterpretationAdjunctive dexamethasone in the treatment of acute bacterial meningitis does not seem to significantly reduce death or neurological disability. There were no significant treatment effects in any of the prespecified subgroups. The benefit of adjunctive dexamethasone for all or any subgroup of patients with bacterial meningitis thus remains unproven.FundingWellcome Trust UK.

The value of serial plasma nuclear and mitochondrial DNA levels in adult community-acquired bacterial meningitis

Increased levels of plasma nuclear and mitochondrial DNA have been reported in critically ill patients. We tested the hypothesis that plasma nuclear and mitochondrial DNA are substantially increased in acute bacterial meningitis and decrease after antimicrobial therapy, and that plasma nuclear and mitochondrial DNA levels can predict treatment outcomes. We examined serial plasma nuclear and mitochondrial DNA levels in 22 adult community-acquired bacterial meningitis (ACABM) patients. The plasma nuclear and mitochondrial DNA levels were also evaluated in 11 aseptic meningitis patients and 22 volunteer subjects during the study period. All of the both bacterial and aseptic meningitis groups had a higher plasma DNA levels on admission as compared with those of volunteer groups. Levels of plasma nuclear and mitochondrial DNA in ACABM cases were significantly increased initially and substantially decreased thereafter. Both plasma nuclear DNA and plasma mitochondrial DNA levels at presentation are significantly negative correlate with modified Barthel Index (average) (r = -0.639, P = 0.004 and r = -0.551, P = 0.018) at 3 months after discharge (average), respectively, in this study. Both higher plasma nuclear (cutoff value of >169 ng/ml) and mitochondrial DNA levels (cutoff value of >58.9 ng/ml) at presentation were associated with poor outcome in ACABM patients. Based on our results, the higher plasma DNA levels were associated with a poorer outcome. Therefore, we look forward to more prospective multicenter investigations specifically to confirm the predictive value of plasma DNA levels in outcome prediction.

Oxidative stress and myeloperoxidase activity during bacterial meningitis: Effects of febrile episodes and the BBB permeability

Objective To investigate participation of extracellular myeloperoxidase (MPO) in oxidative stress during different courses of the bacterial meningitis (BM). Materials and methods We sequentially assessed WBC count, blood-brain barrier (BBB) permeability, serum and cerebrospinal fluid (CSF) lipid peroxidation (LPO), MPO and antioxidative activity (AOA) in proven pediatric BM. Results BM patients exhibited increased systemic and local LPO and MPO, and reduced AOA, which was exaggerated in the febrile episodes. Serum MPO and LPO products were related to the BBB permeability at the baseline. CSF hydroperoxide level was influenced by the BBB permeability, CSF albumin concentration, and serum hydroperoxide ( r = 0.502; p < 0.001, and r = 0.611; p < 0.001, and r = 0.358; p < 0.001, respectively). CSF hydroperoxide and MPO correlated in complicated cases during the study. Conclusions These results suggest that CSF LPO and MPO were closely related in BM, had different courses if febrile episodes had occurred, but were partly influenced by the BBB permeability.

Adult community-acquired bacterial meningitis requiring ICU admission: epidemiological data, prognosis factors and adherence to IDSA guidelines

Numerous guidelines are available to guide empirical antimicrobial therapy (EAT) in acute bacterial meningitis (ABM) patients. We analysed prognosis factors and compliance to the Infectious Diseases Society of America (IDSA) guidelines in ABM patients requiring stay in an intensive care unit (ICU). A 10-year retrospective study, using prospectively collected data, in 82 ABM patients admitted to a 16-bed university-affiliated French ICU was undertaken. Seventeen patients (20.7%) died during ICU stay. Multivariate analysis isolated four factors associated with in-ICU death: alcoholism (P = 0.007), acute kidney injury (P = 0.006), age >60 years (P = 0.006) and ICU admission for neurological failure (P = 0.01). Causative pathogens were isolated for 62 (75.6%) patients, including 29 pneumococci, 14/28 of which were non-susceptible to penicillin. No characteristics, particularly recent hospitalisation and/or antibiotic delivery, was associated with penicillin susceptibility. Compliance to IDSA guidelines was 65%. Non-compliance concerned to be essentially the non-delivery or low dosage of vancomycin. Treatment compatible with IDSA guidelines was associated with a decreased ICU mortality in univariate (61.5% survival vs. 35.3%, P = 0.05) but not in multivariate analysis. In-ICU mortality associated with ABM remains high. Prognosis factors are related to the severity of disease or underlying conditions. Penicillin non-susceptible Streptococcus pneumoniae can occur without any of the usual predisposing factors.

Cerebrospinal Fluid Pleocytosis in Children in the Era of Bacterial Conjugate Vaccines

Although bacterial meningitis remains an important cause of childhood morbidity and mortality, the incidence of bacterial meningitis has greatly decreased with the advent of polysaccharide-protein conjugate vaccines in the past 2 decades. Most children with cerebrospinal fluid pleocytosis have aseptic rather than bacterial meningitis, raising the possibility that some patients may be managed as outpatients. In this article, we review the changing epidemiology of bacterial meningitis as well as the available clinical decision rules that may assist the clinician in distinguishing aseptic from bacterial meningitis in patients with cerebrospinal fluid pleocytosis.

