Bacterial Meningitis Flashcards
Describe bacterial meningitis
This is considered a medical, neurologic and sometimes neurosurgical emergency
The incidence varies throughout the world with it being rare in the west and much more common in the meningitis belt of Africa
What is meningitis?
Infection of the meninges – membranes that line the brain and spinal cord
What things cause acute meningitis, marked by quick onset, and a quick progression?
bacteria and viruses
As opposed to TB/Crypto (subacute).
How does meningitis occur?
Following colonization (commonly of the mucous membranes of the respiratory tract), there is invasion into the bloodstream and eventual entry into the subarachnoid space (Direct spread to the CNS also occurs after sinusitis and otitis media)
Subsequent inflammation and neurological damage ensues
Why is the CNS so susceptible to inflammation and neurological damage?
- Subarachnoid space has lack of host defenses
- Bacterial components recognized, cytokines (TNFα, IL-6, and IL-1) released
- Neutrophils then cross the BBB and bacterial lysis occurs leading to release of more pro-inflammatory agents
T or F. Many cytokines are released in greater quantity in pneumococcal meningitis than in meningitis caused by other organisms
T. and could account for the worse prognosis associated with pneumococcal meningitis.
What are the classic symptoms of meningitis?
Fever, nuchal rigidity, and AMS (occurs in <50%)
–Any 2 of HA, nuchal rigidity, fever or AMS much more common – up to 95% of patients
What are some other findings with bacterial meningitis?
vomiting, photophobia, seizures, focal neurologic deficit (eg. Cranial nerve palsies), papilledema
Petechiae and purpura are classic with meningitis due to what organism?
N. meningitidis
What is a Brudzinski sign?
with patient in supine position, passively flex head towards the chest. Test is positive when there is flexion of the knees and hips.
Tests are not good. Kernig and Brudzinski: 5% sensitivity for meningitis
What is a Kernig sign?
–patient is supine with hip flexed at 90°. Attempt to extend the leg at the knee. Test is positive when there is resistance to extension a the knee or pain in lower back or posterior thigh
.
What is Jolt accentuation of HA?
–Jolt accentuation of HA: patient rotates his/her head horizontally 2-3 times per second. Test is positive if patient reports exacerbation of headache
Jolt accentuation: conflicting studies. Initially looked better but more recent study showed sensitivity of 21%
How is bacterial meningitis diagnosed?
Most important and should be done as soon as possible: Lumbar puncture for CSF (gold standard). Should be done before antibiotics if possible.
Other options: routine labs (elevated WBC count, possible thrombocytopenia, possible DIC), blood cultures (especially if LP is delayed until after ABX have been given)
_____% of patients with bacterial meningitis will have positive blood cultures
50-90%
Sometimes if there is a possibility of a mass lesion or increased ICP, head CT is indicated prior to LP being done for diagnosies. If not and there is increased ICP, LP could cause brain herniation.
Reasons for obtaining head CT prior to LP:
Immunocompromised state (eg, HIV infection, immunosuppressive therapy, solid organ or hematopoietic stem cell transplantation)
●History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection)
●New onset seizure (within one week of presentation)
●Papilledema
●Abnormal level of consciousness
●Focal neurologic deficit
What CSF findings suggest bacterial meningitis?
–High opening pressure (normal 10-20 cm H2O)
–High WBC (neutrophil predominant) (chemotactic response) (normal 0-5)
–High protein (blood-brain-barrier breakdown) (normal 15-45)
–Low glucose (host stress response) (normal is 2/3 the plasma glucose)
Bacterial meningitis example:
Opening pressure 30 cm water
WBC 100-50,000
Protein 150
Glucose 30 (serum glucose 100)
How sensitive are CSF gram stain and culture for bacterial meningitis?
Gram stain sensitivity 65-80%, culture about 80% sensitive
What are the most common causes of bacterial meningitis in newborns (less than 1 month)?
GBS
E. Coli
Listeria
What are the most common causes of bacterial meningitis in children 1-23 months old?
S. pneumo
N. meningitis
H. influenzae
GBS, E. Coli, Enteroviruses
What are the most common causes of bacterial meningitis in people 2-50 yo?
S. pneumo
N. meningitidis
Enteroviruses
HSV
What are the most common causes of bacterial meningitis in people 50+ yo?
S. pneumo
Aerobic Gram negative rods
Listeria
N. meningitidis
How is newborn (less than 1 month) bacterial meningitis tx?
Give antibiotics as soon as possible. Early treatment associated with lower mortality
Ampicillin plus Cefotaxime or
Ampicillin plus aminoglycoside such as Gentamicin
How is 1 month-50 yo bacterial meningitis tx?
Give antibiotics as soon as possible. Early treatment associated with lower mortality
–Vancomycin plus 3rd generation cephalosporin (either Ceftriaxone or Cefotaxime)
–Add ampicillin if Listeria is suspected
How is 50+ yo bacterial meningitis tx?
