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Slide 19 The duration of antimicrobial therapy is based on the causative agent, the clinical response and the development of complications. The recommendations for uncomplicated meningitis is listed in the table. It has been the practice to treat meningococcal for 7-10 days and other pathogens with longer regimens. Clinical trials have shown that meningococcal meningitis may be effective treated in seven days, and in majority of patients were cured in 4-5 days. For non-meningococcal meningitis, primarily H. influenzae, therapy with seven days of ceftriaxone was as effective as ten days of therapy. Comparative studies for duration of treatment of S.pneumoniae, Group B streptococcus, L. monocytogenes and enteric gram negative bacilli are lacking.

Slide 20 Although the host's inflammatory response is critical to clear bacterial pathogens, it appears that most CNS injury is the result of inappropriate intensity and timing of beneficial response. Among the host factors which lead to damage in meningitis, the proinflammatory cytokines such as TNF, and IL1. These cytokines promote a destructive leukocyte-cerebral capillary endothelial cell interaction, platelet mediated thrombosis and cytotoxic, interstitial and vasogenic cerebral edema. The beneficial effect dexamethasone stems from its action of inhibiting the synthesis of TNF and IL1 at the level of the mRNA.

Slide 21 In a meta-analysis of 11 randomized clinical trials with mostly H. influenzae meningitis, it was shown to reduce the incidence of severe hearing loss, but it did not significantly reduce the case fatality rate. Since 1994, the Infectious Disease Committee of the American Academy of Pediatrics has recommended the routine use of dexamethasone for meningitis in children over 2 months old caused by H. influenzae, and also be considered for use in meningitis caused by other etiologic agents.

Slide 22 Review of the few studies of adjunctive steroid therapy from developing countries produced different results from those in developed countries. In Islamabad, the dexamethasone group had an increased risk of sequelae (especially hearing loss), and even higher mortality. Another study in Pakistan showed higher mortality in the dexamethasone group and hardly any differences in rates of neurologic sequelae and hearing impairment among the dexamethasone group and the placebo group. This results could be due to the difference in conditions from developed countries such as late presentations of patients, use of antibiotics prior to hospital presentation and CSF results wherein no bacteria was isolated. In the 1997 WHO Workshop on the Treatment of Bacterial Meningitis in Developing Countries, the conclusion was that the routine use of dexamethasone as adjuvant therapy in bacterial meningitis was not recommended. *Qazi, et al. Arch Dis Childhood 1996; 75: 482-488

Slide 23 The Task Force also reviewed these researches, and since the Philippines is also a developing country with similar conditions as those wherein the data was collected, it was also recommended that dexamethasone shall not be used routinely in all patients with bacterial meningitis.

Slide 24 Dexamethasone may be considered to be used if facilities are available to reliably diagnose if the child has H. influezae meningitis immediately. It may also be used in patients with markedly increased intracranial pressure. It is recommended that dexamethasone be given for 2 days only since studies have found this to be as effective as four days but with reduced complications. Dexamethasone should also be given with an H2 blocker in order to reduce the incidence of gastrointestinal bleeding.

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