Corticosteroids in adults with bacterial meningitis

1
Corticosteroids in adults with bacterial
meningitis

• Diederik van de Beek
• Department of Neurology
• Netherlands Reference laboratory for Bacterial
  Meningitis
• Center of infection and Immunity Amsterdam
  (CINIMA)
• Academic Medical Center
• Amsterdam
• D.vandeBeek_at_amc.uva.nl

2
Adjunctive dexamethasone

• Rationale of adjunctive dexamethasone
• Clinical data
• European Dexamethasone Study
• Meta-analysis 2004
• Meta-analysis Cochrane
• Vietnam and Malawi
• Side-effects
• 4 conclusions

3
Adjunctive dexamethasone

• Inflammation CNS outcome
• European clinical trial
• 301 adults with meningitis
• Dexamethasone (10 mg qid, 4d) vs placebo
• Started before/with first dose antibiotics

4
Flow of patients
5
Outcome
de Gans van de Beek N Engl J Med 2002
6
Adverse events
7
Meta-analysis 2004

• Adults with bacterial meningitis
• 5 randomized clinical trials on steroids
• 623 patients included
• 234 pneumococcal meningitis
• 232 meningococcal meningitis
• Death 12 vs. 22 odds ratio 0.6 (95CI
  0.40-0.81)

van de Beek et al Lancet Infect Dis 2004
8
Cochrane meta-analysis 2007

• gt2800 children and adults
• Beneficial effect of steroids
• Case fatality (RR 0.83, CI 0.71-0.99)
• Severe hearing loss (RR 0.65, CI 0.47-0.91)
• Neurological sequelae (RR 0.67, CI 0.45-1.00)
• No effect in low income countries

van de Beek et al Cochrane 2007
9
2007 RCTs in adults
10
Asian Trial

• Vietnam, randomized, double-blind,
  placebo-controlled
• Dexamethasone 0.8 mg/kg/d, 4 days
• 435 adults with suspected bacterial meningitis
• Definitive bacterial meningitis 69
• HIV positive lt1
• Pre-treated with antibiotics 63

11
Asian Trial

• S. suis meningitis (26)
• Pretreatment antibiotics treatment effect
  (P0.84)

RR 0.79, CI 0.45-1.39
RR 0.43, CI 0.20-0.98
12
African Trial

• Malawi, randomized, double-blind,
  placebo-controlled
• Dexamethasone 32 mg/d, 4 days
• 465 adults with bacterial meningitis
• HIV-positive gt90 (median CD4 cell count 102/mm3)
• pre-treated with antibiotics 40

13
African Trial

• Pneumococcal meningitis (55)
• High mortality (54)
• Effect dexamethasone on mortality OR 1.14, CI
  0.79-1.64
• No effect in subgroups

14
Penetration of vancomycin

• Dexamethasone may impede CSF penetration
• Vancomycin 60mg/kg/day dexamethasone 0.6
  mg/kg/day
• 10 children and 13 adults with pneumococcal
  meningitis
• Serial lumbar punctures
• Sufficient CSF penetration of vancomycin

Klugman et al Antimicrob Agents Chemoth 1995,
Richard et al Clin Infect Dis 2007
15
Neuropsychological outcome

• DXM may cause hippocampal damage
• Follow-up European trial
• Neuropsychological outcome
• 88 of eligible patients
• No differences between DXM and placebo groups

Weisfelt et al Ann Neurol 2006
16
Conclusions

• Suspected or proven community-acquired bacterial
  meningitis
• Dexamethasone 10 mg IV before or with first dose
  of antibiotic
• Low dose or no steroids if
• Septic shock
• No dexamethasone if
• Pre-treatment with parenteral antibiotics
• HIV-positive or low-income countries
• Recent head injury
• CSF shunt
• 4 day treatment 40 mg/day

van de Beek et al N Engl J Med 2006
17
Corticosteroids in adults with bacterial
meningitis

• Diederik van de Beek
• Department of Neurology
• Netherlands Reference laboratory for Bacterial
  Meningitis
• Center of infection and Immunity Amsterdam
  (CINIMA)
• Academic Medical Center
• Amsterdam
• D.vandeBeek_at_amc.uva.nl