–Vancomycin plus 3rd generation cephalosporin plus Ampicillin
Give antibiotics as soon as possible. Early treatment associated with lower mortality
Empiric tx special situations: Suscepted bacterial meningitis with basilar skull fracture/cribiform plate fracture:
Vancomycin plus Cefotaxime or Ceftriaxone
Empiric tx special situations: Suscepted bacterial meningitis with head trauma, neurosurgery, or CSF shunt:
Vanco + Ceftazidime, Cefepime, or Meropenem
What are some other helpful tx modalities?
•Adjunctive corticosteroids: Confers a significant mortality benefit in those with pneumococcal meningitis and a possible mortality benefit in patients with bacterial meningitis due to other organisms
–Possible reduction in hearing loss and other neurologic sequelae
–Give first dose of steroids before or with first dose of antibiotics. Continue for 4 days for bacterial meningitis due to any cause.*
Describe Strep pneumo
Gram positive, lancet shaped (oval with pointed ends), encapsulated diplococcus (below)
•Optochin sensitive
•Catalase negative
•Quellung reaction
Strep pneumo
Alpha hemolysis (partial hemolysis): form green ring around colonies.
Optochin sensitive
Catalase negative: Distinguishes staph from strep. Catalase catalyzes the decomposition of hydrogen peroxide to water and oxygen
What is the Quellung rxn seen with Strep pneumo
With type-specific antiserum, the capsules swell (another distinguishing characteristic)
What virulence factors does Strep pneumo have?
–Polysaccharide capsule. Interferes with phagocytosis and promotes invasiveness. (No virulence without the capsule. More than 90 antigenically distinct types.)
–IgA protease: enhances organism’s ability to colonize the URT.
–Lipoteichoic acid: activates complement/induces cytokine production
__-__% of the population are colonized with S pneumo in the oropharynx.
5-50%. Not communicable. Healthy people are typically resistant to infection.
What are the risk factors for S. pneumoniae infection?
–Alcohol/drug intoxication (causes cerebral impairment, depressing cough reflex and increasing aspiration of secretions)
–Abnormality of the respiratory tract (viral infection, bronchial obstruction, respiratory tract injury)
–Abnormal circulatory dynamics (pulmonary congestion, heart failure)
–Splenectomy and Sickle cell disease (autosplenectomy)
–HIV infection
How does S. pneumo cause meningitis?
There is initial colonization (adheres tightly to the nasopharyngeal epithelium), followed by invasion (predisposing factors may allow progression to the middle ear or down the respiratory tract to the lungs). Vascular permeability can be altered and allow invasion into the bloodstream
How does S. pneumo reach the CNS?
- Bacteria can cross the BBB by binding to cerebral capillaries, transmigrate and enter the CSF leading to meningitis
- OR
- Direct spread to CNS after otitis media
________ is the most common cause of meningitis in the united states
S. pneumo
How is S. pneumo meningitis tx?
- Vancomycin plus Ceftriaxone
- Adjunctive steroids
What vaccines are available for Strep pneumo?
1) Prevnar 13 (Infants receive 4 doses betwen 6 weeks and 15 months; Adults 19-65 can get if needed)
2) PPSV23 (apporved for children 2+ with specified needs, adults 19-65 as needed, and all adults 65+)
Describe Neisseria meningitidis
Gram negative diplococci (humans are only host) that is transmitted by airborne droplets
Ranks 2nd to strep pneumo as cause of meningitis but is most common cause in those age 2 years to 18 years.
How does N. meningitidis reach the CNS?
–Colonize the membranes of the nasopharynx and become part of transient flora of URT (carriers are usually asymptomatic)
–Organism can enter bloodstream and spread to the CNS
N. meningitidis can cause outbreaks. What are some common populations in which this occurs?
Carriage rates is about 5%, can be up to 35% in people who live in close quarters – military recruits, dorms. Can cause outbreaks, either small or epidemics.
What virulence factors does N. meningitidis have?
- polysaccharide capsule
- Lipooligosaccharide (LOS)- major toxin of N. meningitidis; caused shock and fever
- Pili
- Opacity proteins (Also play a role in attachment to respiratory epithelium)
- Human factor H binding proteins (FHBP)
More on the polysaccharide capsule of N. meningitidis
–Strains are grouped on the basis of their capsular polysaccharides into 12 serogroups
- Most important serogroups associated with disease in humans: A, B, C, Y and W135
- Serotype A: leading cause of epidemic meningitis worldwide
- Serotype B accounts for most disease in the U.S. Group B polysaccharide is not immunogenic in humans and is not part of the vaccines that contain the capsular polysaccharide of the other 4 groups
What does having Pili allow for N. meningitidis?
Attachment of epithelial cells in the nasopharynx is mediated by pili. Invasion of mucosal cells involve phase variation (turning off of genes) then turning genes back on once invasion into the bloodstream is complete; also undergo antigenic variation
What does Human factor H binding protein (FHBP) do?
