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Find video protocols related to scientific articles indexed in Pubmed.
Epidemiology of invasive meningococcal disease in the Netherlands, 1960-2012: an analysis of national surveillance data.
Lancet Infect Dis
PUBLISHED: 08-04-2014
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Epidemiological data for invasive meningococcal disease is essential for public health policy and vaccine development. We analysed national surveillance data from the Netherlands for PorA coverage of two PorA-based meningococcal serogroup B vaccines to describe the epidemiology of invasive meningococcal disease.
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A decade of herd protection after introduction of meningococcal serogroup C conjugate vaccination.
Clin. Infect. Dis.
PUBLISHED: 07-28-2014
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Vaccination with meningococcal serogroup C (MenC) conjugate (MCC) polysaccharide vaccines led to a substantial decline in MenC disease in the vaccinated and the unvaccinated population. The decline in the unvaccinated population can be explained by herd protection by reduced colonization of meningococci expressing the MenC capsule. The duration of such herd protection is unknown.
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Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.
Trials
PUBLISHED: 06-25-2014
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Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes.
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Outcome in patients with bacterial meningitis presenting with a minimal Glasgow Coma Scale score.
Neurol Neuroimmunol Neuroinflamm
PUBLISHED: 06-01-2014
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In bacterial meningitis, a decreased level of consciousness is predictive for unfavorable outcome, but the clinical features and outcome in patients presenting with a minimal score on the Glasgow Coma Scale are unknown.
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Genetic risk load according to the site of intracranial aneurysms.
Neurology
PUBLISHED: 05-30-2014
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We investigated whether risk alleles of single nucleotide polymorphisms associated with intracranial aneurysm (IA) are enriched in patients with familial IA, IA located at the middle cerebral artery (MCA), or IA rupture at a younger age.
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Meningitis caused by a lipopolysaccharide deficient Neisseria meningitidis.
J. Infect.
PUBLISHED: 05-21-2014
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Lipopolysaccharide (LPS) is a major component of the Neisseria meningitidis outer membrane. Here we report a patient with meningococcal meningitis of which the causative isolate lacked LPS. Thus far, no naturally occurring LPS-deficient meningococcal isolate has been known to cause clinical disease.
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Bacterial meningitis.
Handb Clin Neurol
PUBLISHED: 04-20-2014
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Bacterial meningitis is a neurologic emergency. Vaccination against common pathogens has decreased the burden of disease. Early diagnosis and rapid initiation of empiric antimicrobial and adjunctive therapy are vital. Therapy should be initiated as soon as blood cultures have been obtained, preceding any imaging studies. Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, and an altered level of consciousness but signs may be scarce in children, in the elderly, and in meningococcal disease. Host genetic factors are major determinants of susceptibility to meningococcal and pneumococcal disease. Dexamethasone therapy has been implemented as adjunctive treatment of adults with pneumococcal meningitis. Adequate and prompt treatment of bacterial meningitis is critical to outcome. In this chapter we review the epidemiology, pathophysiology, and management of bacterial meningitis.
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Update on the Preventive Antibiotics in Stroke Study (PASS): a randomised controlled phase 3 clinical trial.
Trials
PUBLISHED: 02-24-2014
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Stroke is a leading cause of death worldwide. Infections after stroke occur in 30% of stroke patients and are strongly associated with unfavourable outcome. Preventive antibiotic therapy lowers infection rate in patients after stroke, however, the effect of preventive antibiotic treatment on functional outcome after stroke has not yet been investigated.The Preventive Antibiotics in Stroke Study (PASS) is an ongoing, multicentre, prospective, randomised, open-label, blinded end point trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 hours intravenously for four-days, in addition to stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. Aim of the study is to assess whether preventive antibiotic treatment improves functional outcome at three months by preventing infections.
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Clinical characteristics and outcome of brain abscess: systematic review and meta-analysis.
Neurology
PUBLISHED: 01-29-2014
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To define clinical characteristics, causative organisms, and outcome, and evaluate trends in epidemiology and outcome of brain abscesses over the past 60 years.
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Cerebrospinal fluid complement activation in patients with pneumococcal and meningococcal meningitis.
J. Infect.
PUBLISHED: 01-09-2014
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Recent research into the treatment of bacterial meningitis has examined the innate immune system, specifically the complement system, as a potential target for adjuvant therapy. However, the effects of blocking the complement system may be pathogen dependent.
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Meningococcal serogroup Y lpxL1 variants from South Africa are associated with clonal complex 23 among young adults.
