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Introduction & Definition
What is meningitis?
  • Meningitis describes an inflammatory process involving the pia matter, arachnoid and adjacent cerebrospinal fluid
  • It is a common condition with a broad differential diagnosis

What is aseptic meningitis?

  • Defined as the presence of meningeal inflammation without signs of bacterial growth in cultures
  • Usually due to viral infection but may be due to fungal infection or other non-infectious causes

What is the distinction between acute versus chronic meningitis?

Two different syndromes that have very distinct causes:

Acute Meningitis
Syndrome of fever, neck stiffness, and altered mental status with an onset of hours to days, often with rapid progression
Chronic Meningitis
Syndrome of symptoms and abnormal cerebrospinal fluid (CSF) that persists for four weeks or more

Epidemiology, Clinical Course & Prognosis

How common is meningitis?

  • Annual incidence of all-cause meningitis in UK adults reported as 13·47 per 100 000
    • Confirmed viral meningitis has an annual incidence of 2.73 per 100,000
      • Enteroviruses accounted for over 50% of confirmed cases
    • Confirmed viral meningitis has an annual incidence of 1.24 per 100,000.
    • Remaining cases due to other causes or had no identifiable organism,
  • Incidence in European countries likely to have decreased significantly in recent decades due to the impact of vaccination programmes

What are the prognosis and outcomes reported in meningitis?

  • Bacterial meningitis shown to carry significant morbidity and mortality:
    • Mortality varies with causative organism:
      • Meningococcal sepsis – up to 57%
      • Meningococcal meningitis without sepsis – 7%
      • Pneumococcal meningitis – 30%
    • Outcome particularly poor if fulminant presentation (presenting with coma within 24–48 h of hospitalisation):
      • Overall mortality is 41%
      • Of those surviving, only 20% were discharged with good to full recovery (Modified Rankin scale 0-2)
    • Morbidity common in bacterial meningitis:
      • Up to 50% of cases may have subsequent focal neurological deficits
      • Commonest is hearing impairment – 14%
  • Viral meningitis carries a better prognosis, though data on long-term outcomes limited
    • Large study showed no mortality associated with viral meningitis
    • Up to one-third may have long-term neurological sequelae


How do pathogens gain entry to the skull in meningitis?

  • In most cases, the infection causing meningitis arises in the nasopharynx:
    • Can lead to intravascular invasion and bacteraemia
    • Meningeal invasion occurs at high-level bacteraemia following penetration of the blood-brain barrier
    • Bacteria associated with meningitis express antiphagocytic capsular polysaccharide that enables survival/multiplication within the blood
  • Direct (non-haematogenous) spread from contiguous structures less common
    • May occur in fractures, sinusitis or post-surgery

What are the pathophysiological changes that occur in meningitis?

Aetiology & Risk Factors

What are the most common aetiologies of meningitis in adults?

  • In a recent study of meningitis in adults (meningitis symptoms and CSF leucocyte count >4×106 cells/L) in the UK, aetiology was found to be:
    • Bacterial: 16%
    • Viral: 36%
    • Other: 6%
    • Unknown: 42%

What are the bacteria commonly responsible for bacterial meningitis?

Causative bacteria for meningitis varies according to age:

  • Streptococcus agalactiae (Group B)
  • Gram –ve bacilli (e.g. E. coli, Klebsiella, Haemophilus influenzae)
  • Listeria Monocytogenes
Children 1-24 months
  • Neisseria Meningitidis
  • Streptococcus pneumonia
  • Streptococcus agalactiae (Group B)
  • Haemophilus influenza
Older Children & Younger Adults
  • Neisseria Meningitidis (22%)
  • Streptococcus pneumonia (18%)
  • Staphylococcus Aureus (10%)
Older Adults
  • As for younger adults
  • Listeria Monocytogenes
  • Aerobic gram-negative bacilli
  • Significant change in aetiology has occurred over recent years due to UK vaccination programmes:
  • Incidence of Haemophilus influenzae Type b, serogroup C meningococcus and pneumococcal disease is reducing
  • Serogroup B meningococcus is the most common cause in children aged three months or older as there is currently no vaccine available

What is aseptic meningitis?

