Kozel: CNS Infections Flashcards
List 5 routine CSF tests
- WBC with differential
- Glucose concentration
- Protein concentration
- Gram stain
- Bacterial culture
What should the [glucose] be in the CSF?
60% of plasma levels - 50-80mg/dL
In viral meningitis, what will WBC count be? What type of cell will be infiltrating? What will glucose levels be like? Protein levels?
WBC: 50-1000
Cells: mononuclear
Glucose: >45
Protein: <200
In bacterial meningitis, what will WBC count be? What type of cell will be infiltrating? What will glucose levels be like? Protein levels?
WBC: 1000-5000
Cells: neutrophilic
Glucose: <40
Protein: 100-500
In tuberculous meningitis, what will WBC count be? What type of cell will be infiltrating? What will glucose levels be like? Protein levels?
WBC: 50-300
Cells: mononuclear
Glucose: <45
Protein: 50-300
In crytococcal meningitis, what will WBC count be? What type of cell will be infiltrating? What will glucose levels be like? Protein levels?
WBC: 20-500
Cells: mononuclear
Glucose: 45
If the WBC count is elevated in CSF, what does this imply?
inflammation and immune response
If glucose is decreased in the CSF, what are three potential causes?
- increased glycolysis by leukocytes and bacteria
- increased metabolic rate of brain and spinal cord
- altered glucose transport b/w blood and CSF
If protein is increased in the CSF, what does this imply?
disruption of BBB
When is a lumbar puncture contraindicated?
- papilledema - increased cranial pressure
2. neurological suggestion of intracranial mass
inflammation of protective membranes covering brain and spinal cord – meninges
acute meningitis
any meningitis for which a cause is not apparent after routine stains and culture of CSF
aseptic meningitis
Symptoms of acute meningitis? Start with the triad of symptoms…
headache, neck stiffness + fever
confusion and altered mental status
vomiting
photophobia or phonophobia
What are 3 steps in the initial management of acute meningitis?
- lumbar puncture + CSF analysis
- empiric antimicrobial therapy based on patient age
- may use dexamethasone if appropriate
Viruses are the most common cause of meningitis. List 3 viruses that can cause acute meningitis.
- enteroviruses
- mumps virus
- herpesvirus
5 bacterial causes of acute meningitis?
- S. pneumo
- N. meningitidis
- S. agalactiae
- H. influenzae
- L. monocytogenes
2 spirochetes that can cause acute meningitis?
Treponema pallidum
Borrelia burgdorferii
Mucosal/nasopharyngeal colonization
Local invasion
Intravascular survival
Meningeal invasion – Moxon experiment
Induction of subarachnoid space inflammation
Alterations of blood-brain barrier
Cerebral edema and increased intracranial pressure
Vasogenic – increased BBB permeability
Cytotoxic – swelling of cellular elements of brain
Interstitial – obstruction of normal flow of CSF
bacterial meningitis
Bacterial meningitis can induce inflammation of the (blank) and may alter the (blank)
subarachnoid space; BBB
At a young age (<1 month - 23 months), what bacteria are most likely to cause meningitis?
Strep agalactiae
E. coli
At an “older age” (2-50+ years), what bacteria are most likely to cause meningitis?
S. pneumo
N. meningitidis
How do antibiotics penetrate the BBB?
inflammation disrupts BBB
What do corticosteroids do in cases of meningitis?
reduce inflammation, reduce CNS penetration
**antibiotics less likely to get across BBB
What are features of antibiotics with good BBB penetration in absence of meningeal inflammation?
low molecular weight low degree of ionization at phys pH high lipid solubility low degree of protein binding absence of active efflux systems
If <1 month, how should you treat bacterial meningitis?
ampicillin + cefotaxime (binds PCPs and blocks cell wall synthesis)
or
ampicillin + an aminoglycoside (blocks 30s ribosome)
If 1 month to 50 years old, how should you treat bacterial meningitis?
vancomycin + third gen cephalosporin
If 50+, how should you treat bacterial meningitis?
vancomycin + ampicillin + third gen cephalosporin
For a patient with meningitis caused by Strep pneumo, prescribe (blank)
vancomycin + third gen cephalosporin
For a patient with meningitis caused by Neisseria meningitidis, H. influenzae, or E. coli, prescribe (blank)
third gen cephalosporin
For a patient with meningitis caused by Listeria monocytogenes or Step agalactiae, prescribe (blank)
ampicillin or penicillin G
How is chronic meningitis different from acute meningitis?
