1
Q
What tissues does meningitis effect?
A
Involves arachnoid, pia matter, and CSF
The inflammatory process in the subarachnoid space can extend around the brain, spinal cord, and ventricles
Inflammation due to infection, tumours, stroke, trauma
2
Q
What is the mortality rate associated with meningitis?
A
Can reach up to 30% (more common in younger patients than adults)
3
Q
What are the two types of meningitis?
A
- Bacterial
- Asceptic
4
Q
What are the general characteristics of bacterial meningitis?
A
- Acute meningeal inflammation caused by infection
- Generally evokes a PMN (largely granulocytes) response within the CSF
5
Q
What are the general characteristics of asceptic meningitis?
A
- Meningeal inflammation without evidence of bacteria (potentially viral, fungal, syphillis, TB, Lyme disease, atypical bacteria, chemical irritation, malignancy or drug-induced)
6
Q
Why does meningitis have such a high mortality rate?
A
Once a causing agent crosses past the many protective mechanisms of the brain (skull, meninges, BBB, blood-CSF barrier), there is a lack of host defence mechanisms (only granulocytes)
7
Q
What are the three mechanisms by which meningitis can develop?
A
- Hematogenous (spread from blood)
- Contiguous (from an URTI like sinusitis or acute otitis media)
- Direct inoculation (surgery or trauma)
8
Q
What are the steps of a meningitis infection?
A
- Mucosal colonization and bacterial invasion of the host and CNS
- Bacterial replication in subarachnoid space
- Inflammation/pathophysiologic changes (recruit more cells, more fluid)
- Increased intracranial pressure, cerebral edema and neuronal damage (main concern in meningitis)
9
Q
What are some bacteria that are responisble for bacterial meningitis?
A
Form immunoglobulin A proteases and encapsulated:
- S. pneumoniae (more than 50%)
- N. meningitidis (14%)
- Group B Strep (18%)
These bacteria colonize the nasopharyngeal mucosa by cleaving certain antibodies
10
Q
What is the consequence of poor host defences in the CSF?
A
- Low complement levels, low antibody levels
- Bacteria are able to quickly multiply
11
Q
How does the inflammatory procees in worsen meningitis?
A
- Cytokines are released
- Cytokines promote migration of neutrophils into the CSF (reduced host defense)
- Neutrophils release prostaglandins, matrix metalloproteases, etc. that cause edema and swelling
12
Q
What are some risk factors for developing meningitis?
A
- Congential or traumatic defects
- Previous viral infection
- Extremes of age
- Low socioeconomic status
- Crowding (orphanage, dorm rooms, etc.)
- Exposures to pathogens
13
Q
What are some situations that can increase exposure to pathogens that cause meningitis?
A
- Recent colonization
- Contact with meningitis patient
- Bacterial endocarditis
- IV drug use
- Surgery or trauma
- Splenic dysfunction
- Immunosupression
14
Q
Where is the CSF produced?
A
Most is produced in ventricles by choroid plexus
15
Q
How does the CSF flow around the brain and spinal chord?
A
It flows uni-directionally from ventricles to subarachnoid space then down through spinal cord
16
Q
Will drug administration into CSF at the lumbar result in well distribution into entire CSF space?
A
No, admin in lumbar area will not result in sig concentrations above that point
17
Q
Does CSF contain a lot of WBCs?
A
No, the CSF contains only some granulocytes (not a lot of WBCs)
18
Q
Is healthy CSF protein-rich?
A
No, usually below 500mg/mL
19
Q
What are the most common pathogens that cause meningitits in premature infants and neonates?
A
- E. coli
- Strep. agalactiae
- L. monocytogenes
- Klebisiella species
20
Q
What are the most common pathogens that cause meningitis in infants and kids?
A
- N. meningitidis
- S. pneumoniae
- H. influenza
21
Q
What are the most common pathogens that cause meninigitis in patients between the ages of 2 and 50?
A
- S. pneumoniae
- N. meningitidis
22
Q
What are the most common pathogens that cause meningitis in patients who are older than 50?
A
- S. pneumoniae
- N. meningitides
- L. monocytogenes
- gram negative enterics
23
Q
What are some common pathogens that cause meningitis in patients who has surgery or trauma?
A
- Staph infection
- gram negative bacilii
24
Q
What are some common pathogens that cause meningitis in patients with abcesses?
A
Polymicrobial (aerobic and anaerobic)
25
What is the classic triad of symptoms for meningitis?
Only seen in 25-50% of patients
1. Headache
2. Fever
3. Neck stiffness (30%)
26
What are some other common signs associated with meningitis?
