Acute bacterial meningitis is an infection of the meninges (the system of membranes which envelops the brain and spinal cord) that often causes hearing loss. Bacterial meningitis is fatal in 5% to 40% of children and 20% to 50% of adults despite treatment with adequate antibiotics. It is caused by bacteria that usually spread from an ear or respiratory infection and is treated with antibiotics. Corticosteroids are drugs that can reduce the inflammation caused by infection. This inflammation has been shown to aggravate damage to the nervous system in experimental meningitis studies in animals. Research on the use of corticosteroids in addition to antibiotics has had conflicting results. This review of 25 trials, including 4121 participants, found that the corticosteroid dexamethasone leads to a reduction in hearing loss and other neurological sequelae in participants in high-income countries who have bacterial meningitis, but is not effective in low-income countries. An analysis for different bacteria causing meningitis showed that patients with meningitis due to Streptococcus pneumoniae (S. pneumoniae) treated with corticosteroids had a lower death rate, while no effect on mortality was seen in patients with Haemophilus influenzae (H. influenzae) and Neisseria meningitidis (N. meningitidis) meningitis. Corticosteroids decreased the rate of hearing loss in children with meningitis due to H. influenzae, but not in children with meningitis due to other bacteria. Dexamethasone increased the rate of recurrent fever but was not associated with other adverse events.
Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries.
In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.
To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis.
We searched CENTRAL 2012, Issue 12, MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), Web of Science (2010 to January 2013), CINAHL (2010 to January 2013) and LILACS (2010 to January 2013).
Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis.
We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality.
Twenty-five studies involving 4121 participants were included. Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P = 0.07). A similar non-significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).
Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) or Neisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.
In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.
Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies.
Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events.