The Role for Steroids in Childhood Meningitis
ABSTRACT & COMMENTARY
Source: McIntyre PB, et al. Dexamethasone as adjunctive therapy in bacterial meningitis: A meta-analysis of randomized clinical trials since 1988. JAMA 1997;278:925-931.
In the last decade, the pediatric and infectious disease literature has been bombarded with small- to medium sized studies examining the role of dexamethasone in pediatric meningitis. Most of the studies suffered from small sample sizes and variable dosing and timing of dexamethasone, making head-to-head comparisons difficult. To further complicate the steroid question, release and widespread use of the Haemophilus influenzae type b (Hib) vaccine led to a marked decline (> 80%) in invasive Hib disease.1 To try to settle the question, McIntyre and colleagues performed a meta-analysis examining the relationship between steroids in meningitis and patient outcome, looking only at studies published between 1988 and 1996.
McIntyre et al sought to answer four questions with regard to dexamethasone and pediatric meningitis: the value of steroids in non-Hib meningitis; the timing of steroid dose relative to antibiotic therapy; the effect of dexamethasone on non-hearing-loss neurologic deficits; and the frequency of adverse events related to dexamethasone therapy. Eleven randomized, controlled trials met entry criteria for the meta-analysis and included more than 900 children, most in the 12-24-month age group.
The incidence of severe hearing loss in the control group (antibiotic alone) was as follows: 11.6% for Hib meningitis; 19.6% for pneumococcal meningitis; and 0% for meningococcal meningitis. Dexamethasone was significantly protective against severe audiologic deficit in children with Hib meningitis (odds ratio = 0.31). For Streptococcus pneumoniae meningitis, the protective effect of steroids was seen only when dexamethasone was administered before or with the first dose of antibiotic (odds ratio 0.09 for early steroid administration vs 1.24 with later dosing). When examining the effects of steroids on other neurologic deficits or less severe hearing loss, the combined odds ratio favored dexamethasone with borderline statistical significance. The duration of steroid therapy was difficult to compare as regimens varied from two to four days, but the incidence of gastrointestinal bleeding increased with the four-day regimen without clear benefit in neurologic outcome.
COMMENT BY KATHERINE L. HEILPERN, MD
In summary, this is the first study to critically realize the difference in the frequency of severe hearing loss between Hib, pneumococcal, and meningococcal meningitis in patients receiving antibiotics alone. The role of steroids in Hib meningitis is clearly protective regardless of timing of the steroid dose, while patients with pneumococcal meningitis gain benefit only with administration of dexamethasone prior to, or in conjunction with, the first antibiotic dose. While statistically marginal, the study supports a protective role for dexamethasone against other neurologic sequelae in all three types of meningitis.
Needless to say, we cannot guess the bacterial organism when we stare at a critically ill child. In my practice, if I have a moderate-to-high suspicion that a child has meningitis, I give a dose of dexamethasone 0.15 mg/kg with my first dose of antibiotics. Increasing S. pneumoniae resistance to third-generation cephalosporins has created concern with regard to interactions between vancomycin and dexamethasone. Animal studies suggest that dexamethasone may decrease vancomycin penetration into the CSF, but a recent study in children did not bear that out.2
References
1. Adams WG, et al. Decline in childhood Haemophilus influenzae type b disease in the Hib vaccine era. JAMA 1993;269;221-248.
2. Klugman KP, et al. Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in CSF of children with acute bacterial meningitis. Antimicrob Agents Chemother 1995;39:1988-1992.
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