Morbidity and mortality rates are high among adult patients with acute bacterial meningitis especially those with pneumococcal meningitis. Animal studies have shown that bacterial lysis occuring with antibiotic treatment leads to inflammation in the subarachnoid space and that treatment with dexamethasone, an anti-inflammatory agent, reduced cerebrospinal fluid inflammation and neurologic sequelae (Tauber, et al., J Infect Dis., PMID 3973406).

Controlled trials have aimed to determine whether providing adjuvant corticosteroid therapy is beneficial in children with acute bacterial meningitis. McIntyre, et al., showed that giving dexamethasone reduced severe hearing loss hearing loss in children with haemophilus influenzae type B meningitis (PMID 9302246). His study also showed that giving dexamethasone prior to, or at the same time as, antibiotics can protect against hearing loss in children with pneumococcal meningitis (PMID 9302246).

Prior to this study, there was limited data to guide the use of adjunctive dexamethasone therapy in adults with bacterial meningitis.

Clinical Question

Does adjunctive dexamethasone treatment improve outcomes in adult patients with acute bacterial meningitis compared to standard antibiotic therapy alone?


Adults in five European countries over a period of nine years (from June 1993 to December 2001)

  • 17 years of age or older
  • Suspected meningitis
  • Cloudy CSF, bacteria in CSF on Gram staining or a CSF leukocyte count >1000/mm³


Dexamethasone sodium phosphate (Oradexon)

  • 10mg IV q6 hours for four days
  • Administered 15-20 minutes before,or at the same time as, IV antibiotic administration


Placebo identical in appearance to the active drug


Primary outcome: score on the Glasgow Outcome Scale eight weeks after randomization, as assessed by the patient’s physician

  • Favorable outcome defined by a score of 5; Unfavorable outcome defined by a score of 1-4
    • 1 = Death
    • 2 = A vegetative state (the patient is unable to interact with the environment)
    • 3 = Severe disability (the patient is unable to live independently but can follow commands)
    • 4 = Moderate disability (the patient is capable of living independently but unable to return to work or school)
    • 5 = Mild or no disability (the patient is able to return to work or school)
  • Secondary outcomes: Death, focal neurologic abnormalities (aphasia, severe ataxia, cranial nerve palsy, monoparesis, hemiparesis), hearing loss, GI bleeding (clinically relevant with a drop in Hg level), fungal infection, herpes zoster, hyperglycemia
  • Subgroup analyses were performed for patients with prospectively defined causes of meningitis: streptococcus pneumoniae and Neisseria meningitidis


Multicenter, double-blind, parallel group, randomized, placebo-controlled trial

  • N = 301; Dexamethasone N = 157, Placebo N = 144


  • History of hypersensitivity to beta lactam antibiotics or corticosteroids
  • Pregnant women
  • History of a CSF shunt
  • Treatment with oral/IV antibiotics in the previous 48h
  • History of active TB or fungal infection
  • History of recent head trauma, neurosurgery or PUD
  • Enrolled in another trial

Primary Results

Unfavorable outcome

  • All patients
    • Dexamethasone 23/157 (15%)
    • Placebo 36/144 (25%)
  • Streptococcus pneumoniae
    • Dexamethasone 15/58 (26%)
    • Placebo 26/50 (52%)
  • Neisseria meningitidis
    • Dexamethasone 4/50 (8%)
    • Placebo 5/47 (11%)

Secondary Outcomes

  • Death
    • All patients
      • Dexamethasone 11/157 (7%)
      • Placebo 21/144 (15%)
    • Streptococcus pneumoniae
      • Dexamethasone 8/58 (14%)
      • Placebo 17/50 (34%)
    • Neisseria meningitidis
      • Dexamethasone 2/50 (4%)
      • Placebo 1/47 (2%)
    • Focal neurologic abnormalities
      • All patients
        • Dexamethasone 18/143 (13%)
        • Placebo 24/119 (20%)
      • Streptococcus pneumoniae
        • Dexamethasone 11/49 (22%)
        • Placebo 11/33 (33%)
      • Neisseria meningitidis
        • Dexamethasone 3/46 (7%)
        • Placebo 5/44 (11%)
      • Hearing loss
        • All patients
          • Dexamethasone 13/143 (9%)
          • Placebo 14/119 (12%)
        • Streptococcus pneumoniae
          • Dexamethasone 7/49 (14%)
          • Placebo 7/33 (21%)
        • Neisseria meningitidis
          • Dexamethasone 3/46 (7%)
          • Placebo 5/44 (11%)