- onset is more gradual
- fever is lower
- associated with lethargy and disability
- often immunocompromised
What can cause chronic meningitis?
mycoses - cyrptococcosis, coccidiomycosis, histoplasmosis, candidiasis
bacteria - M. tuberculosis, T. pallidum, B. burgdorferi
parasites
Inflammatory process of the brain parenchyma
Clinical or lab evidence of neurologic dysfunction
encephalitis
Symptoms of encephalitis?
fever and headache
**altered mental status
What will the CSF be like in encephalitis?
increased lymphocytes (lymphocytic pleocytosis) normal glucose (as opposed to increased in bacterial meningitis) elevated protein
What most commonly causes encephalitis?
viruses: herpesvirus, arboviruses, HIV, enteroviruses, rabies virus
focal, intracerebral infection that begins as a localized area of cerebritis and develops into collection of pus surrounded by a well-vascularized capsule
brain abscess
What are 3 sources of brain abscess?
- contiguous spread - sinusitis, otitis media
- hematogenous
- trauma
Symptoms of brain abscess?
headache
nausea
vomiting
focal neuro findings
**varies with site of abscess
When bacteria are involved in brain abscesses, it’s usu a mixed infection. Which organisms are involved in most cases of brain abscess?
- streptococcus spp (70%)
2. S. aureus (10-20%)
Which fungi are most commonly involved in a brain abscess?
Aspergillus Candida Crypto Mucorales Coccidioides
T/F: The bacteria involved in brain abscesses vary depending on the predisposing conditions, ex: sinus infection vs penetrating trauma will involve different bacteria.
True
What three mediums can be used to isolate Neisseriaceae?
blood
chocolate agar
Thayer-Martin medium **inhibits normal flora
What do Neisseriaceae produce, which can be used for identification?
indophenol oxidase
Meningitis is predominantly found in this area
sub-Saharan Africa
What is the classic epidemic strain of N. meningitidis?
Group A capsular polysaccharide
3 antigenic structures of N. meningitidis?
Group specific capsular polysaccharide
Type specific outer membrane protein
Type specific lipooligosaccharide
What are 3 meningococcal infections?
- meningococcemia - may occur with or w/o meningitis
- meningitis
- petechial lesions
4 virulence factors of Neisseria meningitidis?
- antiphagocytic capsule
- lipooligosaccharide
- outer membrane proteins
- pili
Extremely toxic virulence factor of Neisseria meningitidis; produces inflammation; contains lipid A and core oligosaccharide; released from the bacterial surface as membrane blebs
lipooligosaccharide
Where does N. meningitidis adhere in carriers? How does it adhere? It can remain local, but it can also spread. Where does it spread?
to the nasopharynx; adheres via pili; spreads via lymphatics to blood and meninges
What does the capsule of N. meningitidis do?
prevents phagocytosis and complement mediated lysis
What does lipooligosaccharide cause?
tissue damage and DIC
Multiple attacks of N. meningitidis are associated with deficiencies in (blank)
terminal complement proteins - C5-C9
What are some ways in which you can identify N. meningitidis in the lab?
