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Meningitis

NICE guideline [NG240] Meningitis (bacterial) and meningococcal disease: recognition, diagnosis and management. Published: Mar 2024.

NICE BNF Treatment summaries. Central nervous system infections, antibacterial therapy

NICE BNF Treatment summaries. Antibacterials, use for prophylaxis Meningococcal disease: prevention of secondary cases.

NICE guideline [NG33] Tuberculosis 1.3 Active TB. Last updated: Feb 2024.

Meningitis

Meningitis is inflammation of the meninges (made up of the dura, arachnoid and pia mater), the protective membrane layers surrounding the brain and spinal cord. It is most commonly caused by infection, including viral, bacterial, tuberculous and fungal meningitis. Bacterial meningitis and meningococcal disease are medical emergencies requiring urgent hospital assessment and treatment.

This updated UKMLA guide to meningitis is based primarily on NICE NG240, which covers: causes, risk factors, symptoms, complications, diagnosis, and management.

Causes and Risk Factors

Meningitis is most commonly caused by infections:

Cause Organisms Risk factors
Bacterial meningitis Most common organisms in >3 months old
  • Neisseria meningitidis (meningococcus)
  • Streptococcus pneumoniae (pneumococcus)
  • Haemophilus influenzae type b (Hib) – used to be common but now rare due to vaccination

Clarification on terminology:

  • Meningococcal disease = invasive infection caused by Neisseria meningitidis.
  • This term covers both meningococcal meningitis and meningococcal septicaemia.

The following organisms are common in <3 months old

  • Group Streptococcus (GBS)
  • E. coli

Listeria monocytogenes is rare, usually affecting >60 y/o, very young children, those with other risk factors (e.g. pregnancy, cancer, immunosuppression, diabetes, kidney or liver disease, alcohol misuse) [Ref]

Healthcare-associated / post-neurosurgical meningitis (e.g. CSF shunts, EVDs) is associated with: [Ref]

  • Staphylococci (e.g. Staphylococcus epidermidis, Staphylococcus aureus)
  • Gram -ve bacilli (e.g. Pseudomonas aeruginosa, Acinetobacter, E. coli, Klebsiella)

Transmission:

  • Aerosol, droplets, or direct contact with secretions from the upper respiratory tract
  • Transmission usually requires either frequent or prolonged close contact
Young age is the most significant risk factor

Other risk factors:

  • >65 y/o
  • Hyposplenism / asplenism
  • Immunocompromised
  • Incomplete immunisation
  • Leukaemia and lymphoma
  • Liver and kidney disease
  • Student in large shared accommodation (e.g. university)
  • Previous episode of bacterial meningitis or meningococcal disease
  • Cochlear implants
  • Contiguous infection (e.g. otitis media, sinusitis, pneumonia, mastoiditis)
  • Sickle cell disease
Tuberculous meningitis Caused by Mycobacterium tuberculosis

Although tuberculous meningitis is technically a bacterial infection, it is usually discussed separately because it has a different clinical and CSF pattern.

Typical TB risk factors:
  • Close contact with a TB case
  • Born in a high-prevalence area
  • History of untreated / inadequately treated TB infection
  • Immunosuppression
Viral meningitis [Ref]
  • Enterovirus (e.g. Coxsackie A and B viruses, echoviruses) (most common ~85% cases)
  • Parechoviruses
  • Herpes simplex virus
Incidence highest in <3 months old
Fungal meningitis Mostly occur in immunocompromised patients
  • Cryptococcus – most common
  • Candida
  • Histoplasma
Immunocompromised patients

Viral meningitis is the most common and least serious type, due to the widespread use of conjugate vaccines. [Ref1][Ref2]

Bacterial meningitis is rare, but has the most serious complications if unrecognised and untreated.

Non-infective meningitis is less common and is less important for non-specialist level, but may be caused by malignancy, autoimmune/inflammatory disease, or drug-induced aseptic meningitis (e.g. NSAIDs, co-trimoxazole, amoxicillin, ranitidine).

