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

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 (95%CI )
van de Beek et al Lancet Infect Dis 2004

8. Cochrane meta-analysis 2007
>2800 children and adults
Beneficial effect of steroids
Case fatality (RR 0.83, CI )
Severe hearing loss (RR 0.65, CI )
Neurological sequelae (RR 0.67, CI )
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 <1%
Pre-treated with antibiotics 63%

11. Asian Trial S. suis meningitis (26%)
Pretreatment antibiotics ~ treatment effect (P=0.84)
RR 0.79, CI
RR 0.43, CI

12. African Trial Malawi, randomized, double-blind, placebo-controlled
Dexamethasone 32 mg/d, 4 days
465 adults with bacterial meningitis
HIV-positive >90% (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
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