- specimens: blood, CSF, nasopharyngeal secretions
- direct examination: gram stain of CSF
- isolation: culture, incubate in CO2, grow on blood agar, Thayer Martin, or chocolate agar
What are some differential tests that can be used to confirm N. meningitidis infection?
gram negative diplococci
oxidase positive
oxidative production of acid from sugars like glucose
How is N. meningitidis transmitted?
man to man transmission via airborne droplets
Who is most susceptible to N. meningitidis infections?
young children (lack antibody) college students military recruits (crowding, fatigue) microbiologists w potential exposure travelers to endemic regions people with terminal complement deficiencies no spleen
Meningococcal disease is most likely to occur during months (blank) to (blank) of life as transplacental antibody is wearing off
6-12 months
What is the major factor that determines if a person is resistant or susceptible to meningococcus infection? How do you get protection to different types of capsular antigen? What explains the risk of childhood infection b/w ages 6-24 months?
anticapsular antibody; exposure in our normal flora to something that looks like that polysaccharide antigen; lack of antibody explains the risk of children b/w 6-24 months
How is the meningococcal vaccine different now than it was in 1981?
it used to be a purified polysaccharide alone, but now it is a polysaccharide-protein conjugate vaccine; also the vaccine is now routinely given at 11-12 years of age with a booster at 16-18 years
What type of vaccine is the meningococcus vaccine?
multivalent purified capsular polysaccharide - capsular polysaccharide-protein conjugate
What is the standard therapy for N. meningitis if it is identified?
third generation cephalosporin ex: ceftriaxone/cefotaxime
or
penicillin G or ampicillin
**readily penetrates inflamed meninges
What can be used for family contacts of those with meningitis or in epidemic cases?
chemoprophylaxis - rifampin (disrupts RNA polymerase)
How to treat meningitis if <1 month old?
ampicillin + cefotaxime
or
ampicillin + aminoglycoside
How to treat meningitis if 1-50 years old?
vancomycin + third gen cephalosporin
How to treat meningitis if >50 years old?
vancomycin + ampicillin + third gen cephalosporin
Describe Hemophilus influenzae morphologically
very small gram negative rods
2 nutritional requirements for H. influenzae?
X factor - hematin; found in blood
V factor - NAD
What type of agar is good to grow H. influenzae? What must be done to the blood agar? What is another way to grow H. influenzae?
chocolate agar; it must be heated to lyse RBCs and release factors X and V; you can also grow it in the presence of S. aureus - this is called satelliting
Grows with S. aureus - satelliting - releases X and secretes factor V
H. influenzae
What is the antigenic structure notable on H. influenzae?
capsular polysaccharide - types a-f
**not all strains have a capsule - some are nontypeable
This type of H. influenzae polysaccharide causes almost all systemic/invasive disease; polyribitol phosphate
type b
What does H. influenzae infection cause?
nasopharyngitis extending to middle ear, blood and meninges, or joints (usu due to nontypeable strain)
epiglottitis (due to encapsulated strains)
pneumonia (not common)
Headache + nuchal rigidity + fever + altered mental status is more indicative of (blank)
encephalitis
Two virulence factors of H. influenzae?
antiphagocytic capsule
endotoxin which induces meningeal inflammation
Where to get a specimen for H. influenzae?
nasopharyngeal swab
blood
CSF
What does culture of H. infleunzae require?
X and V factors
chocolate agar
or S. aureus - satellite phenomenon
H. influenzae colonizes the (blank), and is usually a (blank) strain
upper resp tract; nontypeable
**requires type b to cause invasive disease
Why are most of us >3yo resistant to H. influenzae?
natural antibody which protects by opsonization and complement mediated lysis;
Maternal antibody protects < 6 months
Exposure to Hib carriers and cross-reactive antigens protects children > 3 yrs
What type of vaccine is the H. influenzae vaccine?
capsular polysaccharide-protein conjugate
How to treat Hib infection?
prompt vigorous treatment with a broad spectrum cephalosporin with good CNS penetration (ex: cefotaxime or ceftriaxone)
What to give carriers of Hib infection?
rifampin
What to give susceptible contacts of those with Hib infection?
chemoprophylaxis
What does H. influenzae biogroup aegyptius cause?
Brazilian purpuric fever - acute onset of fever, vomiting, abdominal pain, followed by purpura, vascular collapse and death
What does Hemophilus aegyptius cause?
acute, purulent conjunctivitis (pink eye)
What does Hemophilus ducreyi cause?
chancroid (soft chancre) - painful ulcers on genitalia
Where is Hemophilus ducreyi commonly seen?
in Africa
**probable co-factor in transmission of AIDS