- Altered mental status
- Malaise
- Seizures (5-28% of adults and 33% of kids)
- Vomiting
27
What are the two physical exams that can help in the diagnosis of meningitis?
Kernig's and Brudzinski's signs
In both, the practitioner flexes parts of the body to stretch meninges and check for pain from inflammation/infection
28
How are the signs and symptoms of meningitis different in infants?
It is often non-specific
- irritability
- lethargy
- poor feeding
- fever
- seizures
- rash
- breathing changes
- bulging fontanelle
29
How are the signs and symptoms of meningitis different in elderly patients?
It is frequently the only sign is altered mental status or confusion (rapid change without signs of stroke)
30
How are lumbar punctures taken?
- Used to obtain fluid for cell counts
- For gram stain and C&S
- The opening pressure and appearance is noted
- Must be careful or do not puncture patients with elevated intracranial pressure (increased risk of damage)
31
What lab tests are commonly performed to confirm meningitis diagnosis?
- CSF gram stain and culture
- CSF chemistry
- CSF WBC count and differential
32
What is the utility of CSF chemistry tests?
- Normal glucose CSF/serum ratio is around 50-60%, but in bacterial meningitis it is lower
- Protein is normally 0.5g/L, but much higher in bacterial meningitis
33
What is the utility of CSF WBC count and differential assays?
Normally, WBC are less than 5 x10^6 cells/L (mostly monocytes)
In bacterial meningitis (WBC are over 500x10^6 cells/L)
34
What is expected for CSF WBC count in patients who are immunocompromised?
No elevation in number in WBC is expected in meningitis in these patients
35
What are some other laboratory tests for meningitis?
- Check for antibodies towards certain bacteria
- CSF lactate levels (increased in infection)
- Check for endotoxins of bacteria
- Electrolytes
36
What are some acute complications (occur during infection) associated with bacterial meningitis?
- Shock
- Respiratory failure/distress/arrest
- Apnea
- Altered mental status/coma
- Increased intracranial pressure
- Seizures
- Disseminated intravascular coagulation
- Subdural effusions
- Subdural abcess
- Intracerebral abscess
- Increased intracranial pressure
- Death
37
What are some complications associated with post-infection meningitis?
Meningitis can damage tissues and leave lasting impact on funciton (sequelae)
- Seizures
- Impaired intellectual functioning
- Impaired cognition
- Personality changes
- Dizziness
- Gait disturbances
- Focal neurologic deficits (deafness, blindness, paralysis, paresis)
38
What are some examples of CNS sequelae?
- Hydrocephalus
- Brain abscess
- Subdural abcess
- Subdural effusuon
- Cerebral thombosis
39
Does mortality rates with meningitis decrease with increasing age?
No, mortality rates actually increase (lowest in children, and highest in elderly)
40
What are some factors that increase mortality rates in meningitis?
- Decreased conciousness at admission
- Sign of increased intracranial pressure
- Seizures within 24 hours of admission
- Extremes of age
- Need for mechanical ventilation
- Delay in treatment
41
What is the impact of inflammation on drug reaching the target site in the brain for meningitis?
Antibiotic penetration will increase with inflammation
Inflammation inhibits efflux pumps, so when inflammation goes away, then more drug leaves the brain so do not reduce dose in response to reduced inflammation until patient is fully recovered
42
What are some examples of antibiotics with therapeutic levels in CSF without inflammation?
- Acyclovir
- Cipro, levoflox, moxiflox
- Fluconazole
- Metronidazole
- Sulfonamide
43
What are some examples of antibiotics with therapeutic levels in meningeal inflammation?
- Ampicillin, pen G, piperacillin
- **Cefotaxime, ceftriaxone**
- Imipenem, meropenem
- **Vancomycin**
44
What antibiotics should be avoided in meningitis treatment?
- Aminoglycosides
- 1st and 2nd gen cephalosporins
- Doxycycline
- Intraconazole
- AmpB
- Beta-lactamase inhibitors
45
What is the impact of CSF on antibiotic activity?
In the CSF; pH, pharmacokinetics, and etc are different
Drugs are rapidly cleared from CSF by efflux
Since the CSF has impaired host defence activity, need to use bactericidal agents
46
How are antibiotics administered in meningitis?
- Intralumbar (into the subarachnoid space)
- Intracisternal (large cavities within the subarachnoid space
- Intraventricular
47
What are some administration tips for antibiotic use in meningitis?
- Use preservative free formulations whenever possible
- May introduce nosocomial infection (try to be aseptic)
- Consider the concentrations of drug, vehicle, additives and volume being administered
48
What are some general considerations for meningitis treatment?
