M- Bacterial Meningitis; Pathogens Flashcards
You arrive to babysitting and the 4 year old is feeling “under the weather”.
On physical exam, he has a fever.
Pupils are equal, round and reactive to light. His lungs are clear but he is slightly tachycardic.
He does not respond to painful stimuli and when you put your hand under his head to pick him up, he groans and his neck doesn’t flex.
What are you concerned that he has?
What will the lumbar puncture show?
Based on his age, what is the most likely causative organism?
Meningitis- nuchal rigidity
Proteins = over 100
Glucose = >40
Few RBCs
high WBCs with 55% neutrophils, 7% lymphocytes, 20% bands
Based on his age:
- s. pneumoniae
- n. meningitidis
- h. influenza b
What 3 bacterial agents of meningitis are most likely to infect infants, children and adults?
How are they usually acquired?
- strep pneumoniae
- n. meningitidis
- h. influenzae b [not really anymore due to vaccine]
They are acquired by respiratory droplets
What 3 bacterial agents are most likely to cause meningitis is neonates?
How are they acquired?
- S. agalactiae [group B strep]
- listeria monocytogenes
- E. coli
They are acquired from the maternal genital tract
A patient comes in presenting with nuchal rigidity, fever, and headache. Based on the high protein content, low glucose, and high WBCs in the CSF, you are concerned about meningitis.
You do a standard gram stain of the CSF and see gram-positive lancet-shaped diplococci with clearing around them.
When you culture the organism it is a-hemolytic on blood agar. What organism is responsible for the meningitis?
What are other lab features of this organism?
Streptococcus pneumoniae
- gram positive cocci in pairs or chains
- alpha hemolytic
- catalase negative
- sensitive to optichin [p-disk]
- sensitive to bile lysis
What disease presentations can occur with a s. pneumoniae infection?
- pneumonia
- sinusitis
- otitis mediahat
- bacteremia
- peritonitis
- meningitis [many of which will also be bacteremic]
What 2 risk factors are seen in most current cases of s. pneumoniae meningitis?
What are some of the other, more infrequent risk factors?
- cochlear implants
- CSF leak
Iatrogenic and trauma breach the BBB from the nasopharynx and allow the introduction of the organism into the subarachnoid space
- extremes of age
- alcoholism, diabetes, HIV
- recent acquisition of a new strain
- defects in humoral immunity
- asplenia/hyposplenia [due to caspulated organism]
What 2 factors associated with s. pneumoniae aid it virulence and pathogenesis?
- pneumolysin
- expressed on invasive strains
- pore forming cytotoxin
- lytic to host cells [macrophages and neutrophils]
- impairs respiratory burst in neutrophils
- induce inflammatory cytokines - polysaccharide capsule
- major virulence factor
- prevents phagocytosis
- negative charge inhibits complement and opsonization by IgG
How does pneumolysin aid in the pathogenesis of s. pneumoniae?
It is expressed on invasive strains and:
- is a pore forming cytotoxin
- lyses host cells [macrophages, neutrophils]
- inhibits neutrophilic respiratory bursts
- induces inflammatory cytokines
How does the polysaccharide capsule aid in the pathogenesis of s. pneumoniae?
It is the major virulence factor and:
- is anti-phagocytic
- the highly negative charge prevents binding of CR3 and iC3b disrupting complement
- inhibits iteraction of FcR and Fc portion of IgG preventing opsonization
Describe the steps in the pathogenesis of s. pneumoniae as it relates to meningitis.
How does it get to the brain?
- direct transfer from the mastoid/sinuses or hematogenous spread
- in the CSF s. pneumoniae goes through spontaneous autolysis releasing factors that activate macrophages
- macrophages release cytokines that attract neutrophils into the CSF
What are the 2 main ways to diagnose S. pneumoniae meningitis?
What is treatment? How is it given?
How can it be prevented?
Diagnosis:
- Culture the CSF or blood
- Rapid-antigen detection test for CAP or meningitis using urine and/or CSF
Treatment:
Vancomycin and cephalosporin in high dose, IV
[you use both agents because there is freq. drug resistance]
Prevented:
Kids –>13 valent conjugate vaccine
Adults–> 23 valent polysaccharide vaccine
A 62 year old man has had a renal transplant 5 years ago. He is rushed to the hospital from work after becoming confused.
He has a slight fever, is mildly tachycardic, but is normotensive and has good O2 saturation.
He is not oriented x3, has nuchal rigidity, and vomited 2x since arriving at the hospital.
LP shows protein over 100, glucose under 40, elevated WBC [mostly lymphocytes].
Does he have meningitis, meningoencephalitis, or encephalitis?
meningoencephalitis
You do a smear for a patient suspected of meningoencephalitis and note:
- gram positive rods
The culture on sheep agar reveals a B-hemolytic pattern.
What organism do you suspect?
What are other important laboratory features of this organism?
What are the unique growth requirements?
Listeria monocytogenes
- gram positive rod
- B hemolytic
- non spore forming
- tumbling motility
Grows in:
- cold temperatures [deli meat at refrigerator temp]
- high salt concentration [7m]
- survive over a wide range of pH
What is the most common presentation of listeria monocytogenes?
Diarrhea
- transient/undiagnosed
- nausea/vomiting
- epidemic gastroenteritis
What CNS infections can be caused by listeria monocytogenes?
- meningitis
- meningoencephalitis
- cerebritis
- brain abscesses
Who are the 2 most “at risk” populations for listeria monocytogenes infections? Why?
