Week 3 – Dexamethasone in Bacterial Meningitis

“Dexamethasone in Adults With Bacterial Meningitis”

N Engl J Med 2002; 347:1549-1556 [NEJM free full text]

The current standard of care in the treatment of suspected bacterial meningitis in the developed world includes the administration of dexamethasone prior to or at the time of antibiotic initiation. The initial evaluation of this practice in part stemmed from animal studies which demonstrated that dexamethasone reduces CSF concentrations of inflammatory markers as well as neurologic sequelae after meningitis. RCTs in the pediatric literature also demonstrated clinical benefit. The best prospective trial in adults was this 2002 study by de Gans et al.

Population: adults with suspected meningitis

Intervention: dexamethasone 10mg IV q6hrs x4 days started 15-20 minutes before first IV abx

Comparison: placebo IV with same administration as above

Outcome:
primary = Glasgow Outcome Scale at 8 weeks (1 = death, 2 = vegetative state, 3 = unable to live independently, 4 = unable to return to school/work, 5 = able to return to school/work)
secondary = death, focal neurologic abnormalities, and others
subgroup analyses performed by organism

Results/Conclusion:
301 patients were randomized. At 8 weeks, 15% of dexamethasone patients had an unfavorable outcome (Glasgow Outcome Scale score of 1-4), vs. 25% of placebo patients (RR 0.59, 95% CI 0.37 – 0.94, p= 0.03). Among patients with pneumococcal meningitis, 26% of dexamethasone patients had an unfavorable outcome, vs. 52% of placebo patients. There was no significant difference among treatment arms within the subgroup of patients infected with meningococcal meningitis. Overall, death occurred in 7% of dexamethasone patients and 15% of placebo patients (RR 0.48, 95% CI 0.24 – 0.96, p = 0.04). In pneumococcal meningitis, 14% of dexamethasone patients died, vs. 34% of placebo patients. There was no difference in rates of focal neurologic abnormalities or hearing loss in either treatment arm (including within any subgroup).

Implication/Discussion:
Early adjunctive dexamethasone improves mortality in bacterial meningitis.

As noted in the above subgroup analysis, this benefit appears to be driven by the efficacy within the pneumococcal meningitis subgroup. Of note, the standard initial treatment regimen in this study was amoxicillin 2gm q4hrs for 7-10 days, not our standard ceftriaxone + vancomycin +/- ampicillin. Largely on the basis of this study alone, the IDSA guidelines for the treatment of bacterial meningitis (2004) recommend dexamethasone 0.15 mg/kg q6hrs for 2-4 days with first dose administered 10-20 min before or concomitant with initiation of antibiotics. Dexamethasone should be continued only if CSF Gram stain, CSF culture, or blood cultures are consistent with pneumococcus.

Further Reading:
1. IDSA guidelines for management of bacterial meningitis (2004)
2. Wiki Journal Club
3. 2 Minute Medicine

Summary by Duncan F. Moore, MD

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