Dexamethasone In Adults With Bacterial Meningitis

De Gans J, Van De Beek D. NEJM NOV 14 2002; 347(20): 1549-56.

RESULTS

Randomization: 301 enrolled, 157 to the dexamethasone group, 144 to the placebo group. Intention to treat analysis. In the dexamethasone group, 11 withdrawn, 3 lost to follow-up. In the placebo group, 11 withdrawn, 4 lost to follow-up.

Baseline: headache (94%), fever (81%), neck stiffness (94%). Positive gram stain in 215 patients (74%), positive cultures in 234 patients (78%).

Primary Outcome: Unfavorable Outcome

All patients: ARR 10%, NNT 10, p = 0.03
S. pneumo: ARR 26%, NNT 3.8, p = 0.006
N. meningitidis: ARR 3%, NNT 33, p = 0.74
Other bacteria: ARR -11%, NNH 9, p = 0.55

Secondary Outcome: Death

All patients: 7% vs 15%, ARR 8%, NNT 12.5, p = 0.04
S. pneumo: 14% vs 34%, ARR 20%, NNT 5, p = 0.02
N. men: 4% vs 2%, ARR -2%, NNH 50, p = 1.00

table 2

Adverse Events: no significant difference in GI bleeding, hyperglycemia, herpes zoster, or fungal infections.

METHODS

Study Type: prospective, randomized, double-blind, multicenter trial vs placebo

Inclusion: (a) 17y + & (b) suspected meningitis with cloudy CSF, bacteria in CSF on gram stain, or CSF leukocyte count > 1000/mm3.

Exclusion: (a) h/o hypersensitivity to beta-lactam ABx or corticosteroids, (b) pregnant, (c) CSF shunt, (d) treated with oral or IV ABx in last 48h, (e) h/o active TB or fungal infection, (f) recent h/o head trauma, neurosurgery, or PUD, or (g) enrolled in another trial

Time Frame: June 1993 to December 2001

Treatment: (1) Dexamethasone 10 mg IV q6h for four days versus (2) placebo. Treatment given 15-20 minutes before IV ABx, but after interim analysis, amended to allow treatment to be given concurrently with antibiotics. Antibiotic given was amoxicillin 2 g IV q4h for 7-10 days (Netherlands).

Primary Outcome: score on Glasgow Outcome Scale 8 weeks after randomization. Unfavorable outcome is a score of 1-4/5. A score of 1 = death, 2 = vegetative state, 3 = severe disability, 4 = moderated disability, 5 = mild or no disability.

Secondary Outcome: (1) death, (2) focal neurologic abnormalities (aphasia, cranial-nerve palsy, monoparesis, hemiparesis, and severe ataxia), (3) hearing loss, (4) GI bleeding, (5) fungal infection, (6) herpes zoster, (7) hyperglycemia (blood glucose > 144 mg/dL [8.0 mmol/L]).

Predefined Subgroup Analysis: Neisseria meningitidis, Streptococcus pneumoniae, other bacteria, and an unidentified cause.

ADDITIONAL READING

Nguyen TH. Dexamethasone in Vietnamese Adolescents and Adults with Bacterial Meningitis. NEJM Dec 13 2007; 357(24): 2431-40.

Scarborough M. Corticosteroids for Bacterial Meningitis in Adults in Sub-Saharan Africa. NEJM Dec 13 2007; 357(24); 2441-50.

Thomas R. Trial of dexamethasone treatment for severe bacterial meningitis in adults. Intensive Care Med 1999; 25: 475-80.

Girgis NI. Dexamethasone treatment for bacterial meningitis in children and adults. Pediat Infect Dis J 1989; 8: 848-51.