Paediatric Bacterial Meningitis

Overview

Paediatric bacterial meningitis is a severe life-threatening infection of the central nervous system (CNS) causing an inflammation of the layers surrounding it (meninges). It commonly affects children, particularly neonates under 3 months, it is a notifiable infection in the UK. The five prevalent meningeal pathogens in paediatrics are Streptococcus pneumonia, Haemophilus influenza type b (Hib), Neisseria meningitides, Listeria monocytogenes, and Group B Streptococcus (GBS). Pneumococcal meningitis remains the leading cause of bacterial meningitis in children over one month and is linked to high morbidity and mortality rates, but the overall rates have been reducing since the introduction of vaccines against these pathogens.^1,4

Globally, paediatric bacterial meningitis continues to be a significant neurological incident that requires immediate medical intervention due to developing short and long-term complications with time. These complications are variable depending on age group and infecting organism. Pneumococcal meningitis in children over 1 month old accounts for 70% of cases worldwide and contributes to fewer clinical outcomes.²

Epidemiology

The incidence of bacterial meningitis in Western countries was documented by a 2018 study to be about 0.7 to 0.9 per 100000 people per year. However, since the 1990s, this rate has been reduced by 3% to 4%. In the UK, regardless of aetiology, 2594 cases were reported to have meningitis in children from 2004 to 2011. In African countries, the total incidence was found to be 10-40 per 100000 people per year. In developed countries, the incidence of confirmed bacterial meningitis in newborns via bacterial culture is expected at 0.3 per 1000 live births.³

Aetiology

The causes of paediatric bacterial meningitis depend on several factors. It is dependent on age, geographic location, immune function, immunisation status, and genetics.¹

Aetiology by age group and geographic location 

• S. pneumonia was the most prevalent cause of bacterial meningitis in the “all children group” accounting for a percentage beginning with 22.5% in Europe to 41.1% in Africa
• E.coli and S. pneumonia were the dominant pathogens to cause bacterial meningitis in neonates in Africa accounting for 17.7% and 20.4% respectively
• N.meningitidis was the most common in children in Europe aged between ±1-5 years representing 47.0%
• In children aged ±6-18 years, S.pneumoniae is the leading cause of bacterial meningitis

Aetiology by immune function 

Neonates, infants, and premature infants are the group age at the highest risk of developing bacterial meningitis due to several factors linked to immune status. After 32 weeks gestation, the maternal immunoglobulins cross via the placenta to the baby, therefore premature babies may not receive enough maternal immunoglobulins to cause secondary immature immune function and defective phagocytic process of monocytes and neutrophils that helps in fighting bacterial infections. 

Aetiology by immunisation status

Children under 1 year are the group most affected by bacterial meningitis. Mortality rates and complications caused by meningitis pathogens dropped significantly after introducing vaccinations. However, more neurological impairments developed in children who were not vaccinated compared to those who were not vaccinated.¹

Pathophysiology

Meningitis is initiated by pathogen invasion to the CNS either through bacteremia by which the bacteria get access into the blood circulation or from infections like ear infection (sinusitis). In the brain particularly the subarachnoid space, the bacteria multiply causing the activation of the immune process which results in bacterial lysis. This lysis in the presence of bacterial particles triggers further response which is the inflammatory mechanisms characterised by the migration of neutrophils through the blood-brain barrier and continuous release of cytokines and other chemicals. Persistent inflammatory response leads to cerebral edema, higher intracranial pressure, and impaired metabolism contributing to damage to nerve cells and restricted blood flow (ischemia).⁵

Paediatric bacterial meningitis complication

Short term complications

• Seizures
• Subdural effusions (fluid accumulates between the layers covering the brain due to inflammation)
• Focal neurological deficits (impairments in functions controlled by a particular area of the brain)

Long term complications

• Cognitive impairment
• Hearing loss
• Learning disability
• Hydrocephalus (accumulation of excess cerebrospinal fluid leads to elevated pressure inside the skull)
• Epilepsy

Diagnosis

A lumbar puncture (LP) procedure is a key diagnostic tool for bacterial meningitis which involves a needle being inserted into the lower back between the bones of the spine. The procedure is used to examine the cerebrospinal fluid (CSF). Clinical findings in bacterial meningitis are:

• Elevated white blood cell count (leukocytosis), WBC >1000 Cells/µL, particularly polymorphonuclear cells
• Elevated protein levels, >150 mg/dL
• Low glucose levels, <40 mg/dL

However, normal CSF indexes vary with age in the infant population. Culture and Gram stain remain the most essential diagnostic tools for bacterial meningitis. They are affordable tools and reliable but their sensitivity varies depending on three factors which are: prior antibiotic use, pathogen type, and different age groups. 