J. Infect.
PUBLISHED: 01-04-2014
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To determine the genotypes of serogroup Y meningococcus (MenY), and to determine the prevalence of and identify factors associated with MenY lpxL1 variants.
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Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis.
PLoS ONE
PUBLISHED: 01-01-2014
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We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment.
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Streptococcus pneumoniae arginine synthesis genes promote growth and virulence in pneumococcal meningitis.
J. Infect. Dis.
PUBLISHED: 12-13-2013
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Streptococcus pneumoniae (pneumococcus) is a major human pathogen causing pneumonia, sepsis and bacterial meningitis. Using a clinical phenotype based approach with bacterial whole-genome sequencing we identified pneumococcal arginine biosynthesis genes to be associated with outcome in patients with pneumococcal meningitis. Pneumococci harboring these genes show increased growth in human blood and cerebrospinal fluid (CSF). Mouse models of meningitis and pneumonia showed that pneumococcal strains without arginine biosynthesis genes were attenuated in growth or cleared, from lung, blood and CSF. Thus, S. pneumoniae arginine synthesis genes promote growth and virulence in invasive pneumococcal disease.
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Traumatic brain injury in rats induces lung injury and systemic immune suppression.
J. Neurotrauma
PUBLISHED: 10-24-2013
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Abstract Traumatic brain injury (TBI) is frequently complicated by acute lung injury, which is predictive for poor outcome. However, it is unclear whether lung injury develops independently or as a result of mechanical ventilation after TBI. Further, TBI is strongly associated with the development of pneumonia, suggesting a specific vulnerability for the development of nosocomial infections in the lung after TBI. In this study, we evaluated whether indeed pulmonary injury and immune suppression develop spontaneously in an animal model of mild TBI (mTBI). TBI was induced in male PVG rats by closed-head trauma using a weight-drop device. Subsequently, we evaluated the effects of this on the lungs as well as on the excitability of the systemic immune system. Finally, we performed an experiment in which TBI was followed by induction of pneumonitis and evaluated whether TBI affects the severity of subsequent pneumonitis induced by intratracheal instillation of heat-killed Staphylococcus aureus. mTBI resulted in significant lung injury, as evidenced by pulmonary edema, protein leakage to the alveolar compartment, and increased concentrations of interleukin-1 and -6 in broncho alveolar lavage fluid (all p<0.05?vs. sham-treated animals). Further, after TBI, the release of tumor necrosis factor alpha was decreased when whole blood was stimulated ex vivo (p<0.05 TBI vs. sham), indicating systemic immune suppression. When TBI was followed by pneumonitis, the severity of subsequent pneumonitis was not different in rats previously subjected to TBI or sham treatment (p>0.05), suggesting that systemic immune suppression is not translated toward the pulmonary compartment in this specific model. We here show that during mild experimental TBI, acute pulmonary injury, as well as a decrease in the excitability of the systemic immune system, can be observed.
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Inflammasome activation mediates inflammation and outcome in humans and mice with pneumococcal meningitis.
BMC Infect. Dis.
PUBLISHED: 07-25-2013
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Inflammasomes are multi-protein intracellular signaling complexes that have recently been hypothesized to play a role in the regulation of the inflammation response. We studied associations between inflammasome-associated cytokines IL-1? and IL-18 in cerebrospinal fluid (CSF) of patients with bacterial meningitis and clinical outcome, and pneumococcal serotype. In a murine model of pneumococcal meningitis we examined the pathophysiological roles of two inflammasome proteins, NLRP3 (Nod-like receptor protein-3) and adaptor protein ASC (apoptosis-associated speck-like protein).
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Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients.
J Neuroinflammation
PUBLISHED: 07-19-2013
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Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery.
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Plasminogen activator inhibitor-1 influences cerebrovascular complications and death in pneumococcal meningitis.
Acta Neuropathol.
