Meningitis

Meningitis is an inflammation of the leptomeninges and underlying subarachnoid cerebrospinal fluid. It is notifiable in the UK under the Public Health (Infectious Diseases) Regulations 1988.

• Viral infection is the commonest cause.
• The incidence of bacterial meningitis is 2-3 per 100,000; vaccination is successfully reducing haemophilus and meningococcal type C infections, and so patterns of infection are changing:
  • Streptococcus pneumoniae: in all except neonates.
  • Neisseria meningitidis: usually local outbreaks among young adults; increased incidence in late winter or early spring. Meningococcal meningitis is endemic in parts of Africa, India and other developing nations. Periodic epidemics occur in the sub-Saharan Africa as well as among religious pilgrims travelling to Saudi Arabia for the Hajj.
  • Group B streptococci: in newborns.
  • Listeria monocytogenes: in newborns, elderly, and immunocompromised.
  • Haemophilus influenzae, type b in unvaccinated children and adults.
  • Syphilis and tuberculosis are rare causes but are increasing in association with HIV infection.

Risk factors

• Patients with CSF shunts or dural defects (e.g. staphylococcal).
• Patients having spinal procedures (e.g. spinal anaesthetics) are at increased risk and Pseudomonas species may then be the cause.
• Other risk factors include bacterial endocarditis, diabetes mellitus, alcoholism and cirrhosis, intravenous drug abuse, renal insufficiency, adrenal insufficiency, malignancy (increased risk of Listeria infection), hypoparathyroidism, thalassaemia major and cystic fibrosis.
• Splenectomy and sickle cell disease increase the risk of meningitis secondary to encapsulated organisms.
• Crowding (e.g. military recruits and college students) increases the risk of outbreaks of meningococcal meningitis.

Meningitis is caused by the following pathogens in each age group:

• Neonates: Group B beta-haemolytic streptococci, Listeria monocytogenes, Escherichia coli
• Infants and young children: Haemophilus influenzae if younger than 4 years and unvaccinated, meningococcus (Neisseria meningitidis), Streptococcus pneumoniae (Pneumococcus)
• Adults and older children: S.pneumoniae, H.influenzae, N.meningitidis, Gram-negative bacilli, staphylococci, streptococci and Listeria monocytogenes
• Elderly and immunocompromised: Pneumococcus, Listeria monocytogenes, tuberculosis, Gram negative organisms, Cryptococcus
• Hospital acquired and post-traumatic meningitis (may often be multi-drug-resistant), Klebsiella pneumoniae, E.coli, Pseudomonas aeruginosa, Staphylococcus aureus

Aseptic meningitis

CSF has cells but is Gram-stain -ve and no bacteria can be cultured on standard media. Causes include:

• Virus infection (echovirus, mumps, coxsackie, herpes simplex and zoster, HIV, measles, influenza).
• Partly treated bacterial meningitis.
• Other possible causative organisms include fungi, atypical TB, syphilis, Lyme disease, leptospirosis, listeria and brucella.
• Kawasaki disease.

Non-infective meningitis

Meningeal inflammation can be caused by meningeal infiltration by:

• Malignant cells (leukaemia, lymphoma, other tumours)
• Chemical meningitis (intrathecal drugs, contaminants)
• Drugs (NSAIDS, trimethoprim)
• Sarcoidosis
• Systemic lupus erythematosus
• Behcet's disease

Individual symptoms have low diagnostic accuracy. Absence of fever, neck stiffness, and altered mental status makes the diagnosis of meningitis much less likely.
A recent study of children aged 16 years or younger with meningococcal disease found that classical signs such as haemorrhagic rash, meningism and impaired consciousness did not tend to appear until after 13 to 22 hours. However more non-specific features such as leg pain, cold hands and feet and abnormal skin colour appeared much earlier with a median onset of 7-12 hours. These earlier features are therefore very important in early diagnosis and therefore earlier initiation of potentially life-saving treatment.¹

