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Drug Insight: adjunctive therapies in adults with bacterial meningitis

Nature Clinical Practice Neurology volume 2, pages 504–516 (2006)Cite this article

Abstract

Despite the availability of effective antibiotics, mortality and morbidity rates associated with bacterial meningitis are high. Studies in animals have shown that bacterial lysis, induced by treatment with antibiotics, leads to inflammation in the subarachnoid space, which might contribute to an unfavorable outcome. The management of adults with bacterial meningitis can be complex, and common complications include meningoencephalitis, systemic compromise, stroke and raised intracranial pressure. Various adjunctive therapies have been described to improve outcome in such patients, including anti-inflammatory agents, anticoagulant therapies, and strategies to reduce intracranial pressure. Although a recent randomized trial provided evidence in favor of dexamethasone treatment, few randomized clinical studies are available for other adjunctive therapies in adults with bacterial meningitis. This review briefly summarizes the pathogenesis and pathophysiology of bacterial meningitis, and focuses on the evidence for and against use of the available adjunctive therapies in clinical practice.

Key Points

  • Common complications of bacterial meningitis include meningoencephalitis, systemic compromise, stroke and raised intracranial pressure

  • Potential adjunctive therapies to manage these complications include anti-inflammatory agents, anticoagulant therapies, and strategies to reduce intracranial pressure

  • Dexamethasone is the only currently accepted adjunctive therapy for the treatment of patients with bacterial meningitis; no other adjunctive therapy has proven clinical efficacy

  • For the future, drugs that increase fibrinolysis, such as nimodipine, should be explored in experimental meningitis models, and clinical trials should be performed to evaluate moderate hypothermia, intensive insulin therapy and glycerol in patients with bacterial meningitis

  • Advances in experimental meningitis are promising, and, among the new therapies arising from these studies, N-acetylcysteine seems to be closest to a clinical application

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Figure 1: Multiple complications in a patient with pneumococcal meningitis.
Figure 2: Simplified diagram of pathophysiology in bacterial meningitis.
Figure 3: Causes of raised intracranial pressure in a patient with bacterial meningitis.
Figure 4: Targets for therapeutic intervention in the immune response to bacterial meningitis.

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Acknowledgements

We thank Dr E Aronica for her help with Figure 1.

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Authors and Affiliations

  1. neurologist at the Academic Medical Center, Center of Infection and Immunity Amsterdam, University of Amsterdam, The Netherlands, and a visiting scientist at the Mayo Clinic College of Medicine, Rochester, MN, USA

    Diederik van de Beek

  2. resident in neurology and J de Gans is a neurologist at the Academic Medical Center, University of Amsterdam,

    Martijn Weisfelt & Jan de Gans

  3. Chair of the Department of Internal Medicine at Monmouth Medical Center in Long Branch, NJ, USA, and Professor of Medicine at Drexel University College of Medicine in Philadelphia, PA, USA

    Allan R Tunkel

  4. Chair of the Division of Critical Care Neurology at the Mayo Clinic College of Medicine, Rochester, MN, USA

    Eelco FM Wijdicks

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Correspondence to Diederik van de Beek.

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van de Beek, D., Weisfelt, M., de Gans, J. et al. Drug Insight: adjunctive therapies in adults with bacterial meningitis. Nat Rev Neurol 2, 504–516 (2006). https://doi.org/10.1038/ncpneuro0265

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