PUBLISHED: 06-28-2013
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Cerebrovascular complications are common in pneumococcal meningitis and are a main determinant of unfavourable outcome and death. We hypothesized that plasminogen activator inhibitor-1 (PAI-1) is a major contributor to cerebrovascular complications and death in pneumococcal meningitis. In a nationwide prospective cohort study we evaluated the effect of the 4G/5G polymorphism (rs1799889) in SERPINE1 (coding for PAI-1) on cerebrovascular complications and outcome in adults with pneumococcal meningitis proven by cerebrospinal fluid (CSF) culture. From 2006 to 2011, a total of 991 adult patients with community-acquired bacterial meningitis were included in the cohort and 712 had pneumococcal meningitis. The rs1799889 5G/5G genotype was associated with an increased risk of unfavourable outcome [odds ratio (OR) 1.69, 95 % confidence interval (CI) 1.03-2.78] and mortality (OR 2.20, 95 % CI 1.02-4.86) in white adults with pneumococcal meningitis. rs1799889 was associated with CSF PAI-1 concentrations (P = 0.048), and white patients homozygous for the low PAI-1 producing genotype (5G/5G) had a significantly higher risk for cerebral infarctions (P = 0.015) and haemorrhages (P = 0.005). Subsequently, we assessed the functionality of PAI-1 in a pneumococcal meningitis mouse model, using Serpine1 knockout mice. Consistent with the human data, Serpine1-deficient mice had increased mortality and cerebral haemorrhages compared to wild-type mice. We conclude PAI-1 is protective for death in humans and mice with pneumococcal meningitis by reducing cerebrovascular complications.
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Corticosteroids for acute bacterial meningitis.
Cochrane Database Syst Rev
PUBLISHED: 06-05-2013
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In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.
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Endocarditis in adults with bacterial meningitis.
Circulation
PUBLISHED: 04-17-2013
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Endocarditis may precede or complicate bacterial meningitis, but the incidence and impact of endocarditis in bacterial meningitis are unknown.
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Listeria monocytogenes sequence type 6 and increased rate of unfavorable outcome in meningitis: epidemiologic cohort study.
Clin. Infect. Dis.
PUBLISHED: 04-16-2013
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We analyzed clinical characteristics, treatment, genetic diversity, and outcome of 92 adults with Listeria monocytogenes meningitis included in 2 prospective nationwide cohort studies.
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Risk score for identifying adults with CSF pleocytosis and negative CSF Gram stain at low risk for an urgent treatable cause.
J. Infect.
PUBLISHED: 04-01-2013
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We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause.
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Update on bacterial meningitis: epidemiology, trials and genetic association studies.
Curr. Opin. Neurol.
PUBLISHED: 03-16-2013
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Bacterial meningitis is a life-threatening disease that continues to inflict a heavy toll. We reviewed recent advances in vaccination, randomized studies on treatment, and genetic association studies in bacterial meningitis.
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Stroke: long-term effect of infections after stroke.
Nat Rev Neurol
PUBLISHED: 02-19-2013
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A recent study has shown that infection in the first 2 weeks after stroke correlates with 3-year mortality, and that risk of infection is highest in patients with dysphagia, urinary catheterization, or intracerebral haemorrhage. Studies are needed to assess treatment strategies to prevent early infection in patients with acute stroke.
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Bacterial meningitis in adults after splenectomy and hyposplenic states.
Mayo Clin. Proc.
PUBLISHED: 02-01-2013
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To examine the occurrence, disease course, prognosis, and vaccination status of patients with community-acquired bacterial meningitis with a history of splenectomy or functional hyposplenia.
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Signalling or binding: the role of the platelet-activating factor receptor in invasive pneumococcal disease.
Cell. Microbiol.
PUBLISHED: 01-07-2013
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Streptococcus pneumoniae (the pneumococcus) is an opportunistic human pathogen, which causes serious invasive disease such as pneumonia, bacteraemia and meningitis. The interaction of the bacteria with host receptors precedes the development of invasive disease. One host receptor implicated in pneumococcal adhesion to, invasion of and ultimately translocation of cell layers is the platelet-activating factor receptor (PAFR). PAFR is a G-protein coupled receptor which binds PAF, a potent phospholipid activator involved in many leucocyte functions, platelet aggregation and inflammation. PAFR has been proposed to bind S.?pneumoniae and as such facilitate adhesion to, uptake by and transcytosis of endothelial cells leading to invasive disease. However, there is a shortage of biochemical data supporting direct interaction between PAFR and the bacteria, in addition to conflicting data on its role in development of invasive pneumococcal disease (IPD). In this review, we will discuss current literature on PAFR and S.?pneumoniae and other pathogens,including data concerning human PAFR genetic variation related to IPD clinical aspects, to shed light on the importance of PAFR in IPD. Clarification of the role of this receptor in IPD development has the potential to enable the development of novel therapeutic strategies for treating pneumococcal disease by interfering with the PAFR.
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Genetic variation and cerebrospinal fluid levels of mannose binding lectin in pneumococcal meningitis patients.
PLoS ONE
PUBLISHED: 01-01-2013
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It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05-64.1; p?=?0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39-3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis.