Clinical Features

Key non-specific features:

  • Triad of
    • Fever
    • Neck stiffness (painful limitation of passive neck flexion)
    • Altered mental status
  • Other signs of meningism (apart from neck stiffness)
    • Kernig’s sign (pain or resistance when the knee is passively extended while the hip is flexed at 90°)
    • Brudzinski’s sign (passive neck flexion causes involuntary flexion of the hips and knees)
  • Headache
  • Photophobia
  • Nausea and/or vomiting
  • Seizures

Note that a non-blanching petechial / purpuric rash is NOT a general meningitis feature. It specifically suggests meningococcal disease, especially meningococcal septicaemia (see below for more details).

Meningitis vs encephalitis:

  • Meningitis = inflammation of the meninges
    • Classically causes headache, fever, neck stiffness/meningism and photophobia
    • Consciousness may be normal early, but can become reduced in severe disease
  • Encephalitis = inflammation of the brain parenchyma
    • Classically causes “brain dysfunction” features: altered behaviour, confusion, personality change, seizures, focal neurology or reduced consciousness

Cause-Specific Clinical Patterns

Bacterial meningitis Strongly suspect bacterial meningitis if ALL of the following red flags are present:
  • Fever
  • Headache
  • Neck stiffness
  • Altered level of consciousness or cognition
Meningococcal disease Strongly suspect meningococcal disease if ANY of the following red flags are present:
  • Rapidly progressive and/or spreading non-blanching petechial / purpuric rash
  • Non-blanching rash that is haemorrhagic and >2 mm (purpura)
  • Any symptoms and signs of bacterial meningitis

The most important red flag for meningococcal disease is a non-blanching petechial / purpuric rash.

A non-blanching petechial / purpuric rash is mainly a sign of meningococcal septicaemia, not meningitis itself.

  • A non-blanching petechial or purpuric rash suggests meningococcal septicaemia
  • It may occur with meningococcal meningitis if both meningitis and septicaemia are present
  • However, the absence of a rash does not rule out meningococcal disease
Tuberculous meningitis
  • Usually subacute (>5 days)
  • Typical meningitis features with cranial nerve palsypoor appetite / weight loss
  • Signs of pulmonary TB
  • Associated with typical TB risk factors (see above)
Viral meningitis
  • Often presents with typical meningitis symptoms
  • Less severe than bacterial meningitis
  • May be associated with viral prodrome / systemic viral symptoms
Fungal meningitis
  • Usually gradual onset over weeks to months
  • Seen in immunocompromised patients

Complications

Bacterial meningitis carries the worst prognosis and complications.

Cerebral infarction occurs in 25% of bacterial meningitis cases, which leads to focal neurological deficits

  • Hearing loss (most common ~34%)
  • Seizures
  • Cognitive impairment
  • Motor deficits
  • Visual impairment
  • Speech impairment

Meningococcal septicaemia can lead to more severe complications, including:

  • Shock
  • DIC
  • Skin necrosis / scarring
  • Limb ischaemia / amputation
  • Multi-organ failure

Primary Care / Community Management

Pre-Hospital Management

Top priority:

  • Transfer immediately to the hospital as an emergency
  • Do not perform investigations in primary care

Recommendations regarding antibiotic therapy before transfer:

  • DO NOT delay transfer to hospital to give antibiotics
  • Only if there is likely to be a clinically significant delay in transfer: give IV / IM ceftriaxone or benzylpenicillin outside of hospital

Do not delay transfer to hospital to give antibiotics.

However, pre-hospital antibiotics administration is recommended in the following 2 situations:

  • Strongly suspected meningococcal disease, as long as it does NOT delay transfer to hospital, OR
  • Strongly suspected bacterial meningitis, AND a clinically significant delay in transfer to hospital is likely

Choice of antibiotics:

  • Route: IV / IM
  • Antibiotic: ceftriaxone or benzylpenicillin

For patients with penicillin allergy:

  • If the patient has a severe allergy (e.g. anaphylaxis, angioedema, respiratory distress) → do NOT give antibiotics outside of hospital
  • If the patient has a non-severe allergy → ceftriaxone or benzylpenicillin can be given

The above management pathway specifically applies to suspected bacterial meningitis or meningococcal disease.

However, at initial presentation, bacterial meningitis and meningococcal disease can be difficult to distinguish clinically from other causes of meningitis, such as viral, TB or fungal meningitis. Therefore, patients with suspected meningitis and concerning features should be referred and assessed in hospital to clarify the underlying cause.

