Elsevier

The Lancet Neurology

Volume 5, Issue 4, April 2006, Pages 332-342
The Lancet Neurology

Review
Pneumococcal meningitis in adults: new approaches to management and prevention

https://doi.org/10.1016/S1474-4422(06)70409-4Get rights and content

Summary

Since the virtual eradication of meningitis due to Haemophilus influenzae type B by vaccination in the developed world, pneumococcal meningitis has become the leading cause of bacterial meningitis beyond the neonatal period. Clinical and experimental research has increased our knowledge about the pathophysiology and pathogenesis of the disease over the past decades. Despite the availability of effective antibiotics, supportive care facilities, and recent advances in adjunctive strategies—ie, adjunctive dexamethasone—mortality and morbidity rates associated with pneumococcal meningitis remain unacceptably high. Although preliminary results after the introduction of the pneumococcal conjugate vaccine are promising, the incidence of multidrug-resistant pneumococcal strains is rising worldwide. Here we discuss clinical aspects of pneumococcal meningitis in adults, with focus on pathophysiology, and stress the urgent need for adequate preventive measures and new effective treatments.

Introduction

Acute bacterial meningitis is a life-threatening infectious disease. The annual incidence is estimated at 2·6–6 cases per 100 000 population and could be ten times higher than this in less developed countries.1, 2 Vaccination strategies have substantially changed the epidemiology of bacterial meningitis during the past two decades.3 Routine vaccination of children against Haemophilus influenzae type B has virtually eradicated bacterial meningitis due to this bacterium in the developed world.1, 4 As a consequence, Streptococcus pneumoniae has become the most common pathogen—ie, cause of bacterial meningitis—beyond the neonatal period.5 Today, despite advances in medical care, mortality from pneumococcal meningitis ranges from 16% to 37% and neurological sequelae are estimated to occur in 30–52% of surviving adults.6, 7, 8 Previously we described clinical characteristics and prognostic factors in adults with pneumococcal meningitis in a large prospective cohort study.6 In the current review we summarise clinical and diagnostic aspects of the disease in adults, and focus on current understandings of the pathophysiology and pathogenic mechanisms associated with pneumococcal meningitis. Finally, we discuss advances in current and future therapeutic strategies, and challenges for future research.

Section snippets

Clinical features

Several retrospective studies have assessed the clinical characteristics of pneumococcal meningitis in adults. Many studies included both children and adults with various causative pathogens.7, 8, 9, 10, 11, 12, 13, 14, 15 In 2004, results were presented from the Dutch Meningitis Cohort Study, a prospective nationwide observational cohort study in the Netherlands.16 We provided a detailed description of the clinical course, spectrum of complications, prognostic factors, and outcome in 352

Pathogenesis of pneumococcal meningitis

Understanding the interactions between bacteria and host is essential in the development of new therapeutic strategies for pneumococcal meningitis.2 During the past decades research has focused on the pathogenesis of the disease. The CNS is protected against microbial entry from the bloodstream by the blood–brain barrier and by an external barrier that is formed by the leptomeninges and skull.36 As a consequence, either the pathogen enters the CNS via the bloodstream or by direct invasion

Potential future adjuvant therapeutic strategies

Several mediators contribute to the migration of leucocytes across the blood–brain barrier (pleocytosis) and increased permeability of the blood–brain barrier during bacterial meningitis. Down-regulation of these mediators and targeting of pathways involved in the induction of neuronal injury are promising adjuvant therapeutic strategies for bacterial meningitis.42 Table 5 summarises potential treatment strategies that are currently being explored in studies with specific inhibitors and

Antibiotic resistance

The increase of drug-resistant pneumococci has become an emerging problem worldwide.19, 76, 77 Depending on geographic region, the prevalence of antibiotic-resistant strains in the USA is as high as 35%.76 Penicillin resistance in pneumococci often coincides with decreased susceptibility to other antimicrobial agents, and treatment failures in meningitis as a result of multidrug-resistant bacteria have been reported.77 Although management of drug-resistant infections is one of the most

Vaccination

Current pneumococcal vaccines elicit immune responses to cell-wall polysaccharides of pneumococci. The current 23-valent pneumococcal polysaccharide vaccine contains capsular polysaccharides of 23 serotypes responsible for about 90% of invasive pneumococcal infections.82 In the USA, the vaccine is recommended for all people aged 65 years and older and for those aged between 2 years and 64 years who are at increased risk for invasive pneumococcal disease because of underlying illnesses, such as

Future research

S pneumoniae meningitis is a disease with many challenges for future research. What will be the effect of the increasing emergence and spread of multidrug-resistant strains on future antibiotic efficacy? Could vaccination strategies be beneficial in reversing antibiotic-resistance in S pneumoniae and what will be the effect of new-generation pneumococcal vaccines? What is the effect of routine use of adjunctive dexamethasone therapy in patients with bacterial meningitis and do steroids affect

Search strategy and selection criteria

References for this review were published between 1969 and December 2005, and identified by searches of MEDLINE and PubMed and from relevant papers. The search terms used were: “S pneumoniae”, “bacterial meningitis”, “pneumococcal meningitis”, “pathophysiology”, “pathogenic mechanisms”, “antibiotic-resistance”. Only papers in English were reviewed and abstracts and reports from meetings were not included. The final reference list was generated from papers that were original and relevant

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