L15 - Infections of the CNS (Meningitis & Brain Abscess) Flashcards
Define Meningitis
Inflammation of the meninges
What are the four possible routes of infection by which meningitis might arise?
Blood-borne
Paraminingeal suppuration
Direct spread through dural defect
Direct spread through cribriform plate
Give several examples of the possible complications of meningitis
Death Subdural collection Cerebral vein thrombosis Hydrocephalus 9-15% Deafness (Hib) Convulsions Visual/Motor/Sensory deficit
What are the five causative organisms most commonly implicated in meningitis?
Neisseria meningitidis Streptococcus pneumoniae Haemophilius influenzae type B Escherichia coli Listeria monocytogenes
In what group is N. meningitidis most common?
Children
Young adults
In what groups is S. pneumoniae most common?
Elderly
Children <2yrs
In what group is H. influenzae type B most common?
Children <5yrs
In what group is E. coli most common?
Neonates
In what group is L. monocytogenes most common?
Neonates
Immunocompromised
Describe the characteristics of normal cerebrospinal fluid
Low protein
Low IgG
No lymphatics
BBB so only lipophilic compounds
What bacterial factors act as inflammatory mediators?
Endotoxins of Gram-ve bacteria
Lipoteichoic peptidoglycan components of Gram+ve cell walls
TNF, IL-1/6/8, NO, PAF
What immune cells migrate to the CSF following the effect of these inflammatory mediators?
Neutrophils
What effect does the migration of neutrophils to the CSF have?
Release of proteolytic products (Ox radicals)
What effect do Ox radicals have?
They damage the vascular endothelium
Changes BBB permeability
Alters CSF dynamics
Describe the pathogenesis of bacterial meningitis
Nasopharynx to
Bloodstream to
Choroid Plexus to
CSF
What is the most common route of infection?
Blood-borne from a respiratory site (nasopharynx)
Across the choroid plexus into the subarachnoid space and into the CSF
Which three organisms can easily colonise the nasopharynx and penetrate vascular tight junctions?
S. pneumoniae
N. meningitidis
H. influenzae type B
What bacterial factors enable colonisation of the nasopharynx?
IgA protease
Pili
What bacterial factors enable bacteraemia?
Endocytosis across tight junctions
Capsules to resist lysis/phagocytosis
What factors cause the slow immune response in the subarachnoid space?
No Immunoglobulin, C3/C4 or phagocytes
Delayed response
What are the classic symptoms of Meningitis?
Global headache
Neck and back stiffness
Nausea/Vomiting
Photophobia (non-specific)
What are the symptoms of Meningitis in infants?
Flaccid/Opisthotonus Bulging fontanelle (increased ICP) Fever/Vomiting Strange cry Convulsions Typical signs are often not present <18mo
What common conditions present similarly to Meningitis?
Sub-arachnoid haemmorhage
Malignancy
Other infections
What are the physical signs of Meningitis?
Fever
Petechial/purpuric rash
Photphobia
Irritation of the motor roots
What physical effect does irritation of the motor roots have?
Kernig’s +ve (hamstring spasm)
Neck stiffness
Brudzinskis sign (flexion of neck causes hip/knee flexion)
What is the best diagnostic test in Meningitis?
Lumbar puncture
What are the pros/cons of an LP?
Pros - Distinguish between bacterial/viral, rapid
Cons - Risk of herniation (longer history, focal neurology, drowsy, decreased clotting)
What are the normal CSF values?
Leukocytes - <5 Polymorphs - x Lymphoycytes - x Glucose - 60-80% BG Protein - 0.1-0.4g
Describe the CSF changes present in Meningitis
Increased leukocytes (B>T>V) Presence of neutrophils (B>T>V) Presence of lymphocytes (V>T>B) Decreased glucose (T>B) Raised protein (B>T>V)
What are the most common possible complications of Meningococcal disease?
Death 13% (40% in septicaemia)
Necrotic lesions
Reactive arthrtis (young adults)
Serositis
What are rarer complications of Meningococcal disease?
Neurological sequelae
Abscess formation
What are risk factors for a poor outcome?
Age Presence of otitis media/sinusitis Absence of rash Tachycardia Low GCS \+ve Blood culture Thrombocytopenia Low CSF leukocyte count
How should meningitis be managed?
Antibiotics Oxygenation Prevention of hypoglycaemia/hyponatraemia Anticonvulsants Decrease ICP
What are the ideal antibiotic characteristics for meningitis?
Bactericidal
Sufficient penetration into CSF (non-toxic)
Good activity against pathogens
Little endotoxin released on organism death
What six factors can increase antibiotic penetration of the BBB?
