Bacterial meningitis: an update of new treatment options

Abstract

The outcome of bacterial meningitis critically depends on the rapid initiation of bactericidal antibiotic therapy and adequate management of septic shock. In community-acquired meningitis, the choice of an optimum initial empirical antibiotic regimen depends on the regional resistance patterns. Pathogens resistant to antibacterials prevail in nosocomial bacterial meningitis. Dexamethasone is recommended as adjunctive therapy for community-acquired meningitis in developed countries. In comatose patients, aggressive measures to lower intracranial pressure <20 mmHg (in particular, external ventriculostomy, osmotherapy and temporary hyperventilation) were effective in a case–control study. Although many experimental approaches were protective in animal models, none of them has been proven effective in patients. Antibiotics, which are bactericidal but do not lyse bacteria, and inhibitors of matrix metalloproteinases or complement factor C5 appear the most promising therapeutic options. At present, vaccination is the most efficient method to reduce disease burden. Palmitoylethanolamide appears promising to enhance the resistance of the brain to infections.

Keywords:

• ampicillin
• cefepime
• ceftazidime
• ceftriaxone
• clindamycin
• complement
• daptomycin
• eritoran
• glycerol
• hypothermia
• immunotherapy
• linezolid
• Listeria monocytogenes
• monoclonal antibodies
• n-acetylcysteine
• Neisseria meningitidis
• palmitoylethanolamide
• paracetamol
• resveratrol
• rifampicin
• seliciclib
• Streptococcus pneumoniae
• vancomycin

Acknowledgement

This work is an updated version of the publication, Nau R, Djukic M, Spreer A, Eiffert H, Bacterial meningitis: new therapeutic approaches. Expert Rev Anti Infect Ther 2013;11:1079-95.

Financial & competing interests disclosure

This work was supported by Sparkasse Göttingen. The authors have no commercial interests in the contents of this manuscript. The authors have no other 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 apart from those disclosed.

Key issues

The grade of evidence is given in brackets (class 1: evidence from at least one properly designed randomized controlled trial; class 2: evidence from at least one well-designed clinical trial, without randomization, or from cohort studies; class 3: evidence from opinions of authorities, based on clinical experience, or from descriptive case studies).

• Rapid initiation of a bactericidal antibiotic regimen and adequate management of septic shock remain the cornerstone of the treatment of community- and hospital-acquired bacterial meningitis (class 2).

• 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 (class 2).

• Rapid diagnosis relies on lumbar puncture (class 2).

• Septic shock has to be treated with sufficient amounts of fluid and cautious administration of catecholamines (class 2).

• When clear signs of hydrocephalus are visible on cranial computer tomography, placement of an external ventriculostomy or (in the case of obvious communicating hydrocephalus) repeated lumbar punctures to lower the elevated intracranial pressure are indicated (class 2).

• Adjunctive dexamethasone is recommended for community-acquired bacterial meningitis by most guidelines in developed countries (class 1).

• Adjunctive dexamethasone is not effective under the conditions of developing countries (class 1). Whether it is effective in nosocomial meningitis is unknown.

• In spite of promising initial results, oral glycerol and paracetamol showed no clear benefit as adjuncts to antibiotic therapy (class 1).

• Therapeutic hypothermia is ineffective as adjunctive therapy for bacterial meningitis (class 1).

• Among the 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 (class 3).

• 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. Vaccines for N. meningitidis type B, which accounts for 70% of meningococcal infections in northern Europe, are now available (class 2).

• In nosocomial meningitis, in particular, after surgery and placement of ventricular drains, highly resistant bacteria including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and Acinetobacter spp. play an increasing role (class 3).

• Prophylactic antibiotic use in patients with basilar skull fractures, whether there is evidence of cerebrospinal fluid leakage or not, is not indicated (class 1).

• Immunostimulators or immunomodulators may emerge as options to prevent CNS infections in high-risk groups (class 3).

Notes