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An analysis of the sequence variability of meningococcal fHbp, NadA and NHBA over a 50-year period in the Netherlands.
PLoS ONE
PUBLISHED: 01-01-2013
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Studies of meningococcal evolution and genetic population structure, including the long-term stability of non-random associations between variants of surface proteins, are essential for vaccine development. We analyzed the sequence variability of factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisseria adhesin A (NadA), three major antigens in the multicomponent meningococcal serogroup B vaccine 4CMenB. A panel of invasive isolates collected in the Netherlands over a period of 50 years was used. To our knowledge, this strain collection covers the longest time period of any collection available worldwide. Long-term persistence of several antigen sub/variants and of non-overlapping antigen sub/variant combinations was observed. Our data suggest that certain antigen sub/variants including those used in 4CMenB are conserved over time and promoted by selection.
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Progressive multifocal leukoencephalopathy in transplant recipients.
Ann. Neurol.
PUBLISHED: 08-09-2011
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Transplant recipients are at risk of developing progressive multifocal leukoencephalopathy (PML), a rare demyelinating disorder caused by oligodendrocyte destruction by JC virus.
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Pathogenesis and pathophysiology of pneumococcal meningitis.
Clin. Microbiol. Rev.
PUBLISHED: 07-08-2011
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Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.
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Post-stroke infection: a systematic review and meta-analysis.
BMC Neurol
PUBLISHED: 05-19-2011
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stroke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome.
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Association of chronic meningococcemia with infection by meningococci with underacylated lipopolysaccharide.
J. Infect.
PUBLISHED: 02-10-2011
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Chronic meningococcemia is an uncommon manifestation of meningococcal disease. Our objective was to asses whether a bacterial factor, a mutation in the lpxL1 gene resulting in underacylated lipopolysaccharide, might be important in chronic meningococcemia.
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Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis.
J. Clin. Invest.
PUBLISHED: 02-09-2011
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Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor-deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.
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Preventive antibiotics in stroke study: rationale and protocol for a randomised trial.
Int J Stroke
PUBLISHED: 12-16-2010
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Stroke is a leading cause of death worldwide. Fever after stroke is a strong predictor of a poor outcome. Infections occur in up to 40% of patients with stroke and have also been associated with poor outcomes. Preventive antibiotic therapy lowers the infection rates in patients after stroke, as shown in a recent meta-analysis of randomised studies. Phase III trials evaluating the effect of antibiotic prophylaxis on clinical outcomes in sufficient numbers of patients with stroke have, however, not been performed to date. Ceftriaxone, an off-patent medicine, is an antibiotic with a broad defence against the bacteria that cause the most common infections after stroke. Preventive antibiotic therapy with ceftriaxone may potentially reduce poor outcome after acute stroke and, therefore, a randomised clinical trial is warranted.
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Corticosteroids for acute bacterial meningitis.
Cochrane Database Syst Rev
PUBLISHED: 09-09-2010
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In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.
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Hydrocephalus in adults with community-acquired bacterial meningitis.
Neurology
PUBLISHED: 09-08-2010
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To evaluate the occurrence, treatment, and outcome of hydrocephalus complicating community-acquired bacterial meningitis in adults.
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Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis.
Clin. Microbiol. Rev.
PUBLISHED: 07-09-2010
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The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the important etiological agents and populations at risk to ascertain public health measures and ensure appropriate management. In this review, we describe the changing epidemiology of bacterial meningitis in the United States and throughout the world by reviewing the global changes in etiological agents followed by specific microorganism data on the impact of the development and widespread use of conjugate vaccines. We provide recommendations for empirical antimicrobial and adjunctive treatments for clinical subgroups and review available laboratory methods in making the etiological diagnosis of bacterial meningitis. Finally, we summarize risk factors, clinical features, and microbiological diagnostics for the specific bacteria causing this disease.
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Diffuse cerebral intravascular coagulation and cerebral infarction in pneumococcal meningitis.
Neurocrit Care
PUBLISHED: 06-08-2010
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There is a widely held belief that cerebral infarction after bacterial meningitis is always caused by vasculitis; however, evidence is weak. We hypothesized that diffuse cerebral intravascular coagulation is an additional explanation of cerebral infarction in patients with pneumococcal meningitis.
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Cognitive functioning and quality of life nine years after bacterial meningitis.
J. Infect.
PUBLISHED: 05-21-2010
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To examine recovery of psychological functioning nine years after meningitis.
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Host genetics and outcome in meningococcal disease: a systematic review and meta-analysis.