High lipid solubility Low molecular weight Low ionisation High serum concentration Low protein binding Meningeal inflammation
Describe the pros of Chloramphenicol for treating Meningitis
Good CSF penetration (i.v. and oral)
Active against organisms
Describe the cons of Chloramphenicol for treating Meningitis
Bacteriostiatic
Resistance in Hib/Pneumococci
Causes aplastic anaemia/Grey baby syndrome
How is Chloramphenicol used to treat meningitis?
Reserve agent for allergic patients
Describe the pros of Ceftoaxime/Ceftriaxone for treating Meningitis
Good penetration into inflamed CSF
Active against organisms
Active against penicillin resistant pneumococci AND ampicillin resistant Hib
How are Cefotaxime/Ceftriaxone used to treat meningitis?
First line treatment in adults AND children
Cefotaxime - 6 hourly
Ceftriaxone - 12 hourly
Describe the pros of Benzylpenicillin to treat meningitis
Most active agent for penumococcal meningitis
Penetration of inflamed meninges
Describe the cons of Benzylpenicillin to treat meningitis
Short half life (4 hourly dosing)
High serum levels increase risk of epileptic fits
Increasing incidence of resistance
How is Benzylpenicillin used to treat meningitis?
Treatment for known sensitive organisms
4 hourly dosing
What is the penetration ratio for Chloramphenicol?
9:1
What is the penetration ratio for Cefotaxime/Ceftriaxone?
1:10
What is the penetration ratio for Benzylpenicillin?
1:23
What is the antimicrobial therapy for N. meningitidis?
Benzylpenicillin if sensitive
Cefotaxime/Ceftriaxone if not
What is the antimicrobial therapy for S. pneumoniae?
Benzylpenicillin if sensitive
Cefotaxime/Ceftriaxone if not
Add Vancomycin if strain may be resistant
What is the antimicrobial therapy for Hib?
Cefotaxime/Ceftriaxone
What is the antimicrobial therapy for an unknown organism? - Child >2mo and adults
Cefotaxime/Ceftriaxome
Add Amoxicillin if >50 or immunocompromised
What is the antimicrobial therapy for an unknown organism? - Child <2mo
Benzylpenicillin AND Gentamicin
What is the length of treatment for N. meningitidis?
7 days
What is the length of treatment for S. pneumoniae?
14 days
What is the length of treatment for Hib?
7 days
What is the length of treatment for L. monocytogenes?
> 21 days
What is the length of treatment for unknown organisms?
7-14 days i.v. treatment
When does giving steroids improve long-term morbidity?
Hib meningitis in children
Steroids given prior to antibiotics
What three vaccines are available for meningitis?
Conjugated Hib and Meningococcal group C Pneumococcal vaccine (<2 yrs)
Men B vaccine
Polyvalent pneumococcal polysaccharide vaccine
What chemoprophylaxis is available for meningitis?
Rifampicin OR Ciprofloxacin
Define a brain abscess
An abscess caused by inflammation and collection of infected material from local/remote infectious sources within the brain
What are the clinical signs of a Brain abscess?
Focal neurological signs Raised ICP Headache (70-95%, short duration) Fever (variable) Raised CRP/ESR
What are the possible routes of infection for brain abscess causing organisms?
Direct spread (venous connections)
Haematogenous spread
Direct implantation
What organisms cause brain abscesses?
Streptococcus milleri (60-70%) Anaerobes (65%) Enterobacteriaceae (25%) Staphylococcus aureus (10%) Polymicrobial (30-60%)
Describe the pathophysiology of brain abscesses
1-3 days - Cerebritis with central inflammation
4-9 days - Ring of cerebritis surrounding necrotic centre (+/- mass effect)
10-13 days - Capsule formation
14 days - Capsule helps to limit spread
What is the surgical treatment for brain abscess treatment?
Drainage (Burr-hole under LA/Craniotomy)
Excision (Craniotomy)
What is the medical treatment for brain abscess treatment?
Extensive antibiotic coverage
What antibiotic treatment is best if the source is likely dental/sinus/haematogenous? (brain abscess)
Ceftriaxone + Metronidazole
If streptococcal/anaerobic narrow to Benzylpenicillin + Metronidazole
What antibiotic treatment is best if the source is likely otogenic? (brain abscess)
Ceftazidime + Benzylpenicilin + Metronidazole OR
Meropenem
What antibiotic treatment is best for post-operative/post-traumatic treatment? (brain abscess)
Vancomycin + Meropenem
What is the general structure of antibiotic therapy? (brain abscess)
High dose
6-8 wks
3 wks i.v. then oral
What possible side effects are associated with the high doses used for treatment? - Brain Abscesses
Bone marrow suppression
Antibiotic fever
