Classic Literatue
Dexamethasone in Adults with Bacterial Meningitis
de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. N Engl J Med. 2002 Nov14;347(20):1549-1556.
Background
The mortality and morbidity associated with acute bacterial meningitis among adults is high. Studies in animals have demonstrated that antibiotics cause a profound inflammatory response in the subarachnoid space due to bacterial lysis, and adjuvant treatment with an anti-inflammatory agent, such as dexamethasone, reduces cerebrospinal inflammation and neurologic sequelae. A meta-analysis of randomized controlled trials demonstrated the beneficial effects of adjunctive dexamethasone in children with bacterial meningitis, but there are few data on the use of dexamethasone in adults with bacterial meningitis. The authors of this study conducted a randomized, placebo-controlled, double-blind study to determine whether adjunctive dexamethasone treatment improves outcomes in adults with bacterial meningitis.
Methods
Patients from five northern European countries were enrolled in the study if they were suspected of having bacterial meningitis combined with one or more of the following cerebrospinal fluid (CSF) abnormalities: cloudy CSF, bacteria in CSF on Gram’s staining, or CSF leukocyte count >1,000/mm3. Patients were randomly assigned to receive either 10 mg of dexamethasone every six hours intravenously for four days or a placebo. Dexamethasone was given either 15–20 minutes before or with the first dose of antibiotics. All patients initially received two grams of amoxicillin intravenously every four hours, and all were treated for a total of seven to 10 days with antibiotics. The primary outcome measure was the patient’s score on the Glasgow Outcome Scale eight weeks after randomization; the secondary outcome measures were death, focal neurologic abnormalities, hearing loss, gastrointestinal bleeding, fungal infection, herpes zoster, and hyperglycemia.
Results
A total of 301 patients were enrolled in the study—157 in the dexamethasone group and 144 in the placebo group. Eight weeks after enrollment, the patients in the dexamethasone group had significantly fewer unfavorable outcomes as compared with the placebo group (15% versus 25%, P=0.03). The benefit was statistically significant only in the patients with meningitis due to S. pneumoniae (26% versus 52%, P=0.006). The overall percentage of deaths was significantly less in the dexamethasone group than in the placebo group (7% versus 15%, P=0.04), and this mortality benefit was most obvious in the patients with pneumococcal meningitis who had received dexamethasone instead of placebo (14% versus 34%, P=0.02). The other secondary outcome measures were not significantly different between the two groups.
Conclusions
Early adjunctive treatment with dexamethasone reduced the risks of both an unfavorable outcome and death in adults with acute bacterial meningitis. The beneficial effects of dexamethasone were most apparent in the patients with pneumococcal meningitis, but a beneficial effect in patients with meningococcal meningitis cannot be excluded. Given these findings, all adult patients with suspected acute bacterial meningitis should receive 10 mg of intravenous dexamethasone either before or with the first dose of antibiotics, and if bacterial meningitis is ruled in, 10 mg of dexamethasone should be given every six hours for a total of four days. TH