Binds factor H, an inhibitor of complement factor C3b. Presence of Factor H on surface of the bacteria reduces the opsonizing activity of C3b and reduces amount of membrane attack complex produced.
What other very important virulence factors does N. meningitidis have?
•Phase variation: Changes in expression states of a gene leading to “on-off” control
•Antigenic variation: Changes in genes leading to expression of different forms of similar genes
How does N. meningitidis meningitis present?
–Sudden onset of fever, nausea, vomiting, headache, decreased ability to concentrate, and myalgias in an otherwise healthy patient
–Classic triad of fever, AMS, nuchal rigidity in about 25%
Note that N. meningitidis can present with three distinct neurological syndromes:
Meningitis
Meningitis with accompanying meningococcemia
Meningococcemia without clinical evidence of meningitis
How does N. meningitidis induced Meningococcemia (bloodstream infection/sepsis) present?
–Rash (nonspecific to petechial to purpuric), cold hands and feet, leg pain, shock, DIC
–Fever, n/v, difficulty to arouse
_____ may be an important differential sign for N. meningitidis induced meningitis and occasionally the pain is quite intense. These are generally more painful than myalgias seen in viral influenza. Disease progression is usually quite rapid with transition from health to severe disease in a matter of hours.
Myalgias
Late winter months.
The presentation of N. meningitidis meningitis can also include what?
Purpura fulminans:
–Severe complication of meningococcal disease
–Occurs in 15-25% of those with meningococcemia
–Acute onset of cutaneous hemorrhage and necrosis due to vascular thrombosis and DIC
How does meningococcal disease present?
Earliest clinical signs: fever, headache, loss of appetite, nausea, vomiting, and upper respiratory symptoms, such as sore throat and coryza)
- Can be very difficult to recognize and diagnose early in the course of disease
- Classic clinical features of meningococcal disease (eg, hemorrhagic rash, meningismus, and impaired consciousness) appear late in the illness
What is Waterhouse-Friderichsen syndrome?
Adrenal infarction can cause adrenal insufficiency that follows N. meningitidis infection
How is N. meningitidis tx?
- Once the diagnosis is seriously considered (either meningitis or meningococcemia), no more than 30 minutes should elapse before administering antibiotic. Either Cefotaxime or Ceftriaxone
- If organism is penicillin susceptible, can switch to penicillin if desired
- +/- dexamethasone
- Close contacts of those infected should receive prophylaxis (Cipro, Rifampin or Ceftriaxone)
What vaccines are available for N. meningitidis?
Menactra and Menveo (quidrivalent vaccines active against serotypes A,C,Y, and W135) - either is recommended for ALL people 11-18 years old and those 2-10 and 19-55 at increased risk
-Trumeba (MenB-Fhbp) and Bexsero (MenB-4C)- vaccines against serogroup B for those 10-25 yo
Describe Listeria monocytogenes
A gram + rod, facultative intracellular that exhibits unsual ‘tumbling’ movement intracellularly (distinguished from corynebacteria)
T or F. Listeria monocytogenes grows well at cold temperatures
T. Those at risk: neonates, elderly, immunosuppressed (especially those with defects in cell-mediated immunity)
Describe the pathogenesis of Listeria monocytogenes
Infection depends on the ability to invade and survive within cells. Invasion of cells is mediated by internalin and E-cadherin on the surface of human cells
The ability of Listeria to pass the placenta, enter meninges, and invade GI tract depends on what?
interaction of internalin and E-cadherin on those tissues
After entering a cell Listeria produces:
listeriolysin O along with phospholipases which allow it to escape from the phagosome in the cytoplasm
•LLO: main virulence factor. Induces T cell receptor unresponsiveness, interferes with host immune response
In the host cell cytoplasm bacterial surface proteins bind to host cell cytoskeletal proteins and induce actin polymerization which generates sufficient force to propel the bacteria into adjacent, uninfected host cells.
•Form “rocket tails” via actin polymerization
Listeria is a facultative intracellular pathogen, so those with defects in cell-mediated immunity such as those with reduced numbers of CD4 lymphocytes are at increased risk for listeriosis. Cytokine activation of macrophages (by interferon gamma) is necessary to kill the organism
How is Listeria transmitted?
-organism is distributed in animals, plants, and soil and is transmitted to humans primarily by ingestion of unpasteurized milk products (milk and cheese!) (it can survive in the frig), undercooked meat, and raw veggies
Pregnant women: no soft cheeses, no cold deli meat/hot dogs
What diseases does listeria cause in immunocompetent pts?
gastroenteritis characterized by watery diarrhea, fever, HA, myalgias, and abdominal cramps
Listeria account for less than 1 percent of reported cases of bacterial foodborne infections. Requires large inoculum. Usually lasts 2 days or less.
What diseases does listeria cause in pregnant pts?
Asymptomatic or mild influenza-like illness (3