Identifying Low-risk Patients for Bacterial Meningitis in Adult Patients with Acute Meningitis

To derive and validate a clinical prediction model with high sensitivity for differentiating aseptic meningitis (AM) patients from bacterial meningitis (BM) patients. We developed the model using the derivation cohort in a community rural hospital in Okinawa and assessed its performance using the validation cohort in a metropolitan urban hospital in Tokyo. There were 66 (39.5%) and 5 (17.9%) adult patients with BM among the derivation (n=167) and the validation cohort (n=28), respectively. Recursive partitioning analysis was used to determine the important classification variables and to develop a sensitive model to safely exclude BM. The model produced high- and low-risk groups based on the following: 1) Gram stain, 2) CSF neutrophil percent < or =15%, 3) CSF neutrophil count < or =150 cells/mm(3), and, 4) mental status change. Among the derivation cohort, there were 65 patients with BM in the high-risk group (n=76), while only one patient with BM was noted (sensitivity, 99%) in the low-risk group (n=91). Among the validation cohort, there were 5 patients with BM in the high-risk group (n=7), while no patient was classified with BM (sensitivity, 100%) in the low-risk group (n=21). This simple and sensitive model might be useful to safely identify low-risk patients for BM who would not require antibiotic treatment.

Chemical meningitis following cerebellopontine angle tumor surgery

Postoperative chemical meningitis mimics bacterial meningitis, complicating the diagnosis until results of cerebrospinal fluid (CSF) cultures can be obtained. We analyzed clinical and laboratory data from a series of 1146 patients to identify findings that could exclude bacterial meningitis. We reviewed the charts of patients who developed meningitis after cerebellopontine angle surgery. Lumbar puncture data from asymptomatic postoperative patients were our control. Clinical symptoms, CSF profiles, and serum white blood cell (WBC) counts were compared between patients with chemical meningitis, bacterial meningitis, and asymptomatic patients. The incidence of meningitis in our series of 1146 patients was 4.54 percent; 0.87 percent was culture-proven bacterial meningitis. The patients with bacterial meningitis had significantly higher CSF and serum WBC counts, and lower CSF glucose. The major difference between asymptomatic patients and those with chemical meningitis was the significantly lower ratio of CSF WBCs to red blood cells (RBCs) in asymptomatic patients. Patients with mild CSF leukocytosis and normal CSF glucose without high serum WBC counts or focal neurological deficits may be treated for chemical meningitis.

The value of serial cerebrospinal fluid 14-3-3 protein levels in adult community-acquired bacterial meningitis

Increased levels of cerebrospinal fluid (CSF) 14-3-3 proteins have been reported in acute bacterial meningitis. We tested the hypothesis that CSF 14-3-3 protein levels are substantially increased in acute bacterial meningitis and decreased after anti-microbial therapy, and that CSF 14-3-3 protein levels can predict treatment outcomes. We examined serial pan-CSF 14-3-3 (14-3-3-P) protein and five major isoform (beta, gamma, epsilon, eta, zeta) levels in 29 adult community-acquired bacterial meningitis (ACABM) patients. The CSF 14-3-3 protein levels were also evaluated in 12 aseptic meningitis patients during the study period. All of the meningitis patients had a positive result on admission. Levels of CSF 14-3-3 protein in ACABM cases were significantly increased initially, and substantially decreased thereafter. Most of those who survived (survivors = 25 and non-survivors = 4) had nearly cleared their 14-3-3 protein from the CSF before discharge. Conversely, patients who died never cleared their CSF 14-3-3 protein. The median value of CSF 14-3-3-P and 14-3-3 gamma, 14-3-3 eta and 14-3-3 epsilon isoforms on admission in the bacterial meningitis group were 173.7, 137.7, 42.2 and 9.1, respectively, which were statistically significant than those of the aseptic meningitis group (48.4, 39.6, 2.5 and 0, respectively). Stepwise logistic regression analysis showed only CSF 14-3-3 gamma isoform on admission was independently associated with outcome (P = 0.05, OR = 0.991). Serial 14-3-3 protein gamma isoform actually meets the major requirements for outcome prediction in the treatment of ACABM patients. Assay of the 14-3-3 protein gamma isoform should be added as a neuro-pathologic marker among the panel of conventional CSF parameters.

