138 - Acute Meningitis Flashcards
What is meningitis?
Acute purulent infection within subarachnoid space, which may involve meninges, SAS and brain parenchyma (meningoencephalitis)
A/w CNS inflammatory reaction - reduced consciousness, seizures, raised ICP, stroke
What are the commonest bacterias for bacterial meningitis? (5)
- Streptococcus pneumoniae (~50%)
- Neisseria meningitis (~25%)
- Group B streptococci (~15%)
- Listeria monocytogenes (~10%)
- Haemophilus influenzae type B (<10%) - significantly reduced due to vaccination
What are the commonest viruses for viral meningitis? (6)
- Enteroviruses (Coxsackie, echovirus)
- VZV
- HSV
- EBV
- Arboviruses (West Nile)
- HIV
What is the commonest pathogen causing meningitis?
What are the risk factors for pneumococcal meningitis? (8)
What is the mortality prognosis with treatment?
Streptococcus pneumoniae
Risk Factors
1. Pneumococcal pneumonia (main risk factor)
2. Acute or chronic pneumococcal sinusitis or OM
3. Alcoholism
4. Diabetes
5. Splenectomy
6. Hypogammaglobulinaemia
7. Complement deficiency
8. Basilar skull fracture - CSF rhinorrhoea
Mortality: 20% despite antibiotics treatment
Why is the incidence of Neisseria meningitidis still > 10% despite vaccine available?
What is the ACIP guideline of vaccination for N. meningiditis?
Routine immunisation 11-18 years old with quadrivalent meningococcal conjugate vaccine (A, C, W, Y) does not contain serogroup B (responsible for 1/3 of cases)
ACIP recommends further vaccination with quadrivalent + serogroup B meningococcal vaccine
- Serogroup B vaccine is poorly immunogenic - does not reduce nasopharyngeal carrriage -> requires quadrivalent for reduction
What are the factors influencing pathogenicity of N. meningitidis and severity of N. meningitidis?
Initiation: often via nasopharyngeal colonisation
Factors: virulence factor, host immune defense
(individuals with complement deficiency highly susceptible)
Can be fulminant - petechial or purpuric rashes
Progressing to death within hours
What are the risk factors for gram negative bacilli meningitis?
- Diabetes
- Cirrhosis and alcoholism
- Recurrent UTI
- Trauma with CSF rhinorrhoea or otorrhoea
Complicates neurosurgical procedures - craniotomy
What are the bacterial meningitis associated with ENT infections? (5)
- Streptococcus
- Gram negative anaerobes
- Staphylococcus aurues
- Haemophilus
- Enterobacteriaceae
What are the bacterial meningitis associated with endocarditis? (5)
- Viridans streptococci
- Staphylococcus aureus
- Streptococcus bovis
- HACEK
- Enterococci
What bacterial meningitis is associated with young (neonates), elderly (>50 years) and immunocompromised? (3)
What are food contaminated with listeria? (4)
- GBS
- Streptococcus agalactiae
- Listeria monocytogenes
Food contaminated with Listeria
Coleslaw
Milk and cheese
Ready-to-eat food - delicatessen meat, hotdogs
Melons (rockmelons)
What are conditions associated with S. aurues and CONS meningitis?
