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Three Part Question

In [adults with community acquired bacterial meningitis]does [the early administration of corticosteroids] [reduce mortality and long term neurological or audiological sequelae]?

Clinical Scenario

An 18 year old student is brought to the Emergency Department having been found collapsed in her room. She had been seen by her friends earlier in the day, when she reported that she had a severe headache. On examination, she is found to have a temperature of 38.40C, a GCS of 12 (E3 M6 V3) and slight neck stiffness. She is noted to be more settled with the lights out. There is no papilloedema and no focal neurological signs. You make an initial diagnosis of bacterial meningitis, but in view of the depressed level of consciousness request a CT Brain before lumbar puncture is carried out. This will take at least one hour to be organised, and in the meantime, you decide to proceed with intravenous ceftriaxone. You are unsure whether she would benefit from the administration of dexamethasone prior to her antibiotics.

Search Strategy

• Medline database (Ovid interface) 1966 – April 2003:
{(Exp meningitis, meningococcal/ or exp meningitis, pneumococcal/ or exp meningitis, bacterial/) and [(exp adrenal cortex hormones/ or corticosteroids.mp.) or exp glucocorticoids/ or exp dexamethasone/ or exp prednisolone/ or exp prednisone/ or exp hydrocortisone/ or exp methylprednisolone/] and maximally sensitive RCT filter} Limit to human and English language and all adult<19 plus years>
• Embase database (Ovid interface) 1980 – Dec 2003: {Exp bacterial meningitis/ and (exp corticosteroid therapy/ or exp corticosteroid/ or exp glucocorticoid/ or exp dexamethasone/ or exp prednisolone/ or exp prednisone/ or exp methylprednisolone/ or exp hydrocortisone/) Limit to human and English language

Search Outcome

32 papers identified from Medline search of which 2 were concerned with adults and answered the 3 part question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
de Gans et al 2002 Netherlands	301 adults with CSF confirmed meningitis allocated to amoxicillin and placebo, or dexamethasone given prior to antibiotics	Prospective randomised controlled trial	Glasgow outcome scale at 8 weeks (score 5 favourable, score 1-4 unfavourable)	Better in treatment group (RR 0.59, 95% CI 0.37 – 0.94). Effect seen only with strep pneumoniae.	Change of protocol to give antibiotics and steroids together during course of trial rather than steroids first. Change of protocol to give locally recommended antibiotic during trial.
			Mortality	Reduced in treatment group (RR 0.48, 95% CI 0.24 – 0.96). Effect seen only with strep pneumoniae
			Focal neurological abnormalities	No difference
			Hearing loss	No difference
Thomas et al 1999 France/ Switzerland	60 adults with CSF confirmed meningitis allocated to dexamethasone or placebo, plus amoxycillin	Prospective randomised controlled trial	Cure without neurological sequelae	No difference	Trial halted before sufficient numbers could be recruited due to change in recommended antibiotic regime

Comment(s)

Bacterial meningitis in adults is usually due to strep. pneumoniae or neisseria meningitidis. Many previous studies have been performed in children with a high prevalence of haemophilus influenzae meningitis, suggesting a reduction in adverse events with pre-antibiotic steroids. Although the study by de Gans would suggest that this benefit also extends to adult patients with a different spectrum of organisms, the benefit was only seen in patients with pneumococcal meningitis.

Clinical Bottom Line

In patients who are well enough to undergo a lumbar puncture prior to the administration of antibiotics, steroids would seem to confer benefit. However, for sicker patients with possible alternative diagnoses, the risk of steroids must be balanced against the possible benefits.

References

1. de Gans J, van de Beek D Dexamethasone in adults with bacterial meningitis N Engl J Med 2002;347(20):1549-1556
2. Thomas R, Le Tulzo Y, Bouget J, Camus C, Michelet C, Le Corre P, Bellisant E Trial of dexamethasone treatment for severe bacterial meningitis in adults Intensive Care Med 1999;25(5):475-480