Steroids for Bacterial Meningitis: Long-term Follow-up

Abstract & Commentary

By Joseph Safdieh, MD, Assistant Professor of Neurology, Weill Cornell Medical College. Dr. Safdieh reports no financial relationships relevant to this field of study.

Synopsis: Use of dexamethasone in community-acquired bacterial meningitis is associated with long-term survival in treated patients.

Source: Fritz D, et al. Dexamethasone and long-term survival in bacterial meningitis. Neurology 2012;79:2177-2179.

Bacterial meningitis is a serious, often life-threatening, condition. Patients generally present with acute onset of fever, headache, and nuchal rigidity, and often have associated photophobia, nausea, and altered mental status. The diagnosis can be made quickly with lumbar puncture and patients clearly benefit from early initiation of appropriate intravenous antimicrobial therapy. Because many of the complications arise due to the overwhelming systemic immune response in meningitis, most experts recommend early administration of steroids in addition to antibiotics.

In 2002, an important paper demonstrated the overall benefit of early administration of intravenous dexamethasone in European adults with community-acquired bacterial meningitis.1 In that study, the risk of unfavorable outcomes was reduced from 25% to 15% in the patients randomized to dexamethasone as compared to placebo. More specifically, at 8 weeks after randomization, 11 of 157 (7%) patients died in the dexamethasone group and 21 of 144 (15%) patients died in the placebo group (P = 0.04).

In the current study, the authors presented the long-term mortality data on this original cohort of patients to determine whether this mortality benefit was durable. This analysis was especially important in light of another recent study2 demonstrating that in meningitis due to tuberculosis, the benefit of steroids was only an early effect, and patients who received steroids actually “caught up” to the placebo group in terms of mortality over time.

The authors used the national database of the Netherlands to track mortality of the original cohort of patients. Of these patients, 93% could be followed. By 2011 (median follow-up of 13 years after enrollment), 31 of 144 (22%) patients in the dexamethasone group had died and 44 of 134 (33%) patients in the placebo group had died. Over the follow-up period after the primary outcome measure at 8 weeks, 20 additional patients in the dexamethasone group and 23 additional patients in the placebo group had died. After the initial 8 weeks of enrollment, the slope of the survival curves did not change between the groups. The beneficial effect in long-term survival was most apparent in the group of patients with pneumococcal meningitis.

Commentary

This study demonstrated that the initial benefit of steroids on mortality of patients with bacterial meningitis continues to be apparent over the subsequent years. There is no additional benefit to steroids after the 8-week period, but the steroid group maintains a durable, long-term survival advantage over the placebo group. This is the first study to demonstrate this degree of long-term mortality benefit and should serve to reassure physicians that there is no long-term delayed detrimental effect on mortality when treating bacterial meningitis patients in the acute setting with dexamethasone. In fact, the early benefit endures for many years to come.

References

1. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549-1556.

2. Torok ME, et al. Dexamethasone and long-term outcome of tuberculosis meningitis in Vietnamese adults and adolescents. PLoS One 2011;6:e27821. doi: 10.1371/journal.pone.0027821.