  • Defined as the presence of meningeal inflammation without signs of bacterial growth in cultures
  • Usually due to viral infection but may be due to fungal infection or other non-infectious causes

What are the common causes of aseptic meningitis?

  • Viruses
  • Mycobacterium
  • Syphilis
  • Cryptococcus
  • Listeria
  • Brucella
  • Mycoplasma
  • Neurocysticercosis
  • Toxoplasmosis
  • Leptospirosis
  • Autoimmune disease
  • Carcinomatous meningitis
  • Parameninges infection
  • Drug-induced meningitis

What are the viruses commonly responsible for aseptic meningitis?

  • Enterovirus
  • Coxsackie virus A&B
  • Echovirus
  • Arbovirus
  • HIV
  • HSV-2
Less Frequent
  • LCV
  • Mumps
  • Adenovirus
  • CMV
  • EBV
  • Influenza A&B
  • Measles
  • Parainfluenza
  • Rubella
  • VZV
  • HHV-6


What are the clinical features of meningitis?

  • Classical presentation is with a triad of fever, altered mental state and neck stiffness
  • Other presenting features include:
Features of Systemic Infection
  • Fever
  • Nausea
  • Malaise
  • High fever
  • Purpuric or petechial skin rash (in meningococcal meningitis)
  • Neck stiffness
  • Headache
  • Photophobia
CNS dysfunction
  • Agitation
  • Decreased consciousness
  • Seizures
  • Focal neurological defect

How commonly are characteristic clinical features seen in bacterial meningitis?

  • Frequency of clinical features was reported in a large Dutch trial of 696 patients
  • Importantly, classical clinical signs may be absent, and diagnosis should not be excluded solely on the absence of classic clinical features
Nausea & vomiting
Neck stiffness
Fever (>38°c)
Altered mental state
Focal neurological deficit
Triad of fever, neck stiffness and altered mental state

What unique presenting features are linked to meningitis of differing aetiologies?

Common Patient Groups
Notable Clinical Features
Notable CSF Features
Listeria monocytogenes
  • Elderly
  • Immunocompromised
  • Pregnant
  • Diarrhoea is a common symptom
  • Meningitis may have a more insidious onset
  • May present with focal seizures
  • Neutrophilic (polymorphonuclear) pleocytosis (>500 cells/mm3)
  • High protein (>1.0 g/L) and low serum to CSF glucose ratio (<0.4)
  • Characteristic organism in wet mounts of CSF showing flagellar-driven 'tumbling' motility
  • Gram stain positive in 25-30%
Streptococcus pneumoniae
  • Immunocompromised
  • Splenectomy
  • S pneumoniae endocarditis, otitis or pneumonia
  • Non-specific features of bacterial meningitis
  • Classic diagnostic triad may be absent in up to half of patients
  • May have focus of infection from ear, sinuses or lungs
  • Neutrophilic (polymorphonuclear) pleocytosis (>500 cells/mm3)
  • High protein (>1.0 g/L) and low serum to CSF glucose ratio (<0.4)
  • Gram stain positive in 90% of cases
  • Culture positive in 75% of cases
Neisseria meningiditis
  • Infants, children, and young adults
  • Epidemics in subgroups such as military personnel or students in dormitories
  • More rapid clinical progression than any other acute form of bacterial meningitis - adults become seriously ill within hours
  • May be preceded by respiratory illness or a sore throat
  • Petechial skin rashes occur in about half of all individuals
  • Shock, circulatory collapse and disseminated intravascular coagulation (DIC) may occur
  • Neutrophilic (polymorphonuclear) pleocytosis (>500 cells/mm3)
  • High protein (>1.0 g/L) and low serum to CSF glucose ratio (<0.4)
  • Gram stain positive in 70-90% of cases
  • Culture positive in 40-60% of cases
  • Infants, children, and young adults
  • Infants, children, and young adults
  • Features of meningism (neck stiffness, headache and photophobia)
  • Fever is not always present
  • Other non-specific symptoms such as diarrhoea, vomiting, muscle pain, and sore throat are sometimes seen
  • Patients with HSV-2 meningitis rarely have concur- rent genital ulcers caused by the virus
  • VZV meningitis can occur with or without the rash of chickenpox or shingles
  • There is usually no reduced conscious level in adults with viral meningitis.
  • 'Gin' Clear appearance
  • Lymphocytic (mononuclear) pleocytosis (<1000 cells/mm3)
  • Normal-high protein (0.5-1.0 g/L) and normal serum to CSF glucose ratio (<0.6)
  • PCR ≥90% sensitivity
  • May be initially normal with negative PCR in about 5-10% of adults – repeat in 24-48 hours before the excluding diagnosis of strong suspicion
  • HIV infection
  • Immunocompromised
  • Solid organ transplantation
  • Malignancy
  • Sarcoidosis
  • Cirrhosis
  • Variable presentation ranging from several days to 8 months
  • Typically insidious onset over 2-week
  • Cranial neuropathies may be present.
  • Cough, dyspnoea, and skin rash suggest disseminated disease
  • Lymphocytic (mononuclear) pleocytosis (100-500 cells/mm3)
  • Classically very high protein (1.0-5.0g/L) and very low serum to CSF glucose ratio (<0.4)
  • Increase in opening pressure (median of 24 cm H2O)
  • Cryptococcal antigen has a sensitivity of 94-98%
  • Culture has a sensitivity of 72%
  • Coming from endemic area
  • HIV infection
  • Immunocompromised
  • Children ages 2–4
  • Malnutrition
  • Variable presentation ranging from a rapidly progressive meningitis syndrome to slowly progressive dementia.
  • Prodromal phase of low-grade fever, malaise, headache, and personality changes can be seen
  • Altered mental status and cranial neuropathies are common
  • Seizures are uncommon
  • Lymphocytic (mononuclear) pleocytosis, though polymorphonuclear or mixed pleocytosis, does not exclude a diagnosis (100-500 cells/mm3)
  • Appearance often described as showing a fibrin web
  • Classically very high protein (1.0-5.0 g/L) and very low serum to CSF glucose ratio (<0.4)
  • Acid-fast staining is <20% sensitive
  • Cultures are positive in up to 60% but may take up to 6 weeks, often too late to aid in clinical decision making

