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@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 (95%CI 0.40-0.81) 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 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 <1% • Pre-treated with antibiotics 63%

11. Asian Trial • S. suis meningitis (26%) • Pretreatment antibiotics ~ treatment effect (P=0.84) 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 >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 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@amc.uva.nl