Abstract
In experimental meningitis, adjunctive treatment with steroids reduces cerebrospinal fluid inflammation and thereby improves neurological outcome. On the basis of these findings, several clinical trials have assessed treatment with adjunctive steroids in bacterial meningitis, with conflicting results. Recently, the results of the European Dexamethasone Study showed a beneficial effect of adjunctive dexamethasone in adults with bacterial meningitis. In that study, the effect of dexamethasone on outcome was most striking in patients with pneumococcal meningitis. The aim of the present study was to further evaluate the effect of dexamethasone in adults with pneumococcal meningitis by performing a post hoc analysis of the European Dexamethasone Study. In a multivariate analysis, tachycardia (p=0.02), advanced age (p=0.03), low score on the Glasgow Coma Scale (p=0.03), positive blood culture (p=0.04), and absence of dexamethasone therapy (p=0.05) were independent predictors for death. Patients who were treated with adjunctive dexamethasone were less likely to develop both systemic and neurological complications during hospitalisation, compared with patients who received placebo. In conclusion, independent risk factors for death in pneumococcal meningitis are tachycardia, advanced age, low level of consciousness, bacteraemia, and absence of dexamethasone therapy. Treatment with adjunctive dexamethasone in adults with pneumococcal meningitis reduces both systemic and neurological complications.
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References
Koedel U, Scheld WM, Pfister HW (2002) Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis 2:721–736
Scheld WM, Dacey RG, Winn HR, Welsh JE, Jane JA, Sande MA (1980) Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone. J Clin Invest 66:243–253
Tauber MG, Khayam-Bashi H, Sande MA (1985) Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis. J Infect Dis 151:528–534
van de Beek D, de Gans J, McIntyre P, Prasad K (2003) Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev, The Cochrane Library, record no. CD004305
McIntyre PB, Berkey CS, King SM et al (1997) Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988. JAMA 278:925–931
Schuchat A, Robinson K, Wenger JD et al (1997) Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med 337:970–976
Girgis NI, Farid Z, Mikhail IA, Farrag I, Sultan Y, Kilpatrick ME (1989) Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J 8:848–851
de Gans J, van de Beek D (2002) Dexamethasone in adults with bacterial meningitis. N Engl J Med 347:1549–1556
van de Beek D, de Gans J, McIntyre P, Prasad K (2004) Steroids in adults with acute bacterial meningitis: a systematic review. Lancet Infect Dis 4:139–143
van de Beek D, de Gans J (2004) Dexamethasone and pneumococcal meningitis. Ann Intern Med 141:327
Tunkel AR, Hartman BJ, Kaplan SL et al (2004) Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39:1267–1284
Jennet B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1:480–484
Hosmer DW, Lemeshow S (1989) Applied logistic regression. Wiley, New York, pp 140–145
Kastenbauer S, Pfister HW (2003) Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases. Brain 126:1015–1025
Tunkel AR (2001) Bacterial meningitis. Lippincott Williams & Wilkins, Philadelphia, pp 179–190
Mustafa MM, Ramilo O, Mertsola J et al (1989) Modulation of inflammation and cachectin activity in relation to treatment of experimental Haemophilus influenzae type b meningitis. J Infect Dis 160:818–825
van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M (2004) Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 351:1849–1859
Auburtin M, Porcher R, Bruneel F et al (2002) Pneumococcal meningitis in the intensive care unit: prognostic factors of clinical outcome in a series of 80 cases. Am J Respir Crit Care Med 165:713–717
Babyak MA (2004) What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models. Psychosom Med 66:411–421
Annane D, Sebille V, Charpentier C et al (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871
Tunkel AR, Scheld WM (2002) Corticosteroids for everyone with meningitis? N Engl J Med 347:1613–1615
Cooper MS, Stewart PM (2003) Corticosteroid insufficiency in acutely ill patients. N Engl J Med 348:727–734
Lutsar I, Friedland IR, Jafri HS et al (2003) Factors influencing the anti-inflammatory effect of dexamethasone therapy in experimental pneumococcal meningitis. J Antimicrob Chemother 52:651–655
Whitney CG, Farley MM, Hadler J et al (2000) Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med 343:1917–1924
Klugman KP, Friedland IR, Bradley JS (1995) Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis. J Antimicrob Agents Chemother 39:1988–1992
Viladrich PF, Gudiol F, Linares J et al (1991) Evaluation of vancomycin for therapy of adult pneumococcal meningitis. Antimicrob Agents Chemother 35:2467–2472
van de Beek D, de Gans J, Tunkel AR, Wijdicks EF (2006) Adults with community-acquired bacterial meningitis. N Engl J Med 354:44–53
Leib SL, Heimgartner C, Bifrare YD, Loeffler JM, Tauber MG (2003) Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats. Pediatr Res 54:353–357
van de Beek D, Schmand B, de Gans J et al (2002) Cognitive impairment in adults with good recovery after bacterial meningitis. J Infect Dis 186:1047–1052
Pomar V, Martinez S, Paredes R, Domingo P (2004) Advances in adjuvant therapy against acute bacterial meningitis. Curr Drug Targets Infect Disord 4:303–309
Acknowledgement
The European Dexamethasone in Adulthood Bacterial Meningitis Study was sponsored by a research grant of NV Organon, the Netherlands (USD 30,000). The study was designed, conducted, and analysed independently of the sponsor. There is no potential conflict of interest for any of the authors involved.
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Weisfelt, M., van de Beek, D. & de Gans, J. Dexamethasone treatment in adults with pneumococcal meningitis: risk factors for death. Eur J Clin Microbiol Infect Dis 25, 73–78 (2006). https://doi.org/10.1007/s10096-006-0089-z
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DOI: https://doi.org/10.1007/s10096-006-0089-z