What are the complications of bacterial meningitis in adults?

  • Focal neurologic deficits (37%)
  • Seizures (17%)
  • Hydrocephalus (5%)
  • Ischaemic stroke (25%)
  • Haemorrhagic stroke (3%)
  • Subdural empyema (2%)
  • Sinus thrombosis (1%)
  • Deafness (20%)
  • Cerebral venous sinus thrombosis
  • Intellectual deficit
  • Death (15-20%)
  • Cardiorespiratory failure (30%)
  • Severe sepsis
  • Peripheral ischaemia and gangrene
  • Syndrome of Inappropriate ADH secretion
  • Waterhouse-Friderichsen syndrome (Adrenal gland failure)
Work-Up Summary

How do you work up the patient with suspected meningitis?

To Determine Diagnosis
  • Consider need for CT prior to lumbar puncture:
    • Perform to exclude mass lesion if altered consciousness, focal signs, papilledema, a recent seizure or is immunocompromised
    • Do not delay treatment for CT – take blood cultures and commence antibiotics before scanning
  • Lumbar puncture & CSF examination (if mass lesion excluded):
    • Opening pressure
    • Glucose, protein, lactate
    • Cell count
    • Gram stain
    • Bacterial culture
    • Pneumococcal and meningococcal PCR
    • Viral PCR (enteroviruses, herpes simplex viruses type 1 and 2 (HSV-1 and HSV-2) and varicella zoster virus (VZV)
  • Blood investigations:
    • Blood cultures
    • Pneumococcal and meningococcal PCR
    • Glucose
    • Lactate
    • Procalcitonin
    • Full blood count, urea, creatinine, electrolytes, liver function tests and clotting screen
    • Additional investigations to determine aetiology:
  • Throat swab for meningococcal culture
  • Stool and/or throat swabs should be tested for enterovirus by PCR
  • Selected investigations to detect source of infection:
    • Chest X-ray – pneumonia
    • Skull X-ray – fracture
    • Sinus X-ray – sinusitis
    • Petrous views – mastoiditis
To Assess for Complications
  • Assess serum electrolytes (high frequency of SIADH)

Laboratory Investigations

What are the characteristic CSF findings in the different types of meningitis?

