CORTICOSTEROIDS IN BACTERIAL MENINGITIS: WHAT’S NEW, WHAT’S TRUE?

In their review about adjunctive steroid (AS) treatment in acute bacterial meningitis (ABM), Spapen et al propose that, awaiting a new worldwide trial, AS should be abandoned in this setting (1). However, we have some concerns about their arguments. Firstly, the authors recognize that treatment with dexamethasone signifi cantly reduced the risks of both unfavourable outcome and death in a European prospective randomized trial on 301 adult patients published in 2002 (2), but they outline that these data were not confi rmed in more recent studies (3-6). The truth is that the two leaders of the European study, de Gans and van de Beek, confi rmed their initial results in two meta-analysis (including a Cochrane review with data from 20 randomized controlled trials involving 2750 patients and published in 2007), showing an overall mortality benefi t and a reduction in neurological sequelae in patients treated with AS (7, 8). The same year , three large randomized controlled studies led to potentially diff erent conclusions [respectively including 329 children from Latin America (3), 435 adult Vietnamese patients (4), and 465 adults from Malawi – 90% of whom were HIV positive – (5)]. Consequently, de Gans and van de Beek performed a new meta-analysis (9) including the three aforementioned studies (3-5), another trial involving 598 children from Malawi (6) and the European study (2). The conclusion of this meta-analysis was that AS does not signifi cantly reduce death or neurological disability despite the fact that dexamethasone reduces hearing loss among survivors (24.1% vs 29.5%; 0·77, 0.60-0.99, p = 0.04). In view of the obvious bias of this meta-analysis towards patients from developing countries, particularly the two studies from Malawi where the mortality rates were threeto fi ve-fold higher than in the studies from Europe, South America and Vietnam, the authors recently published the largest and more complete Cochrane analysis to date, including 24 studies and involving 4041 participants (10). They concluded that for participants of any age, corticosteroids signifi cantly reduce hearing loss and neurological sequelae, but do not reduce overall mortality despite a trend towards lower mortality in adults (RR 0.74, 95% CI 0.53 to 1.05, p = 0.09). However, subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae meningitis (RR 0.84, 95% CI 0.72 to 0.98). These data support the use of corticosteroids in patients with ABM in high-income countries but without benefi cial eff ect in low-income countries and are in accordance with the two meta-analyses on the use of AS in adults published in 2009: AS treatment signifi cantly reduces mortality in highincome countries (11) and in all adults (12) after excluding the trial involving adults from Malawi (5). Secondly, Spapen et al. state that the decreased mortality reported in the initial study published in 2002 could be explained by a reduction in systemic (septic shock and acute lung injury) rather than neurological complications, following a post-hoc analysis of the European study in patients with pneumococcal meningitis (13). This explanation remains purely speculative since the use of corticosteroids in septic shock remains debated as stated in a recent review article: “Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefi t on mortality” (14). Moreover, recent guidelines for management of severe sepsis and septic shock suggest that patients with septic shock should not receive dexamethasone if hydrocortisone is available (15). Thirdly, Spapen et al. outline that steroids can reduce the penetration of antibiotics (particulary vancomycin) into the cerebrospinal fluid. Actually, de Gans et al had already expressed concerns in this regard and noticed that therapeutic failures had been described in adults treated with standard doses of vancomycin and adjunctive steroids advising that “patients with pneumococcal meningitis who are treated with vancomycin and steroids should be carefully monitored throughout therapy “ (2, 7). Accordingly, guidelines published by the Infectious Disease Society of America in 2004 (16) support the use of AS in ABM but specify the limitations of the use of vancomycin in this setting. Furthermore, what is true in the US in terms of incidence of strains highly resistant to penicillin and cephalosporin is not obviously true worldwide in general