- Invasive neurosurigcal procedures - shunt for hydrocephalus
- Subcutaneous Ommaya reservoirs (IT chemotherapy)
Pathophysiology of bacterial meningitis
- Colonisation and Transportation of Bacteria
- S. pneumoniae, N. meningitidis most common
- Colonises nasopharynx by attaching to epithelial cells
- Transported across in membrane-bound vacuoles or invasion via separations in apical tight junctions -> bloodstream - Polysaccharide capsule -> avoids phagocytosis
- Dissemination
A. Bloodstream -> intraventricular choroid plexus -> infection and access to CSF
B. Adherence of cerebral capillary endothelial cells -> migration into CSF - Rapid multiplication within CSF - absence of host immune defencses (very few WBC, complements, Ig)
- Inflammatory and immune reaction to invading bacteria
–> Responsible for neurologic injury and progression even after CSF has been sterilised by antibiotics
- Bacteria cell wall lysis and components (GNR LPS molecules,
s. pneumoniae teichoic acid, peptidoglycans) induce meningeal inflammation
- Cytokines and chemokines release from immune cells, leukocytosis
- Production of excitatory amino acids, ROS, RNS, mediators incude brain cell death, especially hippocampus dentate gyrus - Action of cytokines and chemokines
- TNF-a and IL-1b increases permeabiltiy of BBB
> Induction of vasogenic oedema, leakage of serum proteins into SAS
- Proteinaceous material exudates and leukocytes obstruct flow of CSF, diminishes resorptive capacity of arachnoid granulations in dural sinuses
> Obstructive and communicating hydrocephalus, concomittant interstitial oedema
- Upregulation of selectins on capillary endothelial cells, leukocytes
> Leukocyte adherence to endothelial cells and migration into CSF
> Increases permeability of blood vessels, further worsening plasma protein leakage into CSF - Neutrophil degranulation
- Toxic metabolites -> cytotoxic oedema, cell death
–> CSF leukocytes do more harm than clearance of bacterial infections - Cerebrovascular dysregulation
- Initial increased blood flow -> reduced due to narrowing of large arteries from enroachment of purulent exudates in SAS, infiltration of aterial wall by inflammatory cells
- Vasculitis and intimal thickening
–> Ischaemia, infarction
> Frequently obstructs/thrombosis in branch of MCA, cerebral venous sinuses, thrombophlebitis of cerebral cortical veins - Raised ICP due to interstitial, vasogenic, cytotoxic oedema
- Coma
- Herniation
- Hydrocephalus
What is the classical triad of meningitis? (3)
- Fever
- Headache
- Nuchal (neck) rigidity
Occurs in >80% of adult cases
What are other features of meningitis apart from classical triad?
- Classical triad (80%) - fever, headache, neck stiffness
- Reduced level of consciousness (75%) - lethargy to coma
- Nausea, vomiting
- Photophobia
- Seizure (15-40%)
> Focal - arterial ischaemia or inarct, CVT, focal oedema
> Generalised - hyponatraemia, cerebral anoxia, toxic effect of antibiotics/antivirals - Raised ICP -> obtundation, coma
(>90% opening pressure > 400mmH2O)
> reduced consciousness, papilloedema, dilated sluggish pupils, CN6 palsy, decerebrate posture - Cerebral herniation (1-8%) - Cushing reflex (bradycardia, hypertension, irregular respiration)
- Special features - meningococcaemia rashes
- Diffuse erythematous maculopapular rash
- Petechial rashes over trunk, lower extremitis, mucous membrane, conjunctiva, palms, soles
Neck stifness is the pathognomonic sign of __, present when neck resists passive __
Kernig’s sign - supine position, thigh and knee flexed on the abdomen, on knee passive __ pain is elicited.
Brudzinski’s sign - supine position, neck passive __ causes spontaneous flexion of hips and knees
** May be false positive in cervical spine disease **
Neck stifness is the pathognomonic sign of meningitis, present when neck resists passive flexion
Kernig’s sign - supine position, thigh and knee flexed on the abdomen, on knee passive extension pain is elicited.
Brudzinski’s sign - supine position, neck passive flexion causes spontaneous flexion of hips and knees
** May be false positive in cervical spine disease **
Lumbar puncture findings in bacterial meningitis:
- Opening pressure
- WBC
- Glucose
- CSF/serum glucose ratio
- Protein
- Gram stain positivity rate
- CSF culture positivity rate
- Latex agglutination or PCR
Opening pressure: > 180mmH2O
WBC: 10-10,000/uL, neutrophils predominant
RBC: absent
Glucose: < 2.2 mmol/L (< 40mg/dL)
CSF/serum glucose ratio: low < 0.6, highly suggestive if < 0.4
Protein: > 0.45g/L (> 45mg/dL)
Gram stain: positive in > 60%
CSF culture: positive in > 80%
Latex agglutination test or PCR: S. pneumoniae, N. meningitidis, E. coli, L. monocytogenes, H. influenzae, S. agalactiae, viruses
Will antibiotics initiation prior to LP affect CSF result?
