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Abstract

BACKGROUND: 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. OBJECTIVES: To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis. SEARCH METHODS: We searched CENTRAL 2012, Issue 12, MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), Web of Science (2010 to January 2013), CINAHL (2010 to January 2013) and LILACS (2010 to January 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality. MAIN RESULTS: Twenty-five studies involving 4121 participants were included. Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) orNeisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events. AUTHORS' CONCLUSIONS: Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.

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... Earlier studies were more restrictive and critical regarding the use of DXM as adjunctive therapy in the treatment of IMD, and those were based on the lack of proof regarding clinical or laboratory effi cacy of DXM in meningococcal meningitis (6-10), or in prevention of neurological and systemic meningococcal meningitis complications (11). Th e later studies on DXM as adjunctive therapy in meningococcal infections are more favourable regarding its use, stating that DXM in meningococcal meningitis has shown consistency and degree of benefi ts (12)(13)(14), it is not associated with any harm, and the rates of early complications like arthritis are lower (15,16). Further more, studies on the impact of DXM on experimental meningococcal sepsis in mice showed a benefi cial eff ect of DXM in addition to an appropriate antibiotic therapy, which is most likely due to the reduction of infl ammatory response by an early induction of IL-10 cytokine (4). ...
... Our earlier study on the eff ect of DXM on the course of invasive meningococcal disease showed the limited eff ect of DXM during the days of administration in cases of sepsis with meningitis, by normalizing the values of CSF glucose and protein; showing the positive eff ect on the normalization of the brain barrier permeability (5). Th is follow up study is in correlation with our earlier study, as well as with the studies that stated positive eff ects from DXM use on the course of invasive meningococcal disease (5,(12)(13)(14)(15)(16). Most of the analysed variables in our study show more favourable outcome in patients treated with DXM, although statistical significance was not reached, except for hospitalization length and WBC (at the end of DXM treatment). ...
Article
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Purpose Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. Methods In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Results Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. Conclusion The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease.
... Prior to the wide spread use of adjunctive steroids in bacterial meningitis 32,33 cerebral vascular alterations were devastating but common complications mediated by cerebral vasculitis, septic emboli, intraarterial thrombosis or disseminated intravascular coagulation 31,[34][35][36] . This emphasizes the need for speci c antiin ammatory drugs in bacterial meningitis 37,38 beyond adjuvant corticosteroid treatment which has been proven bene cial on case fatality rates in adult patients with pneumococcal meningitis but only in highincome countries 33 . ...
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Objective In community-acquired bacterial meningitis(CABM) intracranial vascular alterations are devastating complications which are triggered by neuroinflammation and result in worse clinical outcome. The neutrophil-to-lymphocyte ratio(NLR) represents a reliable parameter of the inflammatory response. So far, in CABM-patients the association between NLR and elevated cerebral blood flow velocity(CBFv) remains unclear.Methods This study included all (CABM)-patients admitted to a German tertiary center between 2006-2016. Patient demographics, in-hospital measures and neuroradiological data were retrieved from institutional databases. CBFv was assessed by transcranial Doppler sonography transcranial doppler(TCD). Patients’, radiological and laboratory characteristics were compared between patients with/without elevated CBFv. Multivariate-analysis investigated parameters independently associated with elevated CBFv. Receiver operating characteristic(ROC-)curve analysis was undertaken to identify the best cut-off for NLR to discriminate between increased CBFv.Results108 patients with CABM were identified. 27.8%(30/108) showed elevated CBFv. These patients had a worse clinical status on admission(Glasgow Coma Scale:12[9-14 vs .14[11-15]; p=0.005) and required more often intensive care (30/30[100%]vs.63/78[80.8%];p=0.01).The causative pathogen was S. pneumoniae in 70%. These patients developed more often cerebrovascular complications with delayed cerebral ischemia(DCI) within hospital stay(p=0.031). A significantly higher admission-NLR was observed in patients with elevated CBFv(median[IQR]:elevated CBFv:24.0[20.4-30.2] vs . normal CBFv:13.5[8.4-19.5];p<0.001). After adjusting for significant parameters in univariate testing, NLR on admission was significantly associated with increased CBFv(Odds ratio[95%CI]:1.042[1.003-1.084];p=0.036). ROC-analysis identified a NLR of 20.9 as best cut-off value to discriminate between elevated CBFv(area under the curve=0.713, p<0.0001,Youden's Index=0.441;elevated CBFv:NLR > 20.9 19/34[55.9%] vs. NLR<20.9 11/74[14.9%];p<0.001).Conclusions Intracranial vascular complications are common among CABM-patients and are a risk factor for unfavorable outcome at discharge. NLR is independently associated with elevated CBFv.