Bacterial Meningitis
Viral Meningitis
TB Meningitis
Fungal Meningitis
Opening Pressure
Normal or slightly raised
'Gin' Clear
Fibrin web
Fibrin web
Cell Differential
Neutrophilic (polymorphonuclear) pleocytosis
Lymphocytic (mononuclear) pleocytosis
Lymphocytic (mononuclear) pleocytosis
Lymphocytic (mononuclear) pleocytosis
WCC (per mm3)
(Up to 100,000)
Protein (g/L)
Normal - high
High - very high
Glucose-Serum Ratio

(2.5-3.5 mmol/L)

Low normal
Very Low
Microscopic stain
25-90% positive
Gram Stain
6-10% positive
ZN Stain
50% positive
India Ink Stain (cryptococcus)
60-90% positive
Viral culture rarely positive (<5%)
60-70% positive
80-90% positive
HSV ≥90% positive
60-90% positive
Antigen 95% positive

What are the sensitivities and specificities of laboratory investigations for meningitis?

CSF Staining
CSF Staining
CSF Staining
Gram Stain (Bacteria)

(Less likely if antibiotics given before LP)


L. monocytogenes

25 – 35%

H. influenzae


N meningitides


S. pneumoniae

India Ink Stain (Fungi)
Ziehl–Neelsen Stain (Tuberculosis)
CSF Culture
CSF Culture
CSF Culture
Bacterial Culture

(If collected before antibiotics started)

Tuberculosis Culture
Fungal culture
Antigen Testing
Antigen Testing
Antigen Testing
S. pneumoniae antigen
Cryptococcal antigen
Viruses (HSV, VZV and mumps)

(In about 5-10% of adults with proven HSV encephalitis, initial CSF PCR negative. If the still suspected, a second CSF examination after 24-48 hours should be undertaken before the diagnosis can be safely excluded)

Bacteria (S. pneumoniae, N. meningitidis)
TB (GeneExpert)
Blood Cultures
Blood Cultures
Blood Cultures
H. influenzae
N meningitides
S. pneumoniae
Imaging Investigations

What is the role of CT imaging in meningitis?

  • Exclude contraindications to lumbar puncture
  • Aid in diagnosis of meningitis or identification of other causative pathologies
  • Evaluate for conditions predisposing to meningitis (skull fracture, sinus or mastoid infection, congenital anomalies)
  • Identify and monitor complications of meningitis (hydrocephalus, subdural effusion, empyema, and infarction and exclude parenchymal abscess and ventriculitis)

When should a CT scan be performed before LP in meningitis?

  • CT imaging is important when raised ICP suspected:
    • Lumbar puncture may precipitate cerebral herniation
  • Should be performed if in all patients presenting with:
    • Focal neurologic deficits (excluding cranial nerve palsies)
    • New-onset seizures
    • Severely altered mental status (Glasgow Coma Scale score <10)
    • Severely immunocompromised state
  • In patients lacking these characteristics, CT imaging is not recommended before lumbar puncture

What are the findings of meningitis on a CT scan?

  • Frequently normal
  • Signs of meningitis include:
    • Subtle hydrocephalus 
    • Hyperdensity around basal cisterns
    • Leptomeningeal enhancement (enhancement of the brain surface)
  • Complications or sources of infection are often seen

How frequently are complications or sources of sepsis identified on CT head?

