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Question No. 2
Q: What are the clinical features of meningitis?
Answer No. 2
- 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)
Meningism
- Neck stiffness
- Headache
- Photophobia
CNS dysfunction
- Agitation
- Decreased consciousness
- Seizures
- Focal neurological defect
Question No. 3
Q: What are the bacteria commonly responsible for bacterial meningitis?
Answer No. 3
Causative bacteria for meningitis varies according to age:
Neonates
- 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
Question No. 4
Q: What is aseptic meningitis?
Answer No. 4
- 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
Question No. 5
Q: What are the common causes of aseptic meningitis?
Answer No. 5
Infectious
Non-Infectious
- Viruses
- Mycobacterium
- Syphilis
- Cryptococcus
- Listeria
- Brucella
- Mycoplasma
- Neurocysticercosis
- Toxoplasmosis
- Leptospirosis
- Autoimmune disease
- Carcinomatous meningitis
- Parameninges infection
- Drug-induced meningitis
Question No. 6
Q: What are the viruses commonly responsible for aseptic meningitis?
Answer No. 6
Common
- Enterovirus
- Coxsackie virus A&B
- Echovirus
- Arbovirus
- HIV
- HSV-2
Less Frequent
- LCV
- Mumps
Rare
- Adenovirus
- CMV
- EBV
- Influenza A&B
- Measles
- Parainfluenza
- Rubella
- VZV
- HHV-6
Question No. 7
Q: How do pathogens gain entry to the cranium in meningitis?
Answer No. 7
- 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
Question No. 8
Q: What are the pathophysiological changes that occur in meningitis?
Answer No. 8
Question No. 10
Q: How would you investigate this patient for suspected meningitis?
Answer No. 10
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)
Question No. 11
Q: What is the role of CT in meningitis?
Answer No. 11
- 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)
Question No. 12
Q: When should CT scan be performed before LP in meningitis?
Answer No. 12
- 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
Question No. 13
Q: What are the characteristic CSF findings in bacterial meningitis?
Answer No. 13
Normal
Bacterial Meningitis
Opening Pressure
5-20
>30
Appearance
Normal
Turbid
Cell Differential
Normal
Neutrophilic (polymorphonuclear) pleocytosis
WCC (per mm3)
<3
>500
(Up to 100,000)
(Up to 100,000)
Protein (g/L)
0.2-0.4
>1
High
High
Glucose-Serum Ratio
0.5-0.66
(2.5-3.5 mmol/L)
<0.4
Low
Low
Lactate
Normal
Elevated
Gram stain
Normal
25-90% positive
Gram Stain
Gram Stain
Microscopy & culture
-
60-90% positive
PCR
-
-
Other
-
-
Question No. 14
Q: Which patients with meningitis should be admitted to critical care?
Answer No. 14
- 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
Question No. 15
Q: What are the complications of bacterial meningitis that could occur in a patient admitted to the critical care unit with meningitis?
Answer No. 15
Neurological
- 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
Systemic
- Death (15-20%)
- Cardiorespiratory failure (30%)
- Severe sepsis
- Peripheral ischaemia and gangrene
- Syndrome of Inappropriate ADH secretion
- Waterhouse-Friderichsen syndrome (Adrenal gland failure)
Question No. 16
Q: How would you manage a patient admitted to your unit with suspected meningitis?
Answer No. 16
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
- Neonates (<1 month):
- 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
Question No. 17
Q: What are the recommended empirical antibiotic regimens for a patient with suspected bacterial meningitis?
Answer No. 17
- 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
OR
Ceftriaxone 2 g 12 hourly
OR
Ceftriaxone 2 g 12 hourly
Chloramphenicol 25 mg/kg 6 hourly
Adults ≥60 years of age
Cefotaxime 2 g 6 hourly
OR
Ceftriaxone 2 g 12 hourly
AND
Amoxicillin 2 g 4 hourly
OR
Ceftriaxone 2 g 12 hourly
AND
Amoxicillin 2 g 4 hourly
Chloramphenicol 25 mg/kg 6 hourly
AND
Co-trimoxazole 10-20 mg/kg (of the trimethoprim component) in four divided dose
AND
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)
Question No. 18
Q: When should antibiotics be commenced for meningitis?
Answer No. 18
- 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
Question No. 19
Q: How long should antibiotics be continued for in bacterial meningitis?
Answer No. 19
- 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
Question No. 20
Q: What are the benefits of steroid therapy in acute meningitis?
Answer No. 20
- 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%).
Question No. 21
Q: How and when should steroids be administered in bacterial meningitis?
Answer No. 21
- 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
Question No. 22
Q: What preventative measures should be taken when a patient with meningococcal meningitis is admitted?
Answer No. 22
- 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 should initiated by the Consultant in health protection to eradicate nasopharyngeal carriage in those with a certain level of contact to the patient
Pathogen
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
OR
Rifampin10mg/kg PO every 12 hours for 2 days
OR
Ceftriaxone 250mg IM
OR
Rifampin10mg/kg PO every 12 hours for 2 days
OR
Ceftriaxone 250mg IM