• Approximately 25% of patients with bacterial meningitis present acutely within 24 hours of onset of symptoms.
• Other patients with bacterial meningitis and most patients with viral meningitis present with subacute neurological symptoms developing over 1-7 days.
• Chronic symptoms lasting longer than 1 week suggest meningitis caused by some viruses as well as tuberculosis, syphilis or fungi (especially cryptococci).
• Classic symptoms are not evident in infants and also not often seen in the elderly.
• Prodromal upper respiratory infection symptoms.
• Early red flag symptoms of meningococcal disease:¹
  • Leg pain
  • Cold hands and feet
  • Abnormal skin colour
• Meningism:
  • Headache, photophobia, stiff neck (generally not present in children under the age of one year or in patients with altered mental state)
  • Kernig's sign positive (pain and resistance on passive knee extension with hips fully flexed)
  • Brudzinski's sign positive (hips flex on bending head forward)
  • If severe - opisthotonus
• Raised intracranial pressure:
  • Headache, irritability, drowsiness, vomiting, fits
  • Irregular respiration and tachypnoea
  • Impaired consciousness or coma
  • Pulse reduced; blood pressure increased
  • Papilloedema (late sign)
• Septicaemia:
  • Malaise, fever, arthritis
  • Odd behaviour
  • Rash (petechiae suggest meningococcus or pneumococcus)
• Seizures (30-40% in children, 20-30% in adults)
• Focal neurological symptoms (including focal seizures)
• Infants and young children:
  • Suspect meningitis in any ill baby or child
  • Early features: cold hands and feet, leg pain, abnormal skin colour, poor feeding, vomiting, thirst, diarrhoea, breathing difficulty or unusual crying.¹
  • Classic features: hypotonia, tense fontanelle, photophobia, neck pain or stiffness, haemorrhagic rash.
  • Late features: confusion, seizures, coma.

• Other causes of pyrexia and severe infection
• Intracranial abscess
• Other causes of altered mental state and coma, e.g. subarachnoid haemorrhage, brain tumours

Must not delay treatment

Lumbar puncture

• See separate articles on Lumbar Puncture (LP) and Cerebrospinal Fluid for normal values and interpretation of abnormal CSF findings.
• Do immediately provided no signs of raised intracranial pressure (reduced consciousness, very bad headache, frequent fits) or focal neurology.
• Beware signs of impending brain herniation (abnormal postures or breathing, dilated pupils, doll's eyes reflexes, papilloedema).
• CT scan can rule out a mass lesion or hydrocephalus, but one study suggested it is a poor predictor of herniation.²
• Send 3 bottles of cerebrospinal fluid (CSF) for Gram stain, Ziehl-Nielsen stain (tuberculosis), cytology, virology, glucose, protein, culture, rapid antigen screen or PCR if available and India ink for cryptococcus.
• CSF may be normal early on so repeat the LP if symptoms and signs persist.

Other investigations

• Blood cultures (preferably before antibiotics)
• Blood glucose (to compare with CSF)
• Full blood count, urea, creatinine and electrolytes
• Coagulation profile: especially if disseminated intravascular coagulation is suspected
• Chest x-ray (lung abscess)
• Culture urine, nasal swabs and stool (virology)
• CT scan if history of head injury, altered mental state, focal neurological deficits or concern regarding raised intracranial pressure before LP.
• Other possible investigations:
  • Serum cryptococcal antigen, especially if baseline is known (less diagnostic than India ink and CSF cryptococcal antigen).
  • Serology of blood, urine, and CSF for specific bacterial antigens is occasionally recommended if diagnostic doubt or in patients with partially treated meningitis.
  • Serum test for syphilis if neurosyphilis is suspected.