No - CSF WBC, glucose concentration, organisms, PCR will likely remained similar and investigative
Will hypoglycaemia protocol treatment with 50mL D50% affect CSF glucose concentration?
No - it takes at least 30 minutes to several hours for CSF glucose to reach equilibrium with blood glucose
Poor prognosis indicators (8)
- Reduced consciousness on admission
- Onset of seizure within 24 hours of admission
- Signs of increased ICP
- Age - young (infants) and > 50 years old
- Severity - shock, mechanical ventilation
- Delayed treatment initiation
- Reduced CSF glucose < 2.2mmol
- Marked increased CSF protein (> 3g/L)
What are the sequelae of meningitis? (7)
Incidence of sequelae in ___ survivors
Incidence of sequelae ~25% survivors
Sequelae:
1. Intellectual function disability
2. Memory impairment
3. Seizure and epilepsy
4. Sensorineural hearing loss
5. Chronic dizziness
6. Gait disturbance, ataxia
7. Hemiparesis, hemianopia, CN palsy
Empirical treatment for meningitis and rationality
Combination: 3rd/4th gen cephalopsporin + acyclovir
- Ceftriaxone 2g Q12H
- S. pneumoniae, GBS, H. influenzae, N. meningitidis - Acyclovir 800mg Q8H
- HSV
—————– - Add on ampicillin in:
- L. monocytogenes in < 3months or > 55 years
- Impaired cell mediated immunity: chronic illness, transplant, pregnancy, malignancy, immunosuppressed - Add on metronidazole in:
- Gram negative anaerobes in otitis, sinusitis, mastoiditis
—————- - Hospital acquired bacterial meningitis
> vancomycin + ceftazidime or meropenem
- MRSA, P. aeruginosa
What are the possible adverse effect of cephalosporins, especially cefepime, in treatment of meningitis?
Seizures
Myoclonus
Encephalopathy
Definitive treatment for N. meningitidis meningitis
- Antibiotics, duration, chemoprophylaxis for close contact
A. Antibiotics
- Penicillin sensitive: penicillin G or ampicillin
- Penicillin resistance: ceftriaxone (or cefotaxime)
B. Duration: 7 days
C. Chemoprophylaxis
- Rifampin 600mg Q12H for 2 days (adult) or 10mg/kg Q12H for 2 days in children > 1 years
(Not recommended in pregnant women)
- Others: PO azithromycin 500mg once dose
- Others: IM ceftriaxone 250mg once dose
Close contacts: oropharyngeal secretions - kissing, sharing toys, beverages, cigarettes
What is the normal composition of CSF?
- Opening pressure, WBC, RBC, glucose, protein
Opening pressure: 8-15mmHg or 100-180mmH2O
WBC: 0-5/mm3
RBC: 0/mm3
Glucose: 2.5 - 4.4mmol/L (45-80mg/dL)
Protein: 15-45mg/dL
What are the common contraindications to LP? (6)
- Localised skin infection: cellulitis, abscess
- Space-occupying lesion
- Herniation - uncal, central, transtentorial, cerebellar
- Coagulopathy - thrombocytopenia, liver failure
- Anticoagulant use
- Patient refusal
Role of adjunctive corticosteroids in treatment of bacterial meningitis
Dose: IV dexamethasone 4mg Q6H for 4 days
Indication: streptococcus pneumoniae bacterial meningitis
- If CSF culture not S. pneumoniae, can be discontinued
Mechanism of action:
- Reduces ICP, brain oedema and meningeal inflammation
- Reduces inciidence of sensorineural hearing loss
- Significant reduction in unfavourable outcome and mortality
