Clinical Review - Bacterial meningitis

Contributed by Dr Nuria Martinez-Alier, a paediatric consultant locum in infectious diseases/immunology at Evelina Children's Hospital, St Thomas' Hospital, London.

Lumbar puncture is the gold standard test for bacterial meningitis
Lumbar puncture is the gold standard test for bacterial meningitis

Section 1: Epidemiology and aetiology
Bacterial meningitis can be a life-threatening emergency.

GPs should have a low threshold for referral and aim for early diagnosis and treatment.

Aetiology
Annual incidence of acute bacterial meningitis (ABM) is estimated at 0.5-5 per 100,000 people in the western world with 30-50 per cent of survivors suffering permanent sequelae.

ABM is one of the top 10 causes of infection-related mortality worldwide. The causative agent can be predicted by the age of the patient and predisposing factors. Neisseria meningitidis and Streptococcus pneumoniae account for 80 per cent of cases in immunocompetent patients.

Meningitis caused by Haemophilus influenzae type b is rare since routine childhood vaccination was initiated and childhood meningitis caused by Strep pneumoniae has reduced with the introduction of pneumococcal conjugate vaccines.

Herd immunity to Strep pneumoniae in the adult population secondary to the infant conjugate vaccine vaccination programme has led to fewer cases of invasive pneumococcal disease in the elderly.

Invasive infections caused by N meningitidis serogroup C are rare, although meningitis due to N meningitidis serogroup B continues to prevail, with a peak in incidence during the winter of 2008/9.

As a consequence of routine infant vaccination programmes, the age-specific incidence of bacterial meningitis has dropped in children, thus increasing the fraction of patients that are adults.

In newborns, group B streptococcal bacteria, Escherichia coli and Listeria monocytogenes can cause meningitis; premature babies and those weighing less than 2kg are at highest risk.

Risk factors
In immunocompromised patients (asplenia, bone marrow insufficiency/suppression, immunodeficiency), the most common causes of ABM are Strep pneumoniae, L monocytogenes and gram-negative bacilli, including salmonella, Klebsiella, enterobacter and Pseudomonas aeruginosa.

Infection with more than one organism typically accounts for 1 per cent of all cases of ABM.

Section 2: Diagnosis
Medical history is crucial in the evaluation of a patient with suspected meningitis. Vaccination history, infectious contacts, immunosuppression history, past infective history (recurrent sinusitis/otitis media), surgical history (ventriculoperitoneal shunt), antibiotic history (partially treated meningitis) and travel history (TB contacts) will all help in assessing the patient.

Symptoms
Early diagnosis and effective antibiotic treatment remains the cornerstone of successful management of ABM. The timeframe between the initial onset of symptoms and phase one of the pathophysiological response to disease is unclear.

The aim is to make a diagnosis and treat in a timeframe of three hours, from diagnosis to antibiotic therapy, before the onset of phase two (see link below).

Patients with meningitis may present with the classic triad of fever, stiff neck and headache; however, in a number of studies these symptoms have only been present in two thirds of adult/adolescent patients with ABM.

Fever was the most common finding (95 per cent) and at least one element of the classic triad was found in every single patient with meningitis. The presentation may be of meningitis or meningitis with septicaemia (see box right).

Presenting symptoms are age dependent. The first symptoms of meningitis may be non- specific and can be mistaken for a common viral illness. However, individuals become seriously ill within hours.

Signs
A high index of suspicion is required for ABM diagnosis.

Physical examination findings that support a diagnosis of ABM include tachycardia, tachypnoea, a positive Kernig's sign, reduced capillary refill time, generalised or focal abnormal neurology, hyper or hypotension, rash and papilloedema.

Investigations
The gold standard investigation to confirm bacterial meningitis is lumbar puncture. Therefore, early and rapid referral to hospital is essential.

If a diagnosis of septicaemia is part of the clinical picture, a blood culture at the GP practice is indicated followed by immediate administration of IM antibiotics. Lack of blood culture facilities should not delay administration of IM antibiotics by the GP in cases of suspected septicaemia.

In addition to lumbar puncture (including cerebrospinal fluid cell count, Gramstain, glucose level, protein level and cytospin), other investigations include: blood culture, inflammatory markers, FBC, clotting profile, renal and liver profile, glucose level, blood gas, urine and serum for rapid bacterial antigen testing, chest X-ray if respiratory compromise (patient may develop an aspiration pneumonia secondary to reduced level of consciousness/seizures) and neuroimaging.

Neuroimaging may also rule out other diagnoses, such as space occupying lesion.

Before a lumbar puncture, brain imaging may be indicated to exclude raised intracranial pressure and reduce the risk of brainstem herniation secondary to lumbar puncture - there is ongoing controversy as to whether this in necessary.