本邦における小児細菌性髄膜炎の動向 (2005～2006)

We surveyed pediatric bacterial meningitis epidemiology from January 2005 to December 2006 in Japan, with the following results. Bacterial meningitis cases numbered 246 -138 boys and 108 girls-, equivalent to 1.7-1.72 children of 1,000 hospitalized in pediatrics per year. The age distribution for infection was highest in those under 1 year of age and decreased with increasing age, Haemophilus influenzae was the most common infection causing the pathogen, followed by Streptococcus pneumoniae, group B streptococcus, and Escherichia coli. The relationship between causative pathogens and age distribution was as follows: group B streptococcus and E. coli were major pathogens in patients under 4 months old and H. influenzae and S. pneumoniae in those over 4 months old. Susceptibility tests at individual facilities showed 59.3% of H. influen- zae isolates and 69.3% of S. pneumoniae isolates in 2004 to be drug-resistant. Ampicillin and cephem antibiotics are effective against GBS, E. coli, and Listeria, so combined of ampicillin and cephem antibiotics are used as first-line antibiotics in many facilities in patients under 4 month old and combined of carbapenem antibiotics effective against PRSP and cephem effective against H. influenzae were the first choice against childhood bacterial meningitis in patients over 4 month old.

Bacterial meningitis in children experienced at a university hospital, 1993-2006

Purpose : Despite the seriousness of bacterial meningitis in children, there is little information on the incidence, causative organisms, mortality rate and age distribution. We studied the frequency by age group and causal pathogens, and clinical characteristics in children with bacterial meningitis in the private sector in Korea. Methods : The medical records containing the data on bacterial meningitis patients under 18 years of age confirmed by cerebrospinal fluid (CSF) findings were retrospectively analyzed from September, 1993 to August, 2006 at Ewha Womans University Mokdong Hospital. Results : Eighty-one cases of bacterial meningitis were observed. Overall the most common organism was Streptococcus agalactiae (group B streptococcus, GBS) (30 cases, 37.0%) followed by Haemophilus influenzae (22 cases, 27.2%), Streptococcus pneumoniae (12 cases, 14.8%), Escherichia coli (3 cases, 3.7%), Neisseria meningitidis (1 case, 1.2%) and others (13 cases, 16.0%). In neonates and young infants under 2 months, the most common organism was GBS. In children between 3 months, and 5 years, the most common organism was H. influenzae. S. pneumoniae was the most common organism in children over 5 years of age. Thirty-one patients (38.3%) had complications. Of all ages, the mortality rate of bacterial meningitis markedly decreased compared with the previously reported rate. Conclusion : In neonates, GBS meningitis was most common. The frequency of H. influenzae meningitis decreased after the introduction of H. influenzae type b vaccination. A strategy for the prevention of GBS meningitis in neonates should be established. The influence of the pneumococcal conjugate vaccine on S. pneumoniae meningitis should be studied.

Differential diagnosis between viral and bacterial meningitis in children

The differential diagnosis between viral meningitis and bacterial meningitis is often very difficult. The results of peripheral blood and spinal fluid analysis are not 100% accurate. We tried to find a useful 'bedside' decision-making tool, based on laboratory results readily available at the emergency department. Retrospective study design. Analysis of a consecutive series of all children (age 0-15 years) admitted to the paediatric ward because of a viral or bacterial meningitis, in the period from 1997 to September 2005. Seventy-one children with viral and 21 with bacterial meningitis were included. Bacterial meningitis occurred at much younger ages than viral meningitis. The paediatrician decided to administer antibiotics in 41 of 71 children with viral meningitis and in all children with bacterial meningitis. We developed a 'bacterial meningitis score' based on C-reactive protein in peripheral blood, as well as glucose and protein in cerebrospinal fluid. Using this score, we could distinguish 54 of 71 patients with viral meningitis from the group with bacterial meningitis. When the dispensing of antibiotics was based on this score, only 16 patients with viral meningitis would receive antibiotics. We present a bedside bacterial meningitis score. Using this bacterial meningitis score as a decision-making tool, we would be able to avoid antibiotics in a large number of children with viral meningitis. As this gives a 100% success rate, thus guaranteeing that bacterial meningitis patients would receive the proper therapy, our bacterial meningitis score could be an accurate decision-support tool.

Monocyte-derived dendritic cells in multiple sclerosis: The effect of bacterial infection

We investigated whether monocyte-derived dendritic cells (MDDCs) generated in vitro from bacteria-infected MS patients modified autoreactive T cells activation patterns. T cell clones (TCCs) stimulated with MDDCs from infected MS patients responded with maximal proliferation, inducing IL-12, IL-17 and IFN-γ secretion, at concentrations significantly lower than after incubation with MDDCs isolated from uninfected individuals and bacterial meningitis (BM) patients. Moreover, infected MDDCs promoted TCCs survival, and secreted more IL-12, IL-18, and IL-23. Finally, MDDCs from infected MS subjects showed higher expression of myeloid differentiation factor 88 (MyD88), as well as of HLA-DR, CD1a, CD80, CD86, CD273, CD40, CD83 and CCR7 when compared to MDDCs from uninfected MS individuals, and BM patients. Thus, activation of the innate immune system by microbial products in MS patients affects the generation MDDCs and their ability to modify autoreactive T cell activation patterns, which may be linked to MS relapse induction during bacterial infections.