Lancet Infect Dis
PUBLISHED: 03-26-2010
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Various genes regulate the intensity of the inflammatory and coagulation response to infection and therefore might determine the severity and outcome of meningococcal disease. We systematically reviewed the published work for case-control studies on the influence of host genetics on severity and outcome in meningococcal disease and identified 27 studies including 7245 patients, with an overall mortality of 10% (range 1-19%). Despite flaws in the methods of the studies there was a clear association of host genetics with mortality and severity in meningococcal disease. Polymorphisms in SERPINE1 (odds ratio [OR] 2.23, 95% CI 1.48-3.35), IL1RN (OR 1.85, 95% CI 1.25-2.76) and IL1B (OR 1.81, 95% CI 1.09-2.97) were associated with mortality in our meta-analyses. In conclusion, gene variation influences severity and mortality in meningococcal disease. Polymorphisms might have potential as prognostic markers or to determine tailor-made adjunctive therapy. Carefully designed, prospective, whole-genome association studies and randomised clinical trials of treatments in specific genetic subgroups are needed.
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Systemic infection and delirium: when cytokines and acetylcholine collide.
Lancet
PUBLISHED: 03-02-2010
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Systemic infection and drugs with anticholinergic effects are well-recognised and prevalent risk factors for delirium in elderly people. Experimental findings and neuropathological observations suggest that activation of microglia is pivotal for mediation of the behavioural effects of systemic infections. The microglial response is usually regulated tightly, but defensive features could turn neurotoxic once microglial cells escape from cholinergic inhibition. A self-propelling neuroinflammatory reaction might follow, and this cascade could account for the strong association between delirium and long-term cognitive impairment and even dementia. Here, we propose a hypothetical model, suggesting that poor outcome after delirium can be averted in vulnerable elderly people by use of readily available drugs. Agents that either restore cholinergic control of microglia or directly inhibit neuroinflammation warrant testing in clinical trials.
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Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data.
Lancet Neurol
PUBLISHED: 02-03-2010
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Dexamethasone 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.
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Bacterial meningitis.
Handb Clin Neurol
PUBLISHED: 01-19-2010
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Bacterial meningitis is a neurological emergency. Empiric antimicrobial and adjunctive therapy should be initiated as soon as a single set of blood cultures has been obtained. Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, vomiting, photophobia, and an altered level of consciousness. The peripheral white blood cell count with a left shift, an elevated serum procalcitonin and C-reactive protein, and a cerebrospinal fluid pleocytosis with a predominance of polymorphonuclear leukocytes, and a decreased glucose concentration are predictive of bacterial meningitis. Patients with documented bacterial meningitis and those in whom the diagnosis is a strong possibility should be admitted to the intensive care unit. Timely recognition of bacterial meningitis and initiation of therapy are critical to outcome.
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Community-acquired bacterial meningitis in alcoholic patients.
PLoS ONE
PUBLISHED: 01-18-2010
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Alcoholism is associated with susceptibility to infectious disease, particularly bacterial pneumonia. In the present study we described characteristics in alcoholic patients with bacterial meningitis and delineate the differences with findings in non-alcoholic adults with bacterial meningitis.
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Incidence of and risk factors for skin cancer after heart transplant.
Arch Dermatol
PUBLISHED: 12-23-2009
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To examine the incidence, tumor burden, and risk factors for nonmelanoma and other skin cancer types in this heart transplant cohort.
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The effect of HIV infection on adult meningitis in Indonesia: a prospective cohort study.
AIDS
PUBLISHED: 09-23-2009
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Indonesia has a concentrated but rapidly growing HIV epidemic. We examined the effect of HIV on causative organisms, clinical features and prognosis of adult meningitis.
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Preventive antibiotics for infections in acute stroke: a systematic review and meta-analysis.
Arch. Neurol.
PUBLISHED: 09-16-2009
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To provide a systematic overview and meta-analysis of randomized clinical trials evaluating preventive antibiotics in patients with acute stroke.
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Macrophage migration inhibitory factor, infection, the brain, and corticosteroids.
Crit Care
PUBLISHED: 07-27-2009
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Bacterial meningitis is a complex disorder in which injury is caused, in part, by the causative organism and, in part, by the hosts own inflammatory response. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and a neuro-endocrine mediator that might play a role in pneumococcal meningitis. Here, we discuss the role of MIF in infection, the brain, and corticosteroids and conclude that experimental meningitis studies have to determine whether MIF is a potential target for adjunctive therapy in pneumococcal meningitis.
