Current Evidence of Corticosteroids for acute bacterial meningitis - have benefit or not? -
Bacterial meningitis was uniformly lethal up to the introduction of antimeningococcal antisera in the early 20th century In 1940, mortality rates were further reduced to approximately 20% with the introduction of penicillin Since the 1980s, experimental studies have unraveled pathogenesis and pathophysiological mechanisms in bacterial meningitis
The inflammatory response in the subarachnoid space was found to be associated with unfavorable outcome In these experiments, corticosteroids, and in particular dexamethasone, were able to reduce the inflammatory cascades in the subarachnoid space This led to clinical trials of dexamethasone as adjuvant therapy
Children with H. influenzae meningitis conducted in the early 1990s, dexamethasone reduced the frequency of neurologic sequels, but did not change mortality But mortality among included children was low (<1%) So the role of dexamethasone in the treatment of bacterial meningitis has remained controversial, especially in other papulation and pathogens
Clinical problem Dose steroid had benefit in acute meningitis ?
PICO P: Acute meningitis I : Steroid treatment C: No steroid treatment O: outcome (neurologic sequels, mortality…)
Database Pubmed Cochrane library
Keywords Steroid Meningitis
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Limitation
Oxford Centre for Evidence-based Medicine Levels of Evidence Therapy/Prevention, Aetiology/Harm Prognosis 1a SR (with homogeneity*) of RCTs SR (with homogeneity*) of inception cohort studies; CDR† validated in different populations 1b Individual RCT (with narrow Confidence Interval‡) Individual inception cohort study with > 80% follow-up; CDR† validated in a single population 1c All or none§ All or none case-series 2a SR (with homogeneity*) of cohort studies SR (with homogeneity*) of either retrospective cohort studies or untreated control groups in RCTs 2b Individual cohort study (including low quality RCT; e.g., <80% follow-up) Retrospective cohort study or follow-up of untreated control patients in an RCT; Derivation of CDR† or validated on split-sample§§§ only 2c "Outcomes" Research; Ecological studies "Outcomes" Research 3a SR (with homogeneity*) of case-control studies 3b Individual Case-Control Study 4 Case-series (and poor quality cohort and case-control studies§§) Case-series (and poor quality prognostic cohort studies***) 5 Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles"
Further selection: 75 items Search result: 193 items Further selection: 75 items 16 full text 2 Cochrane library review
Corticosteroids for acute bacterial meningitis Cochrane review level 1a
Corticosteroids for acute bacterial meningitis -Cochrane review level 1a
Corticosteroids for acute bacterial meningitis -Cochrane review level 1a
Corticosteroids for acute bacterial meningitis -Cochrane review level 1a
Corticosteroids for acute bacterial meningitis -Cochrane review level 1a
Corticosteroids for managing tuberculous meningitis Cochrane review level 1a
Corticosteroids for tuberculosis meningitis -Cochrane review level 1a
Corticosteroids for tuberculosis meningitis -Cochrane review level 1a
Corticosteroids for tuberculosis meningitis -Cochrane review level 1a
Corticosteroids for tuberculosis meningitis -Cochrane review level 1a
Dexamethasone as Adjunctive Therapy in Bacterial Meningitis: Meta-analysis of Randomized Clinical Trials -Searched by means of databases of the National Library of Medicine (MEDLINE, HEALTHLINE, and AIDSLINE) with the Medical Subject Headings "dexamethasone" and "meningitis" in English - Randomized, concurrently controlled trials of dexamethasone therapy in childhood bacterial meningitis. Nonrandomized studies were eligible for assessment of adverse effects of dexamethasone therapy Level 2a JAMA.1997;278:925-931
Dexamethasone as Adjunctive Therapy in Bacterial Meningitis Level 2a
Dexamethasone as Adjunctive Therapy in Bacterial Meningitis Level 2a
Dexamethasone as Adjunctive Therapy in Bacterial Meningitis Level 2a
