Bacterial meningitis: new therapeutic approaches

Abstract

Bacterial meningitis remains a disease with high mortality and long-term morbidity. Outcome critically depends on the rapid initiation of effective antibiotic therapy. Since a further increase of the incidence of pathogens resistant to antibacterials can be expected both in community-acquired and nosocomial bacterial meningitis, the choice of an optimum initial empirical antibiotic regimen will gain significance. In this context, the use of antibiotics which are bactericidal but do not lyse bacteria, may emerge as a therapeutic option. Conversely, the role of corticosteroids, which decrease the entry of hydrophilic antibacterials into the cerebrospinal fluid, as adjunctive therapy will probably decline as a consequence of the increasing antibiotic resistance of bacteria causing meningitis. Consequent vaccination of all children at present is the most efficient manner to reduce disease burden.

Keywords::

• ampicillin
• ceftriaxone
• clindamycin
• complement
• daptomycin
• glycerol
• hypothermia
• linezolid
• Listeria monocytogenes
• monoclonal antibodies
• Neisseria meningitidis
• rifampicin
• seliciclib
• Streptococcus pneumoniae
• vancomycin

Acknowledgements

The authors thank Sparkasse Göttingen and Dr. Dr. H Wagner, Göttingen, for their continuous support of their work.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Rapid initiation of a bactericidal antibiotic regime remains the cornerstone of treatment of community- and hospital-acquired bacterial meningitis.

• • Clinical symptoms in the very young, in old and in comatose persons can be ambiguous. Here nuchal rigidity often is absent, and mental obtundation or confusion can be the predominating symptom. Rapid diagnosis in these conditions depends on lumbar puncture.

• • Septic shock has to be treated with sufficient amounts of fluid and cautious administration of catecholamines.

• • When clear signs of hydrocephalus are visible on cranial computer tomography, we recommend placement of an external ventriculostomy or (in the case of obvious communicating hydrocephalus) repeated lumbar punctures to lower the elevated intracranial pressure.

• • Adjunctive dexamethasone is recommended for community-acquired bacterial meningitis by most guidelines in developed countries.

• • Adjunctive dexamethasone is not effective under the conditions of developing countries. Whether it is effective in nosocomial meningitis, is unknown.

• • In spite of promising initial results, oral glycerol and therapeutic hypothermia appear ineffective as adjunctive therapies for bacterial meningitis.

• • Among therapeutic options effective in animal models, antibiotic combinations including bactericidal non-bacteriolytic antibiotics, and adjunctive treatment with agents to selectively influence the inflammatory cascade are the most promising candidates for randomized clinical studies to be performed in the near future.

• • The highest impact to reduce disease burden in children in the recent decades originates from the introduction of vaccines against Haemophilus influenzae type B, Streptococcus pneumoniae and Neisseria meningitidis. Until recently, no vaccine was available for N. meningitidis type B, which accounts for 70% of meningococcal infections in Northern Europe. A vaccine to fill this gap has recently been approved in the EU. A reduction of meningococcus type B infections as a consequence of the serogroup B vaccine has not been shown yet, only a sufficient immunological response to the vaccine.

Notes