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Incidence and clinical characteristics of ocular infections after heart transplantation: a retrospective cohort study.
Clin Transplant
PUBLISHED: 06-30-2009
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Ocular infections associated with organ transplantation are well documented following renal and liver transplantation; however, few studies have reported ocular infections following heart transplant.
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Delayed life-threatening subdural hematoma after minor head injury in a patient with severe coagulopathy: a case report.
Cases J
PUBLISHED: 05-05-2009
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Minor head injury is a frequent cause for neurologic consultation and imaging. Most patients with minor head injury will make an uneventful recovery, but in a very small proportion of these patients life threatening intracranial complications occur. We describe a patient on oral anticoagulation therapy, and severely impaired coagulation, with normal head computed tomography on admission, who developed a subdural hematoma requiring surgery 12 hours later. Current guidelines and literature for the management of minor head injury are discussed.
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No major neurologic complications with sirolimus use in heart transplant recipients.
Mayo Clin. Proc.
PUBLISHED: 04-03-2009
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To determine whether sirolimus therapy is associated with neurologic complications, including stroke, among heart transplant recipients.
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Hyperglycemia in bacterial meningitis: a prospective cohort study.
BMC Infect. Dis.
PUBLISHED: 03-25-2009
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Hyperglycemia has been associated with unfavorable outcome in several disorders, but few data are available in bacterial meningitis. We assessed the incidence and significance of hyperglycemia in adults with bacterial meningitis.
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Naturally occurring lipid A mutants in neisseria meningitidis from patients with invasive meningococcal disease are associated with reduced coagulopathy.
PLoS Pathog.
PUBLISHED: 03-25-2009
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Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial outer membrane, is sensed by mammalian cells through Toll-like receptor 4 (TLR4), resulting in activation of proinflammatory cytokine pathways. TLR4 recognizes the lipid A moiety of the LPS molecule, and the chemical composition of the lipid A determines how well it is recognized by TLR4. N. meningitidis has been reported to produce lipid A with six acyl chains, the optimal number for TLR4 recognition. Indeed, meningococcal sepsis is generally seen as the prototypical endotoxin-mediated disease. In the present study, we screened meningococcal disease isolates from 464 patients for their ability to induce cytokine production in vitro. We found that around 9% of them were dramatically less potent than wild-type strains. Analysis of the lipid A of several of the low-activity strains by mass spectrometry revealed they were penta-acylated, suggesting a mutation in the lpxL1 or lpxL2 genes required for addition of secondary acyl chains. Sequencing of these genes showed that all the low activity strains had mutations that inactivated the lpxL1 gene. In order to see whether lpxL1 mutants might give a different clinical picture, we investigated the clinical correlate of these mutations in a prospective nationwide observational cohort study of adults with meningococcal meningitis. Patients infected with an lpxL1 mutant presented significantly less frequently with rash and had higher thrombocyte counts, consistent with reduced cytokine induction and less activation of tissue-factor mediated coagulopathy. In conclusion, here we report for the first time that a surprisingly large fraction of meningococcal clinical isolates have LPS with underacylated lipid A due to mutations in the lpxL1 gene. The resulting low-activity LPS may have an important role in virulence by aiding the bacteria to evade the innate immune system. Our results provide the first example of a specific mutation in N. meningitidis that can be correlated with the clinical course of meningococcal disease.
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Neuromuscular diseases after cardiac transplantation.
J. Heart Lung Transplant.
PUBLISHED: 03-17-2009
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Cardiac transplantation is a therapeutic option in end-stage heart failure. Peripheral nervous system (PNS) disease is known to occur in cardiac transplant recipients but has not been fully characterized.
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Host genetic susceptibility to pneumococcal and meningococcal disease: a systematic review and meta-analysis.
Lancet Infect Dis
PUBLISHED: 02-12-2009
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Streptococcus pneumoniae and Neisseria meningitidis can cause sepsis and meningitis. Several risk factors for pneumococcal and meningococcal disease have been identified, but the cause of basic differences in susceptibility between individuals and populations is unknown. Single-nucleotide polymorphisms are thought to explain interindividual differences in susceptibility. New technologies provide the opportunity to study the genetic basis of susceptibility to these diseases. In recent years, several studies have been published on these polymorphisms in pneumococcal and meningococcal disease, many with apparently conflicting results. Herein we provide a systematic overview of all polymorphisms studied for a relation with susceptibility to pneumococcal and meningococcal disease. We also propose an initiative to pool genetic data on pneumococcal and meningococcal meningitis in one biobank.