Critical Findings

  • Primary:
    • Proportion of patients with an unfavorable outcome significantly smaller in dexamethasone group than in the placebo group
    • Unfavorable outcomes occurred in 15% of patients in the dexamethasone group compared to 25% in the placebo group with a relative risk of 0.59 (p = .03)
    • Patients in dexamethasone group were 41% less likely to develop an unfavorable outcome compared to the placebo group
    • Absolute risk reduction of an unfavorable outcome was 10%
    • Among the subgroup of patients with pneumococcal meningitis, unfavorable outcomes occurred in 26% of patients compared to 52% in the placebo group with a relative risk of 0.50 (p = .006)
    • Patients with pneumococcal meningitis were 50% less likely to develop an unfavorable outcome if they received dexamethasone
    • Dexamethasone did not provide a significant benefit to those with Neisseria meningitidis
    • Significant predictors of an unfavorable outcome:
      • Coma on admission (P=0.002)
      • Hypotension (P=0.03)
      • Meningitis due to S. pneumoniae (P=0.02)
  • Secondary Results:
    • Proportion of patients who died was significantly smaller in the dexamethasone group than in the placebo group (7% 15%; relative risk of 0.48, p = 0.04)
    • Patients in the dexamethasone group were 52% less likely to die
    • Absolute risk reduction of death with administration of dexamethasone was 8% and 20% in patients with pneumococcal meningitis
    • Adjuvant treatment with dexamethasone did not have a significant beneficial effect on neurologic sequelae, including hearing loss
  • Other significant findings:
    • Proportion of patients with impairment of consciousness (18 of 157 patients [11%] 36 of 144 [25%], p=0.002), seizures (8 [5%] vs. 17 [12%], p =0.04) and cardiorespiratory failure (16 [10%] vs. 29 [20%], p=0.02) was significantly less in patients who received dexamethasone compared to placebo
    • Dexamethasone appeared to be most beneficial in patients with moderate or severe disease as assessed by GCS score on admission


  • Randomized, double blind study
  • Multicenter study
  • Use of a well-validated scale with good interobserver agreement (Glasgow Outcome Scale)
  • Of 301 patients, only 7 were lost to follow up; however, there was use of last observation carried forward analysis


  • Treatment may have been delayed in patients who required CT before LP, and inclusion of patients in the study depended on the presence of CSF abnormalities
  • Only 72% of pneumoniae samples were submitted for susceptibility testing; all the isolates were susceptible to penicillin, a finding that is unusual in many areas of the world

Author's Conclusions

“Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis. Adjunctive treatment with dexamethasone reduced the risks of both an unfavorable outcome and death. Dexamethasone did not have a beneficial effect on neurologic sequelae, including hearing loss. However, neurologic sequelae were seen predominantly in the most severely ill patients, and the proportion of severely ill patients who survived to be tested was larger in the dexamethasone group than in the placebo group. The beneficial effect of dexamethasone was most apparent in the patients with pneumococcal meningitis. However, a beneficial effect in the patients with meningococcal meningitis cannot be ruled out, since the number of patients in this subgroup was small. Therefore, we recommend dexamethasone treatment for all patients with acute bacterial meningitis.”

Our Conclusions

  • Early administration of dexamethasone improves outcomes in adult patients with acute bacterial meningitis
  • Dexamethasone reduced the risk of both unfavorable outcomes and death, but did not have a beneficial effect on neurologic sequelae

Bottom Line

Dexamethasone therapy is warranted in adults suspected of having acute bacterial meningitis, especially those suspected of having pneumococcal meningitis. Dexamethasone should be given with or just before the first dose of antibiotics.