AMSTERDAM—Antimicrobial therapy can clear infection from the cerebrospinal fluid (CSF) of acute bacterial meningitis patients within 48 hours. Yet, antibiotic-treated adults with meningitis still suffer high mortality or persistent neurologic sequelae. New work demonstrates that brief adjuvant corticosteroid therapy significantly improves outcomes and halves the risk of death in adult patients with acute bacterial meningitis.[1]

“Treatment with dexamethasone was associated with a reduction in unfavorable outcomes [and] in mortality—in all patients, but especially in those patients with pneumococcal meningitis,” said Jan de Gans, PhD, a neurologist at the Academic Medical Center of the University of Amsterdam and primary author of the study. “When a patient has meningitis, there is an extreme inflammatory response in the CSF,” he pointed out. Animal models of meningitis show elevated levels of inflammatory cytokines; antibiotic therapy can actually exacerbate inflammation by enhancing bacterial lysis.

“The thought is that the inflammatory cytokine cascade … does more harm than good,” explained coauthor Diederik van de Beek, MD, a neurology resident at the center. However, he noted, “when you treat these animals with dexamethasone, the inflammatory response decreases, and this is associated with a better outcome.” Protection conferred by adjunctive dexamethasone therapy in pediatric meningitis thus prompted a prospective, randomized, controlled trial in adults.

A total of 301 adult patients with bacterial meningitis were given either dexamethasone (10 mg; n = 157) or placebo (n = 144) at the start of antimicrobial courses; the dose was repeated every six hours for the next four days. Both groups received similar antibiotic therapy; 77% of the patients received amoxicillin or penicillin, 8% were given a third-generation cephalosporin, and another 8% received drugs from both classes.

DEXAMETHASONE IMPROVES OUTCOME

Eight weeks after enrollment, unfavorable outcomes (death or severe or moderate disability) had developed in 36 (25%) placebo recipients—a proportion significantly higher than the 23 patients (15%) in the dexamethasone group who suffered such outcomes; the relative risk (RR) associated with dexamethasone use was 0.59. Further, among those infected with Streptococcus pneumoniae, dexamethasone halved the rate of unfavorable outcomes (from 52% to 26%). Dexamethasone also drastically reduced mortality among all patients (from 15% to 7%; RR, 0.48) and among pneumococcal patients (from 34% to 14%; RR, 0.41).

“Occurrence of gastrointestinal tract bleeding was not higher, so dexamethasone is a relatively safe medication,” Dr. van de Beek observed. “We give it at a relatively high dosage, but only for four days, so it’s unlikely that you’d have serious side effects.”

Dexamethasone clearly improved outcome in patients with pneumococcal meningitis, but not in those with nonpneumococcal infection. This apparent difference might stem partly from the paucity of subjects with nonpneumococcal meningitis, but it may also reflect the higher inflammatory cytokine levels seen with pneumococcal infection. Although dexamethasone’s utility in nonpneumococcal meningitis remains unclear, Dr. van de Beek emphasized, “you ethically can’t perform another study, because it’s such a huge [overall] effect, especially on mortality.” Therefore, concluded Dr. de Gans, “Our advice is to give it to all adults with bacterial meningitis.”

—Mimi Zucker, PhD