... Datos concordantes fueron publicados en un meta análisis reciente, donde se concluye que los corticoides demostraron una menor mortalidad sólo en MBA por S. pneumoniae, pero no en N. meningitidis ni H. influenzae, ni se disminuyó la mortalidad global. Además, se demostró una reducción de secuelas neurológicas sólo en países desarrollados, pero no en los subdesarrollados (26). Los beneficios de su uso se observan solamente si se administra 20 minutos antes o concomitante a los antibióticos, pero no tiene utilidad en forma posterior al inicio de la antibióticoterapia. ...
Article
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La Meningitis Bacteriana Aguda (MBA) de adquisición comunitaria es una enfermedad prevalente en todo el mundo; constituye siempre una emergencia médica y se asocia a una alta morbimortalidad. Su epidemiología es variable y los principales agentes en adultos son S. pneumoniae, N. meningitidis, H. influenzae y L. monocitogenes. En Chile existe un sistema de vigilancia recientemente implementado que permitirá un mejor diagnóstico epidemiológico. Las manifestaciones clínicas clásicas no siempre están presentes principalmente en adultos mayores. El diagnóstico requiere del estudio de líquido cefalorraquídeo, y las técnicas de biología molecular han significado un aporte relevante en los últimos años. El tratamiento antibiótico debe ser instaurado rápidamente para mejorar el pronóstico, mientras que la terapia coadyuvante con corticoides en adultos tiene sólo beneficios en etiología neumocócica. Se requieren mejores estrategias de prevención frente a una entidad que no ha cambiado su mortalidad a pesar del progreso de la medicina moderna.
... The use of Dexamethasone has reduced mortality and severe hearing damage caused by ABM. This effect seems most pronounced in Pneumococcal meningitis in high-income countries [11][12][13][14][15][16] whereas adults in low-income countries, this adjunct therapy did not show a beneficial effect. A reduction in ICP may be achieved by sedation, hyperventilation, external CSF drainage, hypertonic saline, or decompressive craniotomy. ...
Article
Background: The aim of this study was to evaluate the clinical outcome of patients with severe bacterial meningitis where intracranial pressure (ICP) monitoring has been performed. Methods: A retrospective observational study including patients admitted 1st. January 2005 to 31st. December 2014. Thirty nine patients age 18–89 years were included. All the patients received intensive care with mechanical ventilation, ICP monitoring, sedation, antibiotics and corticosteroids according to current guidelines. Clinical outcome was defined as death during hospitalization or survival at hospital discharge. Results: The most common pathogen was Streptococcus pneumoniae (26; 67%). Thirteen patients died (33%) and neurologic impairment was noted in twenty two (84.6%) surviving patients. In S. pneumoniae cases patients with adverse outcome were significantly older (p = 0.0024) and immunosuppressed (p = 0.034). Lower mean-cerebral perfusion pressure (CPP) was found to correlate with adverse outcome (p = 0.005). Cerebrospinal fluid (CSF) was drained in fourteen patients. Increased ICP (>20 mmHg) was observed in twenty four patients. No significant correlation was found between measured ICP and head CT scans with signs of elevated ICP. Conclusions: Patients with severe meningitis should be admitted to intensive care units and evaluated for ICP monitoring regardless of head CT findings.
... One of the most common sequelae of bacterial meningitis with high impact on general functioning is hearing loss, either unilateral or bilateral, and varying from mild to profound. Timely administration of dexamethasone or other steroids, preferably before hearing loss, is diagnosed, generally reduces the risk of hearing loss (1). ...
Article
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Objective: Sensorineural hearing loss is a common sequela of bacterial meningitis. The objective of this study is to delineate the incidence and course of hearing loss after bacterial meningitis. Study design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Data of 655 patients who suffered from bacterial meningitis between 1985 and 2015 were analyzed. Interventions: None. Main outcome measurements: Availability of audiometric data, incidence of hearing loss, and onset and course of hearing loss. Results: In this cohort the incidence of hearing loss (>25 dB) was 28% (95% confidence interval 23-34%). The incidence of profound hearing loss (>80 dB) was 13% (95% confidence interval 10-18%). Normal hearing at the first assessment after treatment for meningitis remained stable over time in all these patients. In 19 of the 28 patients with diagnosed hearing loss, the hearing level remained stable over time. Hearing improved in six patients and deteriorated in two patients. One patient showed a fluctuating unilateral hearing loss. Conclusion: Audiological tests in patients with bacterial meningitis, especially children, should be started as soon as possible after the acute phase is over. As we found no deterioration of initial normal hearing after bacterial meningitis, repeated audiometry seems indicated only for those with diagnosed hearing loss at first assessment.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
Article
Corticosteroids are used as an adjunct to antibiotics in the treatment of bacterial meningitis in an attempt to attenuate the intrathecal inflammatory response and thereby reduce mortality and morbidity. The purpose of the present paper is to provide a review of clinical studies of corticosteroids in the treatment of bacterial meningitis. Relevant literature was found in PubMed, the Cochrane databases, and references in studies. Forty-four publications of relevance were identified, comprising 29 publications of randomised studies, 10 publications reporting either non- or quasi-randomised studies, and five reporting retrospective studies, and nine meta-analyses. Taken together, dexamethasone treatment may be associated with a lower mortality in adults and fewer neurological and auditory sequelae in adults and children from high-income countries, in particular in adults suffering from pneumococcal meningitis. In contrast, studies conducted in developing countries have yielded less favourable results.