The classification of patients as low risk for complications after lumbar puncture when they lack clinical features related to raised intracranial pressure/focal pathology is a reasonable approach to this difficult decision.

Section 3: Management
Once the aetiological organism has been identified and antibiotic sensitivities are available, antibiotics therapy should be adjusted accordingly.

Adjunct therapy with IV steroids (dexamethasone) is recommended in pneumococcal meningitis to reduce the likelihood of long-term sequelae, particularly deafness.

Duration of treatment varies depending on organism, age and predisposing factors. Consultation with an infectious diseases specialist is recommended.

Preventative treatment for close contacts
Bacterial meningitis is a notifiable disease. This means the UK Health Protection Agency (HPA) should be notified immediately (by the GP, hospital doctor or microbiologist) of any case where there is a high index of suspicion.

Once a firm diagnosis is made and an organism has been identified, the HPA evaluates the case and decide any further action.

The purpose of notifying bacterial meningitis is twofold:

  •  Infection containment: preventive treatment or postexposure vaccination of close contacts (most aetiological agents of bacterial meningitis are transmitted between close contacts through carriage in the nasopharynx, for example N meningitidis, Strep pneumoniae), identification of infectious source (for example monocytogenes is often but not exclusively acquired from unpasteurised soft cheeses) and elimination of any potential infectious foci to avoid an infectious outbreak.
  • Epidemiology of disease: establish vaccine efficacy, vaccine failures, prevalent serotypes, antibiotic resistance patterns and seasonal patterns.

In addition, bacterial meningitis caused by N meningitidis should trigger preventive antibiotic treatment of close contacts to avoid further cases and an outbreak. A case of N meningitidis serogroup C may trigger a vaccination campaign, particularly if the index case is an adolescent and attends college or another institution.

A case of N meningitidis serogroup W135 may trigger an investigation seeking any imported cases from pilgrims to Mecca (where it is known as a source of yearly Hajj associated outbreaks).

Section 4: Prognosis
The prognosis of bacterial meningitis depends on the aetiology, the severity of disease and the time to treatment.

In those with severe bacterial meningitis or a rapid onset of illness, the death rate can be as high as 90 per cent. Survivors have a 25 to 60 per cent risk of long-term disabilities including deafness, seizures, paralysis, blindness or loss of limbs.

In those with less severe cases of bacterial meningitis, the death rate can still approach 25 per cent. Long-term disabilities are possible. A prolonged period of IV antibiotic treatment may be necessary.

Complications
Acute complications of bacterial meningitis include hydrocephalus and subdural collections/empyema.

Hydrocephalus may also develop late once treatment has been completed and there may be the need for neurosurgical intervention.

All survivors of bacterial meningitis require long-term follow-up, audiology review, neurological/neuropsychological assessment and support.

New developments
Recent advances in experimentally induced bacterial meningitis in animals include the role of oxygen-glucose deprivation of hippocampal neurons as a complication of meningitis, the role of cytokines, and the protective roles of nuclear factor-B1 and brain-derived neurotrophic factor. Although such advances are promising, it is unlikely that additional adjunctive therapies will be studied in controlled trials in patients with bacterial meningitis.

Progress is more likely to come from investigations into preventive measures, especially the use of available vaccines and the development of new vaccines.

Meningitis caused by H influenzae type B has been nearly eliminated in the western world since routine vaccination with the H influenzae type B conjugate vaccine was initiated.

The introduction of conjugate vaccines against Strep pneumoniae has substantially reduced the burden of childhood pneumococcal meningitis and has produced herd immunity among adults.

The approval in 2005 of a conjugate quadrivalent meningococcal vaccine against serogroups A, C, Y and W135 is also an important advance that may decrease the incidence of this devastating infection worldwide.

Ongoing vaccine trials with a new generation protein-based meningococcal serogroup B vaccine are promising and in combination with licensed vaccines against serogroups A, C, Y and W135 should lead to significant reduction in the burden of N meningitidis disease.

Resources

  • Fitch MT, van de Beek D. Emergency diagnosis and treatment of adult meningitis. Lancet Infect Dis 2007; 7: 191-200.
  • Van de Beek de Gans J, Tunkel AR et al, Community-Acquired bacterial meningitis in Adults. N Engl J Med 2006; 354: 44-53.
  • Chaudhuri A. Martinez-Martin P, Kennedy PG, et al, EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFMS Task Force on acute bacterial meningitis in older children and adults. Eur J Neurol 2008; 15: 649-59.

Other resources

This topic falls under section 15.7 of the RCGP curriculum 'Neurological problems'

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