1. Current Evidence of Corticosteroids for acute bacterial meningitis - have benefit or not? -

2. 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

3. 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

4. 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

5. Clinical problem
Dose steroid had benefit in acute meningitis ?

6. PICO P: Acute meningitis I : Steroid treatment C: No steroid treatment
O: outcome (neurologic sequels, mortality…)

7. Database
Pubmed
Cochrane library

8. Keywords
Steroid
Meningitis

9. Keyward adjust by MeSH categories

10. Keyward adjust by MeSH categories

11. Search

13. Limitation

15. 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"

16. Further selection: 75 items
Search result: items
Further selection: 75 items
16 full text
2 Cochrane library review

17. Corticosteroids for acute bacterial meningitis
Cochrane review level 1a

18. Corticosteroids for acute bacterial meningitis -Cochrane review level 1a

19. Corticosteroids for acute bacterial meningitis -Cochrane review level 1a

20. Corticosteroids for acute bacterial meningitis -Cochrane review level 1a

21. Corticosteroids for acute bacterial meningitis -Cochrane review level 1a

22. Corticosteroids for managing tuberculous meningitis
Cochrane review level 1a

23. Corticosteroids for tuberculosis meningitis -Cochrane review level 1a

24. Corticosteroids for tuberculosis meningitis -Cochrane review level 1a

25. Corticosteroids for tuberculosis meningitis -Cochrane review level 1a

26. Corticosteroids for tuberculosis meningitis -Cochrane review level 1a

27. 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:

28. Dexamethasone as Adjunctive Therapy in Bacterial Meningitis Level 2a

29. Dexamethasone as Adjunctive Therapy in Bacterial Meningitis Level 2a

30. Dexamethasone as Adjunctive Therapy in Bacterial Meningitis Level 2a

31. 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

32. Dexamethasone therapy for bacterial meningitis in adults Level 2b

33. 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:

34. Corticosteroids for Bacterial Meningitis in Adults in Sub-Saharan Africa Level 1c

35. Corticosteroids for Bacterial Meningitis in Adults in Sub-Saharan Africa Level 1c

36. Dexamethasone in Adults with Bacterial Meningitis
Prospective, randomized, double-blind, multicenter trial Level 1b
N Engl J Med 2002; Vol. 347:

37. Dexamethasone in Adults with Bacterial Meningitis Level 1b

38. Dexamethasone in Adults with Bacterial Meningitis Level 1b

39. 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

40. Dexamethasone and Bacterial Meningitis Level 1c

41. Dexamethasone and Bacterial Meningitis Level 1c

42. Dexamethasone and Bacterial Meningitis Level 1c

43. 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:

44. Dexamethasone for the Treatment of Tuberculous Meningitis in Adolescents and Adults Level 1b

45. Dexamethasone for the Treatment of Tuberculous Meningitis in Adolescents and Adults Level 1b

46. 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:

47. Dexamethasone in Vietnamese Adolescents and Adults with Bacterial Meningitis Level 1b

48. 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

49. Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis Level 5

50. Summary 1 Papulation Benefit Level All patients, Outcome : Mortalityno 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

51. 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

52. 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