Diederik van de Beek, MD, PhD; Jan de Gans, PhD
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van de Beek D., de Gans J.; Dexamethasone and Pneumococcal Meningitis. Ann Intern Med. 2004;141:327. doi: 10.7326/0003-4819-141-4-200408170-00028
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Published: Ann Intern Med. 2004;141(4):327.
TO THE EDITOR:
Background: Dexamethasone reduces mortality rates in adults with pneumococcal meningitis (1).
Objective: We wanted to determine whether the beneficial effect of dexamethasone on mortality rates in adults with pneumococcal meningitis is attributable to beneficial effects on neurologic or systemic complications.
Methods and Findings: We did a post hoc analysis of the European Dexamethasone in Adulthood Bacterial Meningitis Study (1). We included patients who had pneumococcal meningitis proven by cerebrospinal fluid culture. Deaths within 14 days after admission were categorized; we chose a survival point of 14 days because deaths within this period were probably directly related to meningitis (2).
Andre C. Kalil
University of Nebraska Medical Center
August 20, 2004
The Use of Dexamethasone in Bacterial Meningitis
Drs. van de Beek and de Gans (1) found that ""¦the beneficial effect of dexamethasone on mortality rates in patients with pneumococcal meningitis is attributable to a beneficial effect on systemic complications (i.e. septic shock, respiratory failure, multi-organ dysfunction and cardiac ischemia)". This clinical observation is interesting, particularly in lieu of the growing data on the effects of steroids in septic shock just published in this journal (2), despite the use of different drug regimens (4).
However, both this new clinical observation (1) and the original editorial by Tunkel and Scheld (3) did not address the remaining 64% of the trial population (4) which consisted of patients with "˜N. meningitidis' (n = 97), "˜other bacteria' (n = 29) and "˜negative culture' (n = 67). The statements "Dexamethasone reduces mortality rates in adults with pneumococcal meningitis" (1) and "if the meningitis is found not to be caused by S. pneumoniae, dexamethasone therapy should be discontinued" (3) do not accurately reflect the trial results (4).
The overall results (4) were based on a total of 301 patients with multiple causes of bacterial meningitis, and not on the S. pneumoniae subgroup alone. Following CONSORT guidelines, the Breslow-Day test for interaction yields p-values of 0.20 for "˜death' and 0.37 for "˜unfavorable outcome', indicating no significant effect of S. pneumoniae status on the magnitude of the treatment effect. Thus, the lack of significant interaction does not support the conclusion that the subgroups are heterogeneous nor the recommendation for dexamethasone in pneumococcal meningitis only.
Alternatively, the benefits of steroids in bacterial meningitis may depend on the baseline risk of death, as seen in sepsis trials (5). The larger effect seen in the pneumococcal group, which had higher control mortality (34%), compared to the one seen in the meningococcal group (2%) supports this concept. It would be of interest to analyze the dexamethasone effect based on whether or not septic shock was present at study entry.
Noteworthy, the number of deaths by pneumococcal meningitis in this post hoc study was 18, whereas in the original trial it was 25 (4). This discrepancy appears to be due to the use of different end points. While I understand the choice of a 14-day survival end point, the 8-week end point used in the original trial should also be reported in this subgroup study. In addition, it would be more representative of the original trial and informative to the clinician if the same post hoc analysis was performed on all 301 patients (4).
1. van de Beek D, de Gans J. Dexamethasone and pneumococcal meningitis. Ann Intern Med 2004;141:321.
2. Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C. Meta- analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 2004;141:47-56.
3. Tunkel AR, Scheld WM. Corticosteroids for everyone with meningitis? N Engl J Med 2002;347:1613-14.
4. de Gans J, van de Beek D. Dexamethasone in adults with bactereial meningitis. N Engl J Med 2002;347:1549-56.
5. Eichacker PQ, Parent C, Kalil A, Esposito C, Cui X, Banks SM, et al. Risk and efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 2002;166:1156- 7.
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