Elsevier

The Lancet

Volume 361, Issue 9375, 21 June 2003, Pages 2139-2148
The Lancet

Seminar
Bacterial meningitis in children

https://doi.org/10.1016/S0140-6736(03)13693-8Get rights and content

Summary

This review comprises aspects of the epidemiology, microbiology, pathophysiology, clinical manifestations, diagnosis, management, prognosis, and prevention of bacterial meningitis, with emphasis on the paediatric population. The beginning of this millennium has witnessed the virtual disappearance of Haemophilus invasive disease in some countries, emergence of pneumococcal strains that are resistant to multiple antibiotics, isolation of pneumococci with tolerance to vancomycin, outbreaks and clusters of meningococcal meningitis in several geographical areas, and intense research in development of effective conjugate pneumococcal and meningococcal vaccines. Bacterial meningitis has become an uncommon disease in the developed world. Unfortunately, because of limited economic resources and poor living conditions, many developing countries are still affected by the devastating consequences of this life-threatening systemic infection. Basic and clinical research is needed to discover new antimicrobial and antiinflammatory agents to improve outcome from disease. Novel strategies are needed to distribute and implement effective vaccines worldwide to prevent bacterial meningitis.

Section snippets

Bacteriology

A wide range of bacteria cause purulent meningitis. In the neonatal period, which includes premature and term babies up to 3 months of life, group B streptococci cause most bacterial meningitis in many developed countries.15 Most cases are caused by subtype III strains, and the disease usually arises after the first week of life. Coliform bacilli are the second most common meningeal pathogens in this population, especially strains of Escherichia coli possessing K1 antigen. In many developing

Epidemiology

The frequency of neonatal meningitis varies greatly between different institutions and geographical areas, with rates of about two to ten cases per 10 000 livebirths.25 More than two-thirds of all cases of neonatal meningitis in developed countries are caused by group B streptococci and gramnegative enteric bacilli. L monocytogenes is encountered occasionally, and is usually associated with maternal infection acquired from contaminated milk products. In developing countries, gram-negative

Pathogenesis

Meningitis usually follows invasion of the bloodstream by organisms that have colonised mucosal surfaces. In the neonatal period, pathogens are acquired mainly, although not exclusively, during birth by contact and aspiration of intestinal and genital tract secretions from the mother. Neonates with longer nursery stays can also be exposed to multiple nosocomial pathogens.

In infants and children, meningitis usually develops after encapsulated bacteria that have colonised the nasopharynx are

Pathophysiology

The intense inflammation within the subarachnoid space noted in lumbar CSF, and the resulting neurological damage, are not the direct result of the pathogenic bacteria but rather of activation of the host's inflammatory pathways by the microorganisms or their products (figure).4 When the pathogens have entered the central nervous system, they replicate rapidly and liberate active cell wall or membraneassociated components—ie, lipoteichoic acid and peptidoglycan fragments of gram-positive

Clinical manifestations

The clinical picture of acute bacterial meningitis mainly depends on the patient's age. The classic manifestations noted in older children and adults are rarely present in infants. In general, the younger the patient, the more subtle and atypical are the signs and symptoms. Classic meningitis of children and adults usually begins with fever, chills, vomiting, photophobia, and severe headache. Occasionally, the first sign of illness is a convulsion that can recur during progression of the

Diagnosis

A definitive diagnosis of meningitis is dependent on examination and culture of CSF. Whenever the physician suspects meningitis, a lumbar puncture should be undertaken. Early diagnosis followed by appropriate medical management can have a favourable effect on outcome. In neonates, the procedure should be considered when sepsis is suspected, because meningitis accompanies sepsis in 20–25% of cases. In infants, fever and convulsions may be the only initial signs of meningitis.

When focal

Complications

Complications of acute bacterial meningitis can develop early in the course of illness, either before diagnosis or several days after starting treatment. Systemic circulatory problems usually arise during the first day in hospital with acute bacterial meningitis. Peripheral circulatory collapse is one of the most striking and serious complications of meningitis. It is most frequently associated with meningococcaemia, but can accompany other types of infection.38 Profound shock usually develops

Prognosis

The outlook in individual patients with bacterial meningitis is correlated with many factors, including age of patient, time and clinical stability before effective antibiotic treatment is begun, type of microorganism, number of bacteria or quantity of active bacterial products in CSF at the time of diagnosis, intensity of the host's inflammatory response, and time elapsed to sterilise CSF cultures.4, 32, 54, 55

As a rule, patients at the extremes of age have the poorest outlook. The highest

Antimicrobials

Choice of antibiotic treatment entails the selection of agents that are effective against the probable pathogens and are able to attain adequate bactericidal activity in CSF.19, 65, 66 The estimated bactericidal power of various antimicrobial drugs in CSF cultures has been extrapolated to man from calculation of different pharmacokinetic and pharmacodynamic variables (panel 1). The initial empiric regimen chosen for treatment should be broad enough to cover the potential organisms for the age

Vaccination

Immunisation is the most effective means of prevention of bacterial meningitis in children. Before vaccination, 60–70% of all H influenzae meningitis cases were in infants younger than 18 months old. The new conjugated Haemophilus vaccines are much more immunogenic than the polysaccharide vaccine, and findings of studies in Finland and in the USA show excellent immunogenicity and protection after initiation of a four-dose (three primary and one booster dose) vaccine regimen at 2–3 months of age.

Future challenges

In the past decade, two major advances were accomplished in the field of bacterial meningitis: an improved understanding of the basic mechanisms of disease, and the virtual elimination of Haemophilus meningitis as a result of universal vaccination programmes. Nevertheless, important challenges remain to be solved. We need to assess new antimicrobial agents that are effective against resistant and tolerant pneumococcal strains. More importantly, new candidate vaccines against the most important

Search strategy

We searched MEDLINE database for articles published within the past 15 years, with the keywords meningitis, bacterial meningitis, meningitis in children, bacterial meningitis in children, neuroinfection, CNS infection, brain infection, and meningeal inflammation. We also assessed classic and wellaccepted older articles. We assessed articles in the English and Spanish languages, and articles published in German, French, Asiatic, Arabic, and other journals, with abstracts in the English language.

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