  • Abnormalities requiring further intervention are frequently found on CT head
  • In a study of 299 patients with meningitis, the frequency of abnormalities identified were:
At Admission
At Any Point During Clinical Course
Brain Infarction
Sinusitis or Otitis
Cerebral Oedema
Empyema or Abscess
Intracranial Haemorrhage
Other Abnormality
Management Summary
How do you manage a patient with meningitis?
Resuscitation & Supportive Management
  • Ensure appropriate staff available to manage patient
  • ABC approach treating abnormalities as found:
  • Consider need for intubation for airway protection:
    • Strongly consider if GCS <12
  • Maintain adequate blood pressure aiming MAP {{gt}65mmHg:
    • Ensure euvolemia with crystalloids as first-line fluid
    • Noradrenaline or vasopressin first-line vasopressor agents
    • Albumin replacement fluid and hydrocortisone 200mg should be considered if hypotensive shock despite initial corrective measures
  • Treat suspected or proven seizures early:
    • EEG monitoring useful in suspected or proven seizures or those with fluctuant GCS
  • Treat suspected or proven raised intracranial pressure:
    • Ensure basic (tier 1) therapy is instigated to control ICP and maintain cerebral perfusion
    • Routine monitoring of ICP not routinely recommended
  • Manage bleeding and overt DIC
Specific Management
  • Ensure antibiotics given immediately:
    • Should be given within 1 hour of diagnosis
    • Don't wait for identification of organism or delay for CT/LP
    • Aim to take blood cultures before administration
  • Treat with appropriate empiric antibiotic therapy initially:
    • Neonates (<1 month):
      • Cefotaxime plus amoxicillin/ampicillin/penicillin
    • Children 1month-18 years:
      • Cefotaxime or ceftriaxone
      • If suspected resistance to penicillin (recently travelled to at risk country), add vancomycin or rifampicin
    • Adults:
      • Cefotaxime 2 g 6 hourly or ceftriaxone 2 g 12 hourly
      • If >60, add amoxicillin 2g 4 hourly in those >60 to cover listeria
      • If suspected resistance to penicillin (recently travelled to at risk country), add vancomycin or rifampicin
  • Target antibiotic therapy subsequently if organisms isolated
  • Commence steroid therapy in suspected bacterial meningitis:
    • 10 mg dexamethasone IV 6 hourly
    • Commence on admission, either shortly before or simultaneously with antibiotics
    • If pneumococcal meningitis is confirmed or probable, continue for 4 days
  • If viral meningitis is suspected, aciclovir or valaciclovir may be beneficial
Referral & Deposition
  • Consider critical care admission if:
    • Evidence of meningococcal sepsis
    • Cardiovascular instability
    • Frequent seizures
    • Altered mental status
  • Notify relevant public health authority of all suspected cases regardless of aetiology:
    • Acute meningitis is a notifiable disease in the UK
Antimicrobial Therapy

What are the recommended empirical antibiotics for meningitis?

  • Antibiotics must penetrate CSF and be given in an appropriate bactericidal dosage
  • Recommended empirical therapy is based upon age given potential causative organisms
No Penicillin Allergy
Penicillin Allergy
Adults <60 years of age
Cefotaxime 2 g 6 hourly
Ceftriaxone 2 g 12 hourly
Chloramphenicol 25 mg/kg 6 hourly
Adults ≥60 years of age
Cefotaxime 2 g 6 hourly
Ceftriaxone 2 g 12 hourly
Amoxicillin 2 g 4 hourly
Chloramphenicol 25 mg/kg 6 hourly
Co-trimoxazole 10-20 mg/kg (of the trimethoprim component) in four divided dose
  • IV Vancomycin (15-20 mg/kg bd) or Rifampicin (600 mg bd) should be added if penicillin resistance is suspected (e.g. patient has recently arrived from a country with high rates of resistance)

Which antibiotics are recommended for specific identified pathogens in meningitis?

  • If causative organism identified, appropriate targeted therapy should be used:
No Penicillin Allergy
Penicillin Allergy
Streptococcus pneumoniae

If sensitive to penicillin:

Cefotaxime 2 g 6 hourly
Ceftriaxone 2 g 12 hourly

If non-susceptible to penicillin:

Cefotaxime 2 g 6 hourly
Ceftriaxone 2 g 12 hourly
Vancomycin 5-20 mg/kg 12 hourly
Rifampicin 600 mg bd