- Start antibiotic immediately
- Empiric therapy is based on age, history, underlying disease and gram stain
- Full doses for the entire course of therapy
- IV administration
- Repeast lumbar puncture 1-2 days to ensure sterilization of CSF (not done if patient has common pathogen and is responding well to therapy)
49
Review slide 46 for duration of antibiotic therapy given different pathogens
50
What are some empiric choices for meningitis in patients under 1 month?
Ampicillin+cefotaxime or ampicillin+AMG
51
What are is the empiric antibiotic choice for meningitis in patients between 1 month to 50 years?
Vancomycin+3rd gen cephalo(cefotaxime or ceftriaxone)
52
What is the empiric antibiotic choice for meningitis in patients over 50?
Vancomycin+ampicillin+3rd gen cephalo (cefotaxime or ceftriaxone)
53
What is the empiric antibiotic choice for meningitis in patients with penetrating trauma or neurosurgery?
- Vancomycin+cefepime
- Vancomycin+ceftazidime
- Vancomycin+meropenem
54
What is the specific antibiotic choice for Streptococcus pneumoniae in meningitis?
- Vancomycin+3rd gen cephalosporin (cefotaxime or ceftriaxone)
- Pen G or ampicillin if pen susceptible
- Alt: meropenem, FQ
55
What is the specific antibiotic choice for Neisseria meningitidis in meningitis?
- 3rd gen cephalo (cefotaxime or ceftriaxone)
- Alt: ampicillin, FQ
56
What is the specific antibiotic choice for Listeria monocytogenes in meningitis??
- Ampicillin, Pen G +/- AMG
- TMP/SMX, meropenem
57
What is the specific antibiotic choice for Streptococcus algalactiae?-
- Ampicillin
- Pen G
- Alt: 2rd gen cephalosporins (cefotaxime or ceftriazone)
58
What is the specifc antibiotic choices for Haemophilus influenzae?
- 3rd gen cephalo (cefotaxime or ceftriaxone)
59
What is the specific antibiotic choices for E. coli?
- 3rd generation cephalosporin
- Cefepime, meropenem, FG, TNP/SMX
60
Are any meningitis antibiotic formulations given orally?
Yes, but ony for neonates
61
What are some drugs used to prevent edema, hydrocephalus, and inflammation?
Mannitol (an osmotic diuretic that can decrease intracranial pressure)
Shunts
Steroids
62
How do shunts work in hydrocephalus?
Shunts are used to drain the excess fluid and relieve pressure due to CSF buildup
Excessive CSF causes the brain to compress, causing serious neurological problems
63
How are shunts inserted?
A catheter is passed into a ventricle of the brain
It is tunneled under the skin, behind the ear, down the neck, and chest and into the peritoneal cavity where the excess CSF is absorbed
64
What is the role of corticosteroids in treatment of meningitis?
Controversial due to anti-inflammaotry effects causing antibiotic penetration to decrease.
Administer before or within 2 hours of antimicrobials to counterbalance the release of inflammatory mediators after destroyed bacteria release toxins
65
Can corticosteroids be used if meningitis is not caused by the common pathogens?
No, d/c within 48 hours if H influenzae or Strep pneumoniae are **not cultured**
66
What is the benefit of using corticosteroids in meningitis treatment?
The following only apply if the patient's meningitis is due to H. influenzae or Strep. pneumoniae
- Shown to decrease hearing loss in kids
- Significant decrease in adulrs and reduced hearing loss
67
What is the transmission rates for meningitis between household members?
5% (risk after exposure is 500x higher than general population)
68
What is done to prevent meningitis to spread between close contacts?
Prophylactic treatment is initiated for high risk contacts (household or close contacts, intimate contacts, use the same utensils, school/daycare contacts)
These contacts are within the prior seven days before patient got sick
Counsel patient to watch for fever, rash, confusion, or any other sign/symptoms of meningitis
69
If HCPs are in close proximity to the patient infected with meningitis, do they need to use prophylaxis?
Not really, only if they have had direct mucosal contact with secretions
Counsel patient to watch for fever, rash, confusion or any other sign/symptoms of meningitis
70
Review slide 62 for meningitis prophylaxis doses
71
What antibiotic is given for prophylaxis in meningococcal meningitis?
Rifampin
Alternate choices:
- Ciprofloxacin
- Ceftriaxone
72
What antibiotic is given for prophylaxis in H. influenzae meningitis?
Rifampin
73
What antibiotic is given for prophylaxis in Pneumococcal meningitis?
Prophylaxis is not given for pneumococcal meningitis
74
Review 69 for meningitis case
PHAR 255
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