The sensitivity of Gram stains in children is ranging between 50% to 63% but 60% in neonates. Moreover, sensitivity is the highest for S.pneumoniae and lowest for L.monocytogenes. In regards to antibiotic pre-treatment, it has no impact on Gram stain sensitivity, unlike CSF and blood cultures, which affect their sensitivity by reducing it.¹

Management 

Empirical antibiotic therapy

Administration of empirical antibiotics is a critical phase in covering common bacteria that cause meningitis in children and achieving the targeted concentrations in CSF. Any delays in treatment beyond 6 hours have been associated with complications in infants. 

Neonatal meningitis treatment relies mainly on the combination of ampicillin and cefotaxime or gentamicin. However, due to bacterial resistance, the use of cefotaxime is recommended over gentamicin, in addition to its effectiveness in CSF penetration. 

In children, it is highly recommended to use vancomycin plus cefotaxime or ceftriaxone as an empirical antibiotic therapy for suspected bacterial meningitis in the face of increasing resistance among pneumococcal strains to penicillins and cephalosporins combinations, particularly in the regions of elevated bacterial resistance. 

The precise antibiotic therapy can be used once the specific causing bacteria is confirmed by a suitable diagnostic procedure such as blood culture or Gram Stain, and antimicrobial susceptibility testing is performed. 

Length of therapy

In uncomplicated neonatal meningitis caused by S.pneumoniae, L.monocytogenes, and GBS, the duration of 14 days of antibiotics is adequate. However, 21 days is recommended for Gram-negative bacilli meningitis. 

Regarding children with uncomplicated meningitis, the recommended duration for:

• H. influenzae 7 to 10 days
• N. meningitidis 5 to 7 days
• L. monocytogenes 14 to 21 days 
• Gram-negative bacilli at least 21 days
• S. pneumonia 10 to 14 days

Lengthy antimicrobial courses are significant in complicated meningitis cases, such as brain abscesses, and ventriculitis. 

Adjunctive therapy

Adjunctive therapy in neonatal meningitis with dexamethasone, immunoglobulins, glycerol, and granulocyte-macrophage colony-stimulating factor (GM-CSF) requires further research to support their efficiency, thus they are not recommended in clinical practice. 

In children, studies have demonstrated the effectiveness of the use of dexamethasone besides antibiotics in alleviating serious neurological impairment and hearing loss in wealthy countries, but advantageous outcomes are not guaranteed in low-income countries due to delayed treatment. The efficacy of dexamethasone varies based on the causative pathogen. Despite that, it is recommended to use it in certain cases by the American Academy of Pediatrics (AAP) and Infectious Diseases Society of America (IDSA). 

The use of glycerol as an adjunctive therapy lacks evidence regarding its impact on complicated neurological concerns, hearing loss, and death. 

Supportive care

Serious complications of acute bacterial meningitis such as seizures and septic shock, often appear within the first few days. Therefore, these cases should receive intensive care by closely monitoring their heart and lung functions. In children, cerebral blood flow might reduce due to the swelling and pressure inside the skull. Signs of elevated pressure should be controlled accurately and intubation to be provided if required. 

Prevention

Intrapartum antibiotic prophylaxis (IAP) achieves significant positive outcomes in reducing the early onset of disease but not that of late-onset. Ongoing research is being conducted to develop a vaccine for both of early and late-onset disease which will be achieved by triggering maternal immunity transfer to infants. Moreover, in children, timely vaccination is still the optimal approach to prevent bacterial meningitis. 

Future Perspectives

Bacterial meningitis remains the leading cause of death in children worldwide. More efforts should be implemented to prioritise vaccination adherence and access to most geographic locations against common pathogens. Moreover, enhancing educational programs among healthcare professional teams including screening and treatment during pregnancy, and relying on rapid PCR panels could improve early diagnosis and reduce morbidity and mortality rates. 

Summary

• Paediatric bacterial meningitis is a severe infection of the brain causing the inflammation of the layers surrounding it
• The causes of paediatric bacterial meningitis depend on age, geographic location, immune function, immunisation status, and genetics
• Meningitis begins with pathogen invasion to the CNS either through bacteremia by which the bacteria get access into the blood circulation or from infections
• Complications can be short-term and long-term. Short-term complications can include seizures and long-term complications may include hearing loss
• A lumbar puncture (LP) procedure is a key diagnostic tool for bacterial meningitis to examine CSF
• Culture and gram staining remain the most essential diagnostic tools for bacterial meningitis
• Administration of empirical antibiotics is a critical phase in covering common bacteria that cause meningitis in children
• Adjunctive therapy in neonatal meningitis as dexamethasone, requires further research to support its efficiency, thus they are not recommended
• In children, studies have demonstrated the effectiveness of the use of dexamethasone besides antibiotics in reducing serious neurological impairment but this is not guaranteed in low-income countries due to delayed treatment
• Timely vaccination is still the optimal approach to prevent bacterial meningitis