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Resistance to trimethoprim/sulfamethoxazole and Tropheryma whipplei.
Int. J. Antimicrob. Agents
PUBLISHED: 01-30-2009
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Whipples disease (WD) is a chronic infection caused by Tropheryma whipplei. A 1-year treatment of oral trimethoprim/sulfamethoxazole (SXT) is commonly used. Advances in the culture of T. whipplei have allowed for full genome sequencing and antibiotic susceptibility testing, which has demonstrated resistance of T. whipplei to trimethoprim. Several mutations in the folP gene that encodes dihydropteroate synthase, the target of sulphonamides, has been reported for one patient with clinically acquired resistance to SXT. Here we report three new patients who experienced clinically acquired resistance to SXT during treatment and one patient with biological failure. Sixty-two folP sequences from DNA samples of 59 WD patients were also obtained. Among the detected amino acid changes, two positions (N4S and S234F) significantly predicted secondary sulfamethoxazole failure (four of five). We suggest that these mutations should be detected at the time of WD diagnosis by sequencing folP in order to avoid sulfamethoxazole monotherapy.
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Community acquired Staphylococcus aureus meningitis in adults.
Scand. J. Infect. Dis.
PUBLISHED: 01-30-2009
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We present 9 patients with community acquired Staphylococcus aureus meningitis. Foci of infection outside the central nervous system were present in 8 (89%) patients, mostly endocarditis and pneumonia. Cardiorespiratory complications occurred frequently and 6 patients died (67%). Identification and treatment of the primary focus of infection should be a priority in these patients.
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Daptomycin in experimental murine pneumococcal meningitis.
BMC Infect. Dis.
PUBLISHED: 01-16-2009
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Daptomycin, a lipopeptide antibiotic, could be an alternative to vancomycin for treatment of pneumococcal meningitis. We determined the activity of daptomycin versus vancomycin, with dexamethasone as an adjuvant, in a murine model of pneumococcal meningitis.
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Delayed cerebral thrombosis in bacterial meningitis: a prospective cohort study.
Intensive Care Med
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To study the incidence and clinical characteristics of delayed cerebral thrombosis in bacterial meningitis patients.
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Prevalence and clinical course in invasive infections with meningococcal endotoxin variants.
PLoS ONE
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Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.
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Dexamethasone and long-term survival in bacterial meningitis.
Neurology
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Data on the long-term effect of dexamethasone on survival in bacterial meningitis are lacking.
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Effect of vaccines on bacterial meningitis worldwide.
Lancet
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Three bacteria--Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis--account for most acute bacterial meningitis. Measurement of the effect of protein-polysaccharide conjugate vaccines is most reliable for H influenzae meningitis because one serotype and one age group account for more than 90% of cases and the incidence has been best measured in high-income countries where these vaccines have been used longest. Pneumococcal and meningococcal meningitis are caused by diverse serotypes and have a wide age distribution; measurement of their incidence is complicated by epidemics and scarcity of surveillance, especially in low-income countries. Near elimination of H influenzae meningitis has been documented after vaccine introduction. Despite greater than 90% reductions in disease attributable to vaccine serotypes, all-age pneumococcal meningitis has decreased by around 25%, with little data from low-income settings. Near elimination of serogroup C meningococcal meningitis has been documented in several high-income countries, boding well for the effect of a new serogroup A meningococcal conjugate vaccine in the African meningitis belt.
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Advances in treatment of bacterial meningitis.
Lancet
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Bacterial meningitis kills or maims about a fifth of people with the disease. Early antibiotic treatment improves outcomes, but the effectiveness of widely available antibiotics is threatened by global emergence of multidrug-resistant bacteria. New antibiotics, such as fluoroquinolones, could have a role in these circumstances, but clinical data to support this notion are scarce. Additionally, whether or not adjunctive anti-inflammatory therapies (eg, dexamethasone) improve outcomes in patients with bacterial meningitis remains controversial; in resource-poor regions, where the disease burden is highest, dexamethasone is ineffective. Other adjunctive therapeutic strategies, such as glycerol, paracetamol, and induction of hypothermia, are being tested further. Therefore, bacterial meningitis is a substantial and evolving therapeutic challenge. We review this challenge, with a focus on strategies to optimise antibiotic efficacy in view of increasingly drug-resistant bacteria, and discuss the role of current and future adjunctive therapies.
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Dilemmas in the diagnosis of acute community-acquired bacterial meningitis.