Secondary Care Management

Investigation and Diagnosis

Ideally, perform the following tests before starting antibiotics:

  • Bacterial throat swab for meningococcal culture
  • Blood tests
    • Blood culture
    • White blood cell count, CRP
    • Blood glucose (important for CSF analysis)
    • Whole-blood PCR (including meningococcal and pneumococcal)
    • HIV test
  • Lumbar puncture – definitive test (but NOT always performed before antibiotics – see below)

Lumbar Puncture

Lumbar puncture with CSF analysis is the definitive investigation for meningitis and identifying the underlying organism

Step 1: Check for Lumbar Puncture Contraindications

Do not perform lumbar puncture if ANY of the following:

Contraindication Rationale
Infection at lumbar puncture site Passing a needle through infected skin can introduce infection into the CSF
Extensive / rapidly spreading purpura This suggests severe disease like meningococcal septicaemia, DIC.

Performing a lumbar puncture may increase bleeding risk and will delay urgent life-saving treatment.

Risk factors for evolving space-occupying lesion Performing a lumbar puncture in the presence of space-occupying lesion or raised ICP increases the risk of brain herniation
Signs of raised ICP, ANY of the following:
  • Focal neurological features (including seizures or posturing)
  • Abnormal pupillary reactions
  • GCS ≤9, or a progressive and sustained or rapid fall in level of consciousness

Some lumbar puncture contraindications (row 3 and 4 above) overlap with indications to perform neuroimaging (see below for more details).

Step 2: Lumbar Puncture or Not?

Based on the presence or absence of contraindications against a lumbar puncture, there are 2 possible pathways:

No contraindications
  1. Urgent lumbar puncture
  2. Take other microbiology samples (i.e. throat swabs, blood cultures, whole-blood PCR)
  3. Start treatment (empirical antibiotics etc.)
Yes contraindications
  1.  Urgently take other microbiology samples (i.e. throat swabs, blood cultures, whole-blood PCR)
  2. Start treatment (empirical antibiotics etc.)
  3. If lumbar puncture is contraindicated due to risk of space-occupying lesion or raised ICP → neuroimaging (usually CT head) before re-considering lumbar puncture
    • Lumbar puncture is only safe to perform if imaging shows no structural contraindications (e.g. mass effect, midline shift, impending herniation)
    • However, a normal CT does not automatically make lumbar puncture safe, the decision should be made with senior clinical input

Do not routinely perform neuroimaging before lumbar puncture.

Step 3: CSF Analysis (If Lumbar Puncture Performed)

Parameter Bacterial Viral TB Fungal
Opening pressure – / ↑
Appearance Turbid Clear Slightly turbid Clear/turbid
WCC ↑↑ (neutrophils) ↑ (lymphocytes) ↑ (lymphocytes) ↑ (lymphocytes)
Glucose
Protein – / ↑ ↑↑
Gram stain / culture Often +ve Ziehl-Neelsen stain (may be +ve) India ink (may be +ve)

In addition to the parameters listed above, PCR for relevant pathogens should be performed as well.

Management

Bacterial Meningitis

IV antibiotics are the top priority in bacterial meningitis, it should be started ASAP, and within 1 hour of arriving at hospital

Ideally take microbiology samples (esp. blood cultures – this should always be done) and lumbar puncture (not always done – see above) before, then give antibiotics immediately (if safe to do so and will not cause a clinically significant delay to start antibiotics)

Empirical Antibiotic Therapy (Unknown Organisms)

1st line:

  • Ceftriaxone (alternative: cefotaxime)
  • PLUS amoxicillin only if there are risk factors for Listeria monocytogenes (very young children / >60 y/o / pregnancy / immunosuppression / diabetes / alcohol misuse / cancer / kidney or liver disease)

Do not routinely give intravenous aciclovir unless herpes simplex encephalitis is strongly suspected.

Ceftriaxone / cefotaxime can be used as long as there is a non-severe allergy to beta-lactams.

If there is a severe allergy (e.g. anaphylaxis, angioedema, respiratory distress), BNF recommends considering chloramphenicol and seeking specialist advice.

