Review
Acute bacterial meningitis in infants and children

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Summary

Bacterial meningitis continues to be an important cause of mortality and morbidity in neonates and children throughout the world. The introduction of the protein conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has changed the epidemiology of bacterial meningitis. Suspected bacterial meningitis is a medical emergency and needs empirical antimicrobial treatment without delay, but recognition of pathogens with increasing resistance to antimicrobial drugs is an important factor in the selection of empirical antimicrobial regimens. At present, strategies to prevent and treat bacterial meningitis are compromised by incomplete understanding of the pathogenesis. Further research on meningitis pathogenesis is thus needed. This Review summarises information on the epidemiology, pathogenesis, new diagnostic methods, empirical antimicrobial regimens, and adjunctive treatment of acute bacterial meningitis in infants and children.

Introduction

Bacterial meningitis, an inflammation of the meninges affecting the pia, arachnoid, and subarachnoid space that happens in response to bacteria and bacterial products, continues to be an important cause of mortality and morbidity in neonates and children.1, 2, 3, 4 However, mortality and morbidity vary by age and geographical location of the patient and the causative organism. Patients at risk for high mortality and morbidity include newborns, those living in low-income countries, and those infected with Gram-negative bacilli and Streptococcus pneumoniae.1, 2, 3, 4 Severity of illness on presentation (eg, low score on Glasgow coma scale), infection with antimicrobial-resistant organisms, and incomplete knowledge of the pathogenesis of meningitis are additional factors contributing to mortality and morbidity associated with bacterial meningitis.1, 2, 3, 4, 5, 6, 7

Suspected bacterial meningitis is a medical emergency; thus, immediate steps must be taken to establish the specific diagnosis, and empirical antimicrobial treatment must be started rapidly. The mortality of untreated bacterial meningitis approaches 100% and, even with optimum treatment, mortality and morbidity might happen. Neurological sequelae are relatively common in survivors of meningitis, particularly after pneumococcal meningitis.1, 2, 3, 4, 5, 6

Section snippets

Epidemiology

Almost all microbes that are pathogenic to human beings have the potential to cause meningitis, but a relatively small number of pathogens (ie, group B streptococcus, Escherichia coli, Listeria monocytogenes, Haemophilus influenzae type b [Hib], S pneumoniae, and Neisseria meningitidis) account for most cases of acute bacterial meningitis in neonates and children, although the reasons for this association remain incompletely understood.

The absence of an opsonic or bactericidal antibody is a

Pathogenesis

A relatively small number of microbial pathogens has been shown to account for most cases of meningitis in infants and children, but how those pathogens cross the blood–brain barrier and cause meningitis is incompletely understood.7, 19 Experimental animal models and human cases of meningitis suggest that E coli and group B streptococcus penetrate the brain initially through the cerebral vasculature.20, 21, 22, 23 The blood–brain barrier is a structural and functional barrier that is formed by

Clinical findings

Bacterial meningitis requires early diagnosis and empirical antimicrobial treatment. However, the symptoms and signs depend on the age of the child, the duration of illness, and the host response to infection. The clinical features of bacterial meningitis in infants and children can be subtle, variable, non-specific, or even absent. In infants, they might include fever, hypothermia, lethargy, irritability, poor feeding, vomiting, diarrhoea, respiratory distress, seizures, or bulging

Antimicrobial treatment

Eradication of the infecting organism from the CSF is entirely dependent on antibiotics, and bactericidal antibiotics should be administered intravenously at the highest clinically validated doses to patients with suspected bacterial meningitis.96, 97 Several retrospective and prospective studies showed that delay in antibiotic treatment was associated with adverse outcomes.98, 99, 100, 101 In patients with suspected bacterial meningitis for whom immediate lumbar puncture is delayed due to

Adjunctive treatment

Neurological sequelae are common in survivors of meningitis, and include hearing loss, cognitive impairment, and developmental delay. For example, the Metropolitan Atlanta Developmental Disabilities Surveillance Program in 1991 identified bacterial meningitis as the leading postnatal cause of developmental disabilities, including cerebral palsy and mental retardation.126 Hearing loss happens in 22–30% of survivors of pneumococcal meningitis compared to 1–8% after meningococcal meningitis.6, 96,

Future challenges

Bacterial meningitis continues to be an important cause of mortality and morbidity throughout the world, particularly for those infections in newborns, individuals living in low-income countries, and infections caused by antimicrobial-resistant pathogens (eg, cephalosporin-resistant pneumococcus) or organisms that are difficult to treat (eg, multi-resistant Gram-negative bacilli). Success with the protein-conjugate Hib and S pneumococcus PCV vaccines in the prevention of meningitis shows that

Search strategy and selection criteria

The information for this Review was identified by searches of Medline in June, 2009 (date limits January, 2000, to June, 2009), with the following search terms (alone and in combination): “neonatal bacterial meningitis”, “bacterial meningitis in infants and children”, “pathogenesis of bacterial meningitis”, “microbial invasion and/or traversal of the blood–brain barrier”, “diagnosis of bacterial meningitis”, “treatment of bacterial meningitis”, and “adjunct therapy of bacterial

References (135)

  • HH Niemann et al.

    Structure of the human receptor tyrosine kinase Met in complex with the Listeria invasion protein InlB

    Cell

    (2007)
  • MA Reddy et al.

    Phosphatidylinositol 3-kinase activation and interaction with focal adhesion kinase in E coli K1 invasion of human brain microvascular endothelial cells

    J Biol Chem

    (2000)
  • S Shin et al.