Lancet
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Rapid diagnosis and treatment of acute community-acquired bacterial meningitis reduces mortality and neurological sequelae, but can be delayed by atypical presentation, assessment of lumbar puncture safety, and poor sensitivity of standard diagnostic microbiology. Thus, diagnostic dilemmas are common in patients with suspected acute community-acquired bacterial meningitis. History and physical examination alone are sometimes not sufficient to confirm or exclude the diagnosis. Lumbar puncture is an essential investigation, but can be delayed by brain imaging. Results of cerebrospinal fluid (CSF) examination should be interpreted carefully, because CSF abnormalities vary according to the cause, patients age and immune status, and previous treatment. Diagnostic prediction models that use a combination of clinical findings, with or without test results, can help to distinguish acute bacterial meningitis from other causes, but these models are not infallible. We review the dilemmas in the diagnosis of acute community-acquired bacterial meningitis, and focus on the roles of clinical assessment and CSF examination.
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Subdural empyema in bacterial meningitis.
Neurology
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To evaluate the occurrence, treatment, and outcome of subdural empyema complicating community-acquired bacterial meningitis in adults.
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Meningococcal factor H binding protein fHbpd184 polymorphism influences clinical course of meningococcal meningitis.
PLoS ONE
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Factor H Binding protein (fHbp) is an important meningococcal virulence factor, enabling the meningococcus to evade the complement system, and a main target for vaccination. Recently, the structure of fHBP complexed with factor H (fH) was published. Two fHbp glutamic acids, E(283) and E(304), form salt bridges with fH, influencing interaction between fHbp and fH. Fifteen amino acids were identified forming hydrogen bonds with fH. We sequenced fHbp of 254 meningococcal isolates from adults with meningococcal meningitis included in a prospective clinical cohort to study the effect of fHbp variants on meningococcal disease severity and outcome. All fHbp of subfamily A had E304 substituted with T304. Of the 15 amino acids in fHbp making hydrogen bonds to fH, 3 were conserved, 11 show a similar distribution between the two fHbp subfamilies as the polymorphism at position 304. The proportion of patients infected with meningococci with fHbp of subfamily A with unfavorable outcome was 2.5-fold lower than that of patients infected with meningococci with fHbp of subfamily B (2 of 40 (5%) vs. 27 of 213 (13%) (P?=?0.28). The charge of 2 of 15 amino acids (at position 184 and 306) forming hydrogen bonds was either basic or acidic. The affinity of fHbp(K184) and of fHbp(D184) for recombinant purified human fH was assessed by Surface Plasmon Resonance and showed average K(D) of 2.60×10(-8) and 1.74×10(-8), respectively (ns). Patients infected with meningococci with fHbp(D184) were more likely to develop septic shock during admission (11 of 42 [26%] vs. 19 of 211 [9%]; P?=?0.002) resulting in more frequent unfavorable outcome (9 of 42 [21%] vs. 20 of 211 [10%]; P?=?0.026). In conclusion, we dentified fHBP(D184) to be associated with septic shock in patients with meningococcal meningitis.
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Common polymorphisms in the complement system and susceptiblity to bacterial meningitis.
J. Infect.
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Risk factors for susceptibility to bacterial meningitis have been identified, but basic causes of inter-individual differences in susceptibility are largely unknown.
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Genetic variation in inflammasome genes is associated with outcome in bacterial meningitis.
Immunogenetics
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Bacterial meningitis is a severe and deadly disease, most commonly caused by Streptococcus pneumoniae. Disease outcome has been related to severity of the inflammatory response in the subarachnoid space. Inflammasomes are intracellular signaling complexes contributing to this inflammatory response. The role of genetic variation in inflammasome genes in bacterial meningitis is largely unknown. In a prospective nationwide cohort of patients with pneumococcal meningitis, we performed a genetic association study and found that single-nucleotide polymorphisms in the inflammasome genes CARD8 (rs2043211) and NLRP1 (rs11621270) are associated with poor disease outcome. Levels of the inflammasome associated cytokines interleukin (IL)-1? and IL-18 in cerebrospinal fluid also correlated with clinical outcome, but were not associated with the CARD8 and NLRP1 polymorphisms. Our results implicate an important role of genetic variation in inflammasome genes in the regulation of inflammatory response and clinical outcome in patients with bacterial meningitis.
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Intracerebral hemorrhages in adults with community associated bacterial meningitis in adults: should we reconsider anticoagulant therapy?
PLoS ONE
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To study the incidence, clinical presentation and outcome of intracranial hemorrhagic complications in adult patients with community associated bacterial meningitis.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.