The listed drug regimes are based on current BNF guidance:³

Initial 'blind' therapy

• Transfer patient urgently to hospital.
• If bacterial meningitis and especially if meningococcal disease suspected, give benzylpenicillin before urgent transfer to hospital. Cefotaxime may be an alternative in penicillin allergy; chloramphenicol may be used if history of anaphylaxis to penicillin or to cephalosporins.
• Third generation cephalosporin (cefotaxime or ceftriaxone) is often used as empirical treatment before identification of causative organism. Ampicillin should be added if Listeria is suspected and particularly for infants under three months old, those aged over 50 years old and immunocompromised individuals.²
• Consider adjunctive treatment with dexamethasone (particularly if pneumococcal meningitis is suspected in adults) starting before or with first dose of antibacterial. Avoid dexamethasone in septic shock, if the patient is immunocompromised, or in meningitis following surgery.

Meningitis caused by meningococci

• Benzylpenicillin or cefotaxime
• Treat for at least 5 days; substitute chloramphenicol if history of anaphylaxis to penicillin or to cephalosporins.
• To eliminate nasopharyngeal carriage give rifampicin for 2 days to patients treated with benzylpenicillin or chloramphenicol.
• Fluid resuscitation may be >100 ml/kg if accompanying meningococcal septicaemia and replacement blood products may be required.

Meningitis caused by pneumococci

• Treat with cefotaxime for 10-14 days; substitute benzylpenicillin if organism is penicillin sensitive; if organism highly penicillin and cephalosporin resistant, add vancomycin and if necessary rifampicin.
• Consider early adjunctive treatment with dexamethasone (but may reduce penetration of vancomycin into cerebrospinal fluid).

Meningitis caused by Haemophilus influenzae

• Treat with cefotaxime for at least 10 days; substitute chloramphenicol if history of anaphylaxis to penicillin or to cephalosporins or if organism resistant to cefotaxime.
• Consider early adjunctive treatment with dexamethasone.
• For H.influenzae type b give rifampicin for 4 days before hospital discharge.

Meningitis caused by Listeria

• Treat for 10-14 days with amoxicillin/ampicillin and gentamicin.

Raised intracranial pressure

• Patients should be considered for corticosteroids, urgent admission to intensive care and elective intubation and ventilation.⁴

Prevention of secondary case of meningococcal meningitis

• Rifampicin 600 mg every 12 hours for 2 days (child 10 mg/kg, or 5 mg/kg if under 1 year) every 12 hours for 2 days.
• Or ciprofloxacin (not licensed for this indication) 500 mg as a single dose (child 5-12 years 250 mg).
• Or IM ceftriaxone (not licensed for this indication but the preferred choice for pregnant women) 250 mg as a single dose (child under 12 years 125 mg).

Prevention of secondary case of Haemophilus influenzae type b disease

Rifampicin 600 mg once daily for 4 days (child 1-3 months 10 mg/kg once daily for 4 days; over 3 months 20 mg/kg once daily for 4 days).

• Immediate: septic shock, including disseminated intravascular coagulation, coma with loss of protective airway reflexes, seizures (30-40% of children, 20-30% of adults), cerebral oedema, septic arthritis, pericardial effusion, and haemolytic anaemia (H.influenzae).
• Subdural effusions: reported in 40% of children aged 1-18 months with bacterial meningitis. Risk factors include young age, rapid onset of illness, low peripheral white cell count and high CSF protein.
• Seizures: occur more commonly during the acute stage of the disease.
• Delayed: decreased hearing or deafness, other cranial nerve dysfunction, multiple seizures, focal paralysis, subdural effusions, hydrocephalus, intellectual deficits, ataxia, blindness, Waterhouse-Friedrichsen syndrome, and peripheral gangrene.

• Prognosis depends on the pathogen, patient's age and condition, and severity of acute illness.
• Patients with severe neurological impairment on presentation or with extremely rapid onset of illness, even if treated immediately, have a 50-90% mortality rate and an even higher rate of morbidity.
• Pneumococcal meningitis has the highest rates of mortality (21%) and morbidity (15%).
• Meningococcal disease has a better prognosis when meningitis accompanies the septicaemia, than when it doesn't.

• Vaccination against Haemophilus type B and Meningitis C.⁴
• Appropriate prophylaxis of people in close contact with those diagnosed.