    RhoA and Rac1 contribute to type III group B streptococcal invasion of human brain microvascular endothelial cells

    Biochem Biophys Res Commun

    (2006)
  • N Chiba et al.

    Rapid detection of eight causative pathogens for the diagnosis of bacterial meningitis by real-time PCR

    J Infect Chemother

    (2009)
  • R Ben et al.

    Rapid diagnosis of bacterial meningitis using a microarray

    J Formos Med Assoc

    (2008)
  • F Dubos et al.

    Sensitivity of the bacterial meningitis score in 889 children with bacterial meningitis

    J Pediatr

    (2008)
  • JR Miner et al.

    Presentation, time to antibiotics, and mortality of patients with bacterial meningitis at an urban county medical center

    J Emerg Med

    (2001)
  • G Klinger et al.

    Predicting the outcome of neonatal bacterial meningitis

    Pediatrics

    (2000)
  • JP Stevens et al.

    Long-term outcome of neonatal meningitis

    Arch Dis Child Fetal Neonatal Ed

    (2003)
  • J de Louvois et al.

    Neonatal meningitis in England and Wales: sequelae at 5 years of age

    Eur J Pediatr

    (2004)
  • I Roine et al.

    Influence of admission findings on death and neurological outcome from childhood bacterial meningitis

    Clin Infect Dis

    (2008)
  • M Arditi et al.

    Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use

    Pediatrics

    (1998)
  • KS Kim

    Pathogenesis of bacterial meningitis: from bacteremia to neuronal injury

    Nat Rev Neurosci

    (2003)
  • LD Fothergill et al.

    Influenzal meningitis: the relation of age incidence to the bactericidal power of blood against the causal organism

    J Immunol

    (1933)
  • DS Chudwin et al.

    Effect of antibody concentration on opsonic requirements for phagocytosis in vitro of Streptococcus pneumoniae types 7 and 19

    Proc Soc Exp Biol Med

    (1983)
  • I Goldschneider et al.

    Human immunity to the meningococcus. I. The role of humoral antibodies

    J Exp Med

    (1969)
  • CJ Baker et al.

    Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection

    N Engl J Med

    (1976)
  • DE Schiff et al.

    Estimation of protective levels of anti-O-specific lipopolysaccharide immunoglobulin G antibody against experimental Escherichia coli infection

    Infect Immun

    (1993)
  • H Peltola

    Worldwide Haemophilus influenzae type b diseases at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates

    Clin Microbiol Rev

    (2000)

  • Progress toward elimination of Haemophilus influenza type b invasive disease among infants and children—United States, 1998–2000

    MMWR Morb Mortal Wkly Rep

    (2002)
  • CG Whitney et al.

    Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine

    N Engl J Med

    (2003)
  • CJ Tsai et al.

    Changing epidemiology of pneumococcal meningitis after the introduction of pneumococcal conjugate vaccine in the United States

    Clin Infect Dis

    (2008)
  • HE Hsu et al.

    Effect of pneumococcal conjugate vaccine on pneumococcal meningitis

    N Engl J Med

    (2009)
  • WR Borrow et al.

    Long-term protection in children with meningococcal C conjugate vaccination: lessons learned

    Expert Rev Vaccines

    (2006)
  • KS Kim

    Mechanisms of microbial traversal of the blood–brain barrier

    Nat Rev

    (2008)
  • PH Berman et al.

    Neonatal meningitis. A clinical and pathological study of 29 cases

    Pediatrics

    (1966)
  • P Ferrieri et al.

    Production of bacteremia and meningitis in infant rats with group B streptococcal serotypes

    Infect Immun

    (1980)
  • KS Doran et al.

    Blood–brain barrier invasion by group B streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid

    J Clin Invest

    (2005)
  • KS Kim et al.

    The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat

    J Clin Invest

    (1992)
  • LL Rubin et al.

    The cell biology of the blood–brain barrier

    Annu Rev Neurosci

    (1999)
  • SH Huang et al.

    E coli invasion of brain microvascular endothelial cells in vitro and in vivo: molecular cloning and characterization of E coli invasion gene ibe10

    Infect Immun

    (1995)
  • V Nizet et al.

    Invasion of brain microvascular endothelial cells by group B streptococci

    Infect Immun

    (1997)
  • A Ring et al.

    Pneumococcal trafficking across the blood–brain barrier. Molecular analysis of a novel bi-directional pathway

    J Clin Invest

    (1998)
  • A Unkmeir et al.

    Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells

    Mol Microbiol

    (2002)
  • NA Khan et al.

    Outer membrane protein A and cytotoxic necrotizing factor-1 use diverse signaling mechanisms for Escherichia coli K1 invasion of human brain microvascular endothelial cells

    Microb Pathog

    (2003)
  • D Cabanes et al.

    gp96 is a receptor for a novel Listeria monocytogenes virulence factor, Vip, a surface protein

    EMBO J

    (2005)
  • CJ Orihuela et al.

    Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models

    J Clin Invest

    (2009)
  • S Gauczynski et al.

    The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein

    EMBO J

    (2001)
  • GV Ludwig et al.

    A putative receptor for Venezuelan equine encephalitis virus from mosquito cells

    J Virol

    (1996)
  • C Thepparit et al.

    Serotype-specific entry of dengue virus into liver cells: identification of the 37-kilodalton/67-kilodalton high-affinity laminin receptor as a dengue virus serotype 1 receptor

    J Virol

    (2004)

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