- pregnant women
- immunocompromised individuals
- transplant
- steroids
- HIV/AIDS
It preferentially infects them because:
- Listeria is spread by food-borne illness, NOT person to person
- BROAD DISTRIBUTION - wild animals, birds, human intestinal carriers, etc which is more likely to infect ppl with poor immune systems
How is neonatal listeriosis acquired? [transplacentally, during birth, etc]
When will it present in the neonate?
What will be the signs/symptoms? What should you do immediately?
It is acquired transplacentally.
The neonate will present with symptoms 24 hrs to 6 days after birth
- loss of appetite
- lethargy
- jaundice
- vomiting
- respiratory distress
- shock
- *** hypothermia is common
Immediately do a lumbar puncture on a fussy baby because they can’t tell you if their neck hurts
What happens of the mother gets a listeria monocytogenes infection in the third trimester of pregnancy?
- abortion
- stillbirth
- premature birth
How many cases of invasive listeria monocytogenes occur per year in the US?
What percent are in pregnant women?
What is the mortality rate?
2500 cases/year in the US
30% in pregnant women [most have mild symptoms despite bacteremia]
Mortality rate is 20-30% and is the 2nd leading cause of meningitis is 60 years
How does listeria evade the immune system when it is in the host?
- gets into phagosomes but prevents it from forming a phagolysosome
- breaks down the phagosome and forms actin “rockets”
- uses actin to propel itself directly into an adjacent cell so it is never exposed to Ab outside of cells
What drugs do you use to treat listeria monocytogenes CNS infection?
vanc and cephalosporin used for strep pneumonia is not broad enough to cover listeria.
you need to add ampicillin to the cocktail
An 18 year old freshman in college has nuchal rigidity, a headache and feels feverish. He goes to bed. In the morning, his roommates find him unresponsive.
He becomes tachycardic, hypotensive, hypoxic, and gets multiple purpuric lesions all over his body.
Labs show 23000 WBC in the blood, with low platelets.
Lumbar puncture shows protein over 100, glucose below 40, extremely elevated WBCs that are mostly neutrophils (80%).
Does this patient have meningitis, or meningoencephalitis?
Based on the history/physical/age group, what is the suspected organism?
We cant tell if there is meningitis or meningoencephalitis because the patient is unresponsive [thus not allowing us to check for neurological deficits]
Based on the college scenario, we would say the probable organism is N. meningitidis
In a patient with suspected meningitis, you do a gram stain of the CSF and note gram negative diplococci with ‘halo”. What is the most likely organism?
What are other lab features of this organism?
What are the ideal growth conditions?
N. meningitidis
- gram negative diplococci
- catalase and oxidase positive
Growth conditions:
- optimal growth at body temp [35-37]
- require CO2 for optimal growth
What are the 4 major antigenic components of N. meningitidis?
- pili -necessary for attachment to the host cells
- LOS- reduce complement and Ab binding and phagocytosis
- outer membrane proteins [porins, opa]
- polysaccharide capsule -reduce complement and Ab binding and phagocytosis
*can survive inside neutrophils or free in the blood
How is N. meningitidis transmitted?
How many cases occur each year in the US?
What ages are preferentially affected?
It is an obligate human pathogen transmitted via aerosol
- 1000 cases/year in the US
- affects all ages [with peaks at 6 months, 15-25 years]
How are the serogroups for N. meningitidis determined? What are the 5 main kinds?
Which are convered in the FDA-approved vaccine?
Serogrouping is determined by the polysaccharide capsule.
A. C, W135 and Y are covered by the vaccine [B is not]
Describe the polysaccharide capsule of serogroup B N. meningitidis.
How does this affect prevention/treatment?
It is n-acetyl- neuraminic acid.
It mimics the polysaccharide found in human cells. This makes it difficult to use in the standard vaccine because then the body will make antigens that have cross-reactivity to self.
*there is a non-FDA approved vaccine that uses outermembrane proteins of serotype B rather than the polysaccharide capsule
What 3 major CNS involved syndromes are caused by N. meningitidis?
- meningitis (70%)
- meningitis with meningococcemia [fulminant disease with purpura etc]
- meningococcemia alone
What are the sequelae/complications of n. meningitidis?
- hearing loss
- amputation [from the purpura]
- Freiderich Waterhouse - infarction of adrenals
- myocardial involvement
What is the ages are the peaks on the bimodal age distribution of N. meningitidis infections?
What is the most likely reason?
Peaks at 6 months and a smaller peak at 15-25.
This is because acquisition of a NEW STRAIN causes presentation of N. meningitidis
How does n. meningitidis penetrate the BBB to interact w/ the meninges–> meningitis?
- lipid microdomain formation rearranges the cytoskeleton of meningeal cells to allow the bacteria to resist shear stress
- cytokine damage may increase bacterial transcytosis
- cytokine release following interaction of bacteria with the leptomeninges leads to meningitis
How is N. meningitidis diagnoses and treated?
Diagnosis:
- CSF gram stain
- culture of CSF or blood
- PCR
Treatment:
- pen G
- 3rd generation cephalosporins
How do we prevent n. meningitidis infections?
- polysaccharide vaccines [ACW125Y]
- diptheria toxoid conjugate for 11-55
- non-licensed outermembrane protein vaccine for serogroup B
How do we prevent spread of n. meningitidis to people in close contact with those infected [family, schoolmates, hospital staff]?
Eradication of carriage with
- rifampin
- ciprofloxacin
- ceftriaxone