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This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD004405. DOI: 10.1002/14651858.CD004405.pub2. Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary and Characteristics and Key Findings Tables articles. Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
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Conference Paper
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Les complications neurologiques graves de type myélite transverse et vascularite cérébrale au cours des méningites à Streptococcus pneumoniae sont rares. Nous rapportons 3 cas de complications neurologiques graves : 1 cas de myélite transverse et 2 cas de vascularite cérébrale postméningite à pneumocoque. La revue de la littérature retrouve 10 cas de myélite transverse et 30 cas de vascularite cérébrale. Cas 1 : Un homme de 58 ans a été hospitalisé pour méningite à S. pneumoniae et traité par ceftriaxone sans corticothérapie. L’amélioration clinique à J24 avait permis un transfert dans notre service en post-réanimation. À J28, il a présenté une paraplégie brutale. L’IRM médullaire a confirmé le diagnostic de myélite transverse (T3-T5) et un traitement de 5 jours par méthylprednisolone a permis une récupération neurologique partielle. Cas 2 : Une femme de 51 ans a été admise pour méningite à S. pneumoniae traitée par ceftriaxone sans corticothérapie. L’apyrexie et l’amélioration neurologique ont été observées à 24 heures d’antibiothérapie. À J3, une aggravation neurologique brutale avec signes de focalisation neurologique a nécessité un transfert en réanimation. À l’IRM cérébrale, une vascularite a été retrouvée. La patiente a pour séquelle un discret syndrome frontal. Cas 3 : Une femme de 67 ans a été admise après 48 heures de réanimation pour méningite à S. pneumoniae traitée par céfotaxime avec amélioration clinique. La dexaméthasone a été débutée à J2 pour 5 jours. À J13, l’apparition d’un trouble de la conscience nous a fait réaliser une angio-IRM cérébrale, retrouvant une thrombophlébite et une vascularite cérébrale. Les complications neurologiques à type de myélite transverse et de vascularite cérébrale sont rares. Un examen neurologique et une imagerie cérébrale répétés sont essentiels pour leurs diagnostics précoces. La corticothérapie n’a pas montré d’effet protecteur sur l’apparition.
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Bacterial meningitis continues to be an important disease throughout the world and can be a life-threatening emergency if not suspected, appropriately diagnosed and managed expeditiously. The epidemiology of bacterial meningitis has changed dramatically over the last 20 years, primarily as a result of the introduction of conjugate vaccines against the common meningeal pathogens, such that in the developed world where vaccination is routinely utilized, bacterial meningitis has become a disease of adults rather than of infants and children. The management approach to patients with suspected or proven bacterial meningitis includes emergent cerebrospinal fluid analysis and initiation of appropriate antimicrobial and adjunctive therapies. The choice of empirical antimicrobial therapy is based on the patient's age and underlying disease status; once the infecting pathogen is isolated, antimicrobial therapy can be modified for optimal treatment. Many patients with suspected or proven bacterial meningitis should also receive adjunctive dexamethasone therapy. This is based on experimental animal model data which demonstrated that the subarachnoid space inflammatory response that results from antimicrobial-induced bacterial lysis can contribute to morbidity and mortality. Clinical studies have demonstrated the benefit of adjunctive dexamethasone in infants and children with Haemophilus influenzae type B meningitis, and adults with pneumococcal meningitis, in which mortality and adverse outcome are reduced. Use of adjunctive dexamethasone in adults with meningitis caused by other bacteria, and in infants and children with pneumococcal meningitis, is controversial. To be effective, adjunctive dexamethasone should be administered concomitant with or just prior to the first antimicrobial dose for maximal effect on the subarachnoid space inflammatory response.
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