Disclaimer: the exact wording of NICE is to add amoxicillin if there are ‘risk factors for Listeria monocytogenes’, however, these are not specifically defined.

The above-listed risk factors were instead listed in the BNF treatment summary.

Adjunct – Corticosteroid Therapy

IV dexamethasone should also be given with, or before the first dose of antibiotic, if the patient is >3 m/o and bacterial meningitis is strongly suspected or confirmed

Do not give dexamethasone in meningococcal disease

Do not delay antibiotics to wait for dexamethasone to be started

Only continue dexamethasone if meningitis is found to be caused by pneumococcus or Haemophilus influenzae type b

Antibiotic Therapy in Known Organisms

NICE guideline covered the choice of antibiotics for 6 organisms, but there are actually only 2 antibiotic regimens one needs to learn:

  • In terms of the guidelines, there are some discrepancies regarding duration to continue the antibiotic, but the author deems it excessive and is unlikely to be important for exams.
  • Clinically, the choice of antibiotic would be guided by local microbiology guidelines and culture sensitivities
Causative organism 1st line antibiotic 2nd line antibiotic Severe penicillin allergy*
Neisseria meningitidis (including meningococcal disease) Ceftriaxone Cefotaxime Chloramphenicol
Streptococcus pneumoniae
Haemophilus influenzae type b
Group B streptococcus
Enterobacterales (coliforms)
Listeria monocytogenes Amoxicillin / ampicillin Co-trimoxazole Chloramphenicoil + co-trimoxazole
*NICE recommends considering the same penicillin-containing antibiotics if the reaction was not a severe allergy.

Tuberculous Meningitis

TB meningitis requires urgent specialist input.

Standard treatment (12 months in total):

  • Initial 2 months of quadruple therapy (RIPE):
    • Rifampicin
    • Isoniazide (+ pyridoxine / vitamin B6)
    • Pyrazinamide
    • Ethambutol
  • Further 10 months of dual therapy
    • Rifampicin
    • Isoniazide (+ pyridoxine / vitamin B6)

Modify treatment regimen according to drug susceptibility testing

Adjunctive treatment:

  • Give systemic corticosteroid (dexamethasone or prednisolone) – high dose initially and withdraw gradually over 4-8 weeks
  • Consider neurosurgical interventions only if there is raised ICP

Viral Meningitis

Mainstay of management is supportive care (e.g. analgesia, antipyretics, hydration)

  • Most viruses causing meningitis have no specific antiviral treatment
  • Most cases of viral meningitis are self-limiting

Since it is difficult to clinically differentiate viral from bacterial meningitis initially (before lumbar puncture and CSF analysis results are available), empirical antibiotic therapy is usually indicated until bacterial meningitis is definitively excluded. [Ref]

Do not confuse viral meningitis with viral encephalitis.

  • Viral meningitis is usually self-limiting and managed supportively once bacterial meningitis has been excluded.
  • Viral encephalitis is serious and potentially life-threatening. If viral encephalitis is suspected, start empirical IV aciclovir to cover HSV / VZV.

Fungal Meningitis

Fungal meningitis requires urgent specialist microbiology / infectious diseases input and targeted antifungal therapy.

Management of cryptococcal meningitis (most common cause of fungal meningitis): [Ref]

  • Induction with amphotericin Bflucytosine
  • Maintenance with fluconazole

Prevention of Secondary Cases

Bacterial meningitis and meningococcal disease are notifiable diseases.

Antibacterial prophylaxis is aimed at eliminating asymptomatic carriage of Neisseria meningitidis from close contacts of the index case, thereby reducing onward transmission and secondary cases

Indication

Irrespective of vaccination status, the following contacts should be offered antibacterial prophylaxis

  • Contact with the index case in a household-type setting during the 7 days before onset of illness.
  • Sexual or other intimate contact during the 7 days before onset of illness.
  • Direct exposure to large particle droplets or secretions from the respiratory tract

Antibacterial Prophylaxis

  • 1st line: ciprofloxacin
    • Alternative or recent travel to Middle East or Asia: rifampicin
  • Also consider vaccination against Neisseria meningitidis 

References



Related Articles

Encephalitis

Brain Abscess

Disseminated Intravascular Coagulation (DIC)

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