Review: Adjuvant corticosteroid therapy reduces death, hearing loss, and neurologic sequelae in bacterial meningitisPDF
ACP J Club. 2004 Mar-Apr;140:34. doi:10.7326/ACPJC-2004-140-2-034
Clinical Impact Ratings
van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev. 2003;(3):CD004305. [PubMed ID: 12918010]
In children and adults with acute bacterial meningitis (ABM), is adjuvant corticosteroid therapy more effective than placebo for reducing mortality, hearing loss, and neurologic sequelae?
Studies were identified by searching the Cochrane Central Register of Controlled Trials (2003), MEDLINE (1966 to January 2003), EMBASE/Excerpta Medica (1974 to April 2002), and HEALTHLINE (1988 to April 2002); reviewing current trials published before April 2002; searching the reference lists of published studies; hand-searching abstracts of congresses; and contacting researchers and experts in the field.
Study selection and assignment
Studies in any language were selected if they were randomized controlled trials that compared any type of corticosteroid therapy adjuvant to antibiotics (e.g., third-generation cephalosporins) with placebo in patients with ABM and recorded case fatality rates. 2 reviewers independently assessed the quality of studies using the Jadad scale.
Mortality, severe hearing loss (bilateral hearing loss > 60 dB or requiring bilateral hearing aids), and short-term (discharge to 6 wk) or long-term (6 to 12 mo after discharge) neurologic sequelae.
18 studies (1853 patients) met the selection criteria. Overall, fewer patients who received corticosteroids died than did those who received placebo (Table); groups did not differ for mortality in 14 studies with children only (relative risk [RR] 0.95, 95% CI 0.65 to 1.37). Fewer patients in the corticosteroid group had severe hearing loss than did those in the placebo group (Table). Children with ABM from pathogens other than Hemophilus influenzae who received corticosteroids also had a reduced risk for hearing loss (RR 0.42, CI 0.20 to 0.89). Although the groups did not differ in 7 studies for short-term neurologic sequelae (RR 0.72, CI 0.48 to 1.06), the corticosteroid group had a reduction in risk for long-term neurologic sequelae (Table). Groups did not differ for adverse events.
In children and adults with acute bacterial meningitis, adjuvant corticosteroid therapy reduces mortality, hearing loss, and long-term neurologic sequelae.
Source of funding: No external funding.
For correspondence: Dr. D. van de Beek, University of Amsterdam, The Netherlands. E-mail firstname.lastname@example.org.
Table. Corticosteroids vs placebo for acute bacterial meningitis at up to 12 months*
|Outcomes||Patients||Number of studies||Weighted event rates|
|Corticosteroids||Placebo||RRR (95% CI)||NNT (CI)|
|Mortality||All||18||8.6%||11.6%||24% (3 to 41)||34 (20 to ∞)|
|Adults||3||8%||21%||62% (22 to 82)||8 (5 to 25)|
|Severe hearing loss||All||13||2.4%||7.4%||63% (38 to 78)||20 (15 to 50)|
|Children||12||2.8%||9.8%||69% (46 to 82)||15 (10 to 25)|
|Long-term neurologic sequelae||All||10||6%||9%||55% (0 to 55)||34 (17 to ∞)|
*Abbreviations defined in Glossary; weighted events, RRR, NNT, and CI calculated from data in article using a fixed-effects model.
ABM remains one of the most catastrophic of infectious diseases. Victory against ABM requires the same strategies used against other life-threatening infectious diseases: prevention (with vaccination and effective public health measures), killing of invading organisms, and suppressing the host's deleterious immune response. Although recent vaccine developments against ABM have shifted the proportion of infections to adults in developed countries, ABM continues to threaten both children and adults in developing countries.
Failed treatment of ABM is rarely a bug-and-drug problem despite recent concerns about drug-resistant pneumococci and meningococci. The fact that a host's immune response causes the bulk of neurologic morbidity in ABM (which can be attenuated by adjunctive corticosteroids before administering antibiotics) has been supported by extensive animal research. Vancomycin does not cross the rabbit blood–brain barrier effectively when meningeal inflammation is reduced, raising the concern that corticosteroids might reduce the effectiveness of vancomycin in humans. However, in children with ABM caused by cephalosporin-resistant pneumococci, cerebrospinal fluid penetration of vancomycin seems unaffected by adjunctive use of corticosteroids (1).
van de Beek and colleagues should be commended on a sound review of the effect of corticosteroids on ABM in children and adults. A similar meta-analysis done with fewer eligible studies reached similar conclusions for childhood ABM and remained cautious regarding the use of corticosteroids in adults with ABM (2). More important, a recent randomized controlled trial by de Gans and van de Beek showed that corticosteroids were beneficial in ABM, especially in pneumococcal meningitis (which has the gravest prognosis) (3). Corticosteroids should be given as early as possible in all cases of ABM, using the published dose of dexamethasone, 10 mg every 6 hours in adults, or 0.4 to 0.6 mg/kg per d divided in 4 daily doses for children for 4 days. Ideally, dexamethasone should be administered before the antibiotics.
Andrew M. Morris, MD, MSc, FRCPC
Hamilton, Ontario, Canada
1. Klugman KP, Friedland IR, Bradley JS. Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis. Antimicrob Agents Chemother. 1995;39:1988-92. [PubMed ID: 8540704]
2. McIntyre PB, Berkey CS, King SM, et al. Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988. JAMA. 1997;278:925-31. [PubMed ID: 9302246]
3. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347:1549-56. [PubMed ID: 12432041]