Dexamethasone therapy for bacterial meningitis in adults Double blind placebo control study Patients were randomly assigned to receive either placebo (n=20) or dexamethasone (n=20) in addition to injection ceftriaxone 100 mg/kg/day (maximum 4 gm/day) for 14 days Level 2b Neurol India 2002;50:63
Dexamethasone therapy for bacterial meningitis in adults Level 2b
Corticosteroids for Bacterial Meningitis in Adults in Sub-Saharan Africaf Randomized, double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4 days) -Open-label trial of intramuscular versus intravenous ceftriaxone (2 g twice daily for 10 days) in adults with an admission diagnosis of bacterial meningitis in Blantyre, Malawi Total of 465 patients, 90% of whom were HIV-positive, were randomly assigned to receive dexamethasone (233 patients) or placebo (232 patients) Level 1c N Engl J Med 2007;357:2441-50
Corticosteroids for Bacterial Meningitis in Adults in Sub-Saharan Africa Level 1c
Corticosteroids for Bacterial Meningitis in Adults in Sub-Saharan Africa Level 1c
Dexamethasone in Adults with Bacterial Meningitis Prospective, randomized, double-blind, multicenter trial Level 1b N Engl J Med 2002; Vol. 347: 1549-56
Dexamethasone in Adults with Bacterial Meningitis Level 1b
Dexamethasone in Adults with Bacterial Meningitis Level 1b
Dexamethasone and Bacterial Meningitis A Meta-analysis of Randomized Controlled Trials MEDLINE search was conducted. MEDLINE was accessed for the period from January 1989, the year the previous meta-analysis” was published Criteria for inclusion were that the study was randomized and controlled and that it assessed the use of dexamethasone as adjunctive therapy in the treatment of bacterial meningitis in children Level 1c WestJ Med 1992 Jul; 157:27-31
Dexamethasone and Bacterial Meningitis Level 1c
Dexamethasone and Bacterial Meningitis Level 1c
Dexamethasone and Bacterial Meningitis Level 1c
Dexamethasone for the Treatment of Tuberculous Meningitis in Adolescents and Adults Randomized, double-blind, placebo-controlled trial Total of 545 patients were randomly assigned to groups that received either dexamethasone (274 patients) or placebo (271 patients). Only 10 patients (1.8 percent) had been lost to follow-up at nine months of treatment. Level 1b N Engl J Med 2004;351:1741-51
Dexamethasone for the Treatment of Tuberculous Meningitis in Adolescents and Adults Level 1b
Dexamethasone for the Treatment of Tuberculous Meningitis in Adolescents and Adults Level 1b
Dexamethasone in Vietnamese Adolescents and Adults with Bacterial Meningitis Randomized, double-blind, placebo-controlled trial - 435 patients over the age of 14 years who had suspected bacterial meningitis -Level 1b N Engl J Med 2007;357:2431-40
Dexamethasone in Vietnamese Adolescents and Adults with Bacterial Meningitis Level 1b
Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis Kinetics of cerebrospinal fluid (CSF) MMP and tissue inhibitors of MMPs (TIMPs) concentrations were studied in a subset of HIV uninfected adults (n = 37) with TBM recruited to a randomized, placebocontrolled trial of adjuvant dexamethasone Level 5 PLoS ONE 4(9): e7277, July 21, 2009
Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis Level 5
Summary 1 Papulation Benefit Level All patients, Outcome : Mortality no 1a All patients, Outcome : Severe hearing loss + All patients, Outcome : Short-term neurological sequelae All patients, Outcome : Long-term neurological sequelae All patients, Outcome : Adverse events Children, Outcome : Mortality Children, Outcome : Severe hearing loss Adults, Outcome : Mortality ++ Adults, Outcome : Short-term neurological sequelae
Summary 2 Pathogens Benefit Level Haemophilus influenzae, children, mortality no 1a Neisseria meningitidis, Children, mortality Streptococcus pneumoniae, Children, mortality ++ Non-Haemophilus influenzae, children, hearing loss No Haemophilus influenzae, children, hearing loss GNB, Children, mortality No data GNB, Children, hearing loss
Summary 3 Pathogens Benefit Level Haemophilus influenzae, adult, mortality no 1b Neisseria meningitidis, adult, mortality Streptococcus pneumoniae, adult, mortality ++ Non-Haemophilus influenzae, adult, hearing loss Haemophilus influenzae, adult, hearing loss GNB, adult, mortality No data GNB, adult, hearing loss