Chloramphenicol 25 mg/kg 6 hourly
Neisseria meningitidis
Cefotaxime 2 g 6 hourly
Ceftriaxone 2 g 12 hourly
Chloramphenicol 25 mg/kg 6 hourly
Co-trimoxazole 10-20 mg/kg (of the trimethoprim component) in four divided dose
Listeria monocytogenes
Amoxicillin 2g 4 hourly
Co-trimoxazole 10-20 mg/kg in 4 divided doses
Haemophilus influenza
Cefotaxime 2 g 6 hourly
Ceftriaxone 2 g 12 hourly
Moxifloxacin 400 mg OD
Benzylpenicillin 2.4 g 4 hourly
When should antibiotics be commenced for meningitis?
  • Antibiotic therapy should start as soon as possible in suspected bacterial meningitis (within 1 hour of diagnosis:
    • Delayed administration is strongly associated with death and poor outcome in meningitis
    • Should not be delayed for lumbar puncture or imaging investigations if clinical suspicion
  • Blood cultures must be drawn before initiating antibiotics to increase the chance of identifying the causative pathogen

How long should antibiotics be continued for in bacterial meningitis?

  • Recommended duration of antibiotic therapy depends upon which pathogen is identified.
    • Streptococcus pneumoniae – 10 days if stable (14 days if slow responder or resistant organism)
    • Neisseria meningitides – 5 days
    • Listeria monocytogenes – 21 days
    • Haemophilus influenza – 10 days
  • If no pathogen is identified, antibiotics can be stopped after 10 days
  • Treatment duration may need to be extended if patient is not responding

Steroid Therapy

What are the benefits of steroid therapy in acute meningitis?

  • May reduce mortality though only with certain causative organisms:
    • Significant reduction in death seen in patients with streptococcus pneumoniae meningitis (29.9% versus 36.0%),
    • Not significantly reduced in all-cause meningitis (17.8% versus 19.9%)
  • May improve long-term outcome in survivors:
    • Significantly reduction in hearing loss (13.8% versus 19.0%)
    • Significantly reduction in neurological sequelae (17.9% versus 21.6%).
How and when should steroids be administered in bacterial meningitis?
  • All adults suspected of having bacterial meningitis should receive steroids
    • Should be given before or with the administration of antibiotics 
    • May still be beneficial if initiated up to 12 h after first dose of antibiotics
  • Recommended therapy is 10 mg dexamethasone IV 6 hourly
  • Recommended duration depends upon organism identified:
    • Continue for 4 days in confirmed or suspected pneumococcal meningitis
    • If another cause of meningitis is confirmed or thought probable, steroids should be stopped
Critical Care Admission & Referral

Which patients with meningitis should be admitted to critical care?

  • Intensive care teams should be involved early in patients, given the high mortality rate and predisposition to rapid deterioration 
  • Suggested criteria for intensive care admission include:
    • Rapidly evolving rash
    • GCS <12 or less or a drop of >2 points (Intubation should be strongly considered in those with a GCS <12)
    • Requiring monitoring or specific organ support
    • Uncontrolled seizures
    • Evidence of severe sepsis

Postexposure Prophylaxis

In the setting of documented bacterial meningitis, who should receive postexposure prophylaxis?

  • Goal of postexposure prophylaxis is to eradicate nasopharyngeal carriage
  • There are two pathogens for which one would consider postexposure prophylaxis with specific indications listed as follows:
Individuals Requiring Prophylaxis
Prophylactic Options
N. meningitidis
  • Extended period of contact (>8 hours) in close proximity (within 3 feet)
  • Contact with oral secretions, with such as activities as kissing, mouth-to-mouth resuscitation, intubation
  • Household contacts, including communal living (military recruits, college dormitory residents)
Ciprofloxacin 500mg PO
Rifampin10mg/kg PO every 12 hours for 2 days
Ceftriaxone 250mg IM
H. influenzae
  • For children younger than 4 years of age, prophylaxis is suggested for all household contacts, including adults
  • Prophylaxis of day-care contacts can be considered if applicable
Rifampin 20 mg/kg per day for 4 days

Which cases of meningitis should be reported to prevent secondary cases?

  • Meningitis and meningococcal sepsis are notifiable diseases in the UK:
    • All cases of meningitis (regardless of aetiology) should be notified to the relevant public health authority
    • Forms a legal obligation to ensure the relevant authority is aware
  • Prophylaxis of contacts is initiated by the Consultant in health protection and not the admitting clinicians


The Guidewire
Trainee in ICM & Anaesthesia


The Guidewire
Trainee in ICM & Anaesthesia