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• W57796164 abstract "I appreciate the opportunity to comment once more on the issue of corticosteroid therapy in children with meningitis and to respond to the criticism of my recent commentary on the subject (1). I am heartened that my comments have generated some debate.Sebire and Cyr (1) were surprised that I doubted the benefit of corticosteroids for pneumococcal meningitis in children. Any opinions that I expressed were my own and I take complete responsibility for them. However, I should note that I am not alone in my opinion or preferred action. A recent survey of Canadian paediatric infectious diseases specialists found that only a minority (34%) would recommend corticosteroid therapy for suspected pneumococcal meningitis (2). More telling, a review of cases of pneumococcal meningitis from six tertiary care paediatric centres across Canada in the 1990s found that empirical corticosteroid use declined sharply over the decade, from 73% of cases in 1991 to 1993, to 21% of cases in 1994 to 1996, to just 5% of cases in 1997 to 1999 (3). Of course, it was during the 1990s that Haemophilus influenzae type b meningitis (for which the value of corticosteroids is more clear cut) essentially disappeared in Canada, thanks to universal immunization (4,5).Sebire and Cyr referred to the uniformity of specialist opinion to use corticosteroids for meningitis. However, it should be noted that two of the three authors they refer to only recommended corticosteroids for adults with meningitis (6), and the third author made recommendations in a review article under the heading of “Personal view” (7).Is my opinion, as well as the beliefs and practices of other Canadian physicians, refuted by the recent meta-analysis of van de Beek et al (5)? Sebire and Cyr stated that this study “could end this old controversy” about corticosteroids for pneumococcal meningitis in children (1). However, I do not think that van de Beek’s study provides any more definitive or helpful results than were previously known for children. Thus, I stand by original assertions that the clinical course of meningitis in children and adults is very different, and that corticosteroids are unnecessary for the treatment of suspected bacterial meningitis in Canadian children, unless H influenzae type b is suspected.A brief consideration of the similarities and differences between van de Beek et al’s meta-analysis (5) and the earlier, related meta-analysis by McIntyre et al (8) that I previously referred to (McIntyre is an author in both studies), reveals the old adage that “the devil is in the detail”. Both studies stated that only placebo-controlled clinical trials were included and that trials without a clear description of randomization were excluded. The study by van de Beek et al (5) included four clinical trials published before 1988 and three clinical trials published since 1996 that were not included in the meta-analysis by McIntyre et al (8).In addition, van de Beek et al (5) referred, in an erratum, to very recent data from the landmark clinical trial by de Gans et al (9) of corticosteroid use for pneumococcal meningitis in adults (which showed a large benefit of preventing death). van de Beek et al (5) rightly used the data from that study to strengthen their conclusion about the benefits of corticosteroids to prevent death in adults with bacterial meningitis.In contrast, van de Beek et al (5) dismissed as irrelevant the very recent clinical trial by Molyneux et al (10) of corti-costeroid use for meningitis in children in Malawi (which found no benefit). The dismissal of the Malawian study is inconsistent with their stated inclusion and exclusion criteria because that recent clinical trial was placebo-controlled and randomization was clearly described. The dismissal of the patient population as “not representative” for “industrialized countries” is inconsistent given that studies from Costa Rica, Egypt, Mozambique, Pakistan and Turkey were included (5). The Malawian clinical trial was the largest ever placebo-controlled trial for meningitis treatment (n=598). It would have increased the sample of 1480 children from all of the other trials by 40% and would have reduced any apparent benefit of corticosteroids found in the other trials.What were the main findings of van de Beek et al (5)? First, they found that corticosteroids reduced mortality from all forms of meningitis, including pneumococcal meningitis, in adults, but not in children. As I discussed in my previous commentary, this key difference is not surprising because of the observation that the much higher mortality rate in adults than in children (eg, 34% in the placebo arm of the study by de Gans et al [9] versus 7% in Canadian children in the 1990s [11]) is related to the higher proportion of adult cases complicated by severe systemic disease. van de Beek and de Gans (12) explained this difference by noting that corti-costeroids were by far most effective for preventing deaths in those with severe systemic disease (septic shock, multiorgan failure, respiratory failure or cardiac ischemia), but they did not prevent deaths due to neurological causes (12).Another finding was that corticosteroids prevented severe hearing loss in children with all forms of meningitis (61% of combined cases were H influenzae type b), but not for pneumococcal meningitis considered separately (5). Of note, when all cases except those caused by H influenzae type b were combined, a statistically significant benefit from corticosteroids was found. However, inclusion of the large Malawian study would have rendered this finding insignificant.As Sebire and Cyr clearly highlight, bacterial meningitis leads to a profound inflammatory response in the central nervous system. The appeal to consider anti-inflammatory treatment is obvious. There is no doubt that corticosteroids are beneficial for the treatment of inflammation in some infectious diseases (eg, croup) (13–15). For others, there is either no demonstrated benefit (eg, acute pharyngitis) (16) or the potential for harm, at least in the wrong dose (eg, septic shock) (17,18). For many other conditions (eg, tuberculosis meningitis), the evidence for a benefit or harm from corticosteroids is limited, yet strong opinions about their use have been expressed (19).Will we ever know more about the use of corticosteroids for children with pneumococcal meningitis and other forms of bacterial meningitis? For the foreseeable future, it seems unlikely. In developed countries, effective vaccines have already (for H influenzae type b) or will soon (for pneumococcus and Neisseria meningitidis) dramatically reduce the incidence of bacterial meningitis. This positive development will likely make further large-scale clinical trials unfeasible, as well as less important. In developing countries, bacterial meningitis unfortunately remains common, and the implementation of new vaccines will likely take many years. However, the results of the Molyneux et al (10) study from Malawi provide strong, up-to-date evidence against the use of corticosteroids in developing countries. It seems unlikely that the prodigious effort to conduct this study will be replicated elsewhere.Thus, individual Canadian physicians must continue to use imperfect data to inform their decision about whether to use empirical corticosteroid therapy in cases of suspected bacterial meningitis." @default.
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• W57796164 date "2006-01-01" @default.
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• W57796164 title "Response to ‘Benefits of glucocorticoids in the treatment of bacterial meningitis in children: End of the controversy?’" @default.
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