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Dexamethasone

The use of adjunctive dexamethasone (0.15 mg/kg per dose q6h for 2-4 d) decreases hearing loss and neurologic sequelae in children and infants with meningitis caused by HIB. The studies that support this largely have been carried out during the era when HIB was the most common meningeal pathogen. Controversy surrounds the administration of dexamethasone, which is given with or just before antibiotics.^[25] Dexamethasone may interrupt the cytokine-mediated neurotoxic effects of bacteriolysis, which are at maximum in the first days of antibiotic use.

A meta-analysis of 10 years of clinical trials confirmed that dexamethasone decreases morbidity, especially incidence and severity of neurosensory hearing loss, for H influenzae meningitis and suggested comparable benefit for S pneumoniae meningitis in childhood. No adequate adult studies exist, although the pathophysiology is presumably similar. Meta-analysis suggests that limiting dexamethasone therapy to 2 days may be optimal. Studies conducted in Europe have continued to support the use of dexamethasone in developed (as opposed to developing) countries, perhaps related to the relative incidence of TB meningitis.

Theoretically, anti-inflammatory effects of steroids decrease blood-brain barrier permeability and impede penetration of antibiotics into CSF. Decreased CSF levels of vancomycin have been confirmed in steroid-treated animals but not in human studies. Many authorities believe that all other antibiotics achieve minimal inhibitory concentrations (MICs) in CSF regardless of steroid use. Dexamethasone may not clinically impede even vancomycin.

More recent studies indicate that adjunctive steroids are also beneficial in the treatment of meningitis caused by bacterial pathogens other than HIB. In a large cohort of patients with acute meningitis due to pneumococcus, meningococcus, and other bacteria, the administration of adjunctive dexamethasone was significantly associated with a reduction in mortality and other unfavorable outcomes. The benefit was most apparent in cases due to pneumococcus.

The recent accumulation of scientific evidence about the benefits of steroid use suggests that it should be considered as adjunctive treatment in most adult patients in whom acute bacterial meningitis is suspected.

The timing of dexamethasone administration is crucial. If used, it should be administered before or with the first dose of antibacterial therapy. This is to counteract the initial inflammatory burst consequent to antibiotic-mediated bacterial killing. A more intense inflammatory reaction has been documented following the massive bacterial killing induced by antibiotics.

In a meta-analysis, dexamethasone had no effect in any of the prespecified subgroups, including specific causative organisms, predexamethasone antibiotic treatment, HIV status, or age. The meta-analysis was also unable to show a significant reduction in death or neurologic disability.^[26]

In developing countries, the use of oral glycerol (rather than dexamethasone) has been studied as adjunctive therapy in the treatment of bacterial meningitis in children. In limited studies, it appears to reduce the incidence of neurologic sequelae with few side effects.^[27]

Guidelines from the Infectious Disease Society of America (IDSA) recommend adjunctive dexamethasone in adults and children with pneumococcal meningitis or tuberculous meningitis and in children with H influenzae type b meningitis. The IDSA found insufficient data to make a recommendation on the use of adjunctive dexamethasone in neonates with bacterial meningitis.^[21] The American Academy of Pediatrics advises that the available data on adjunctive dexamethasone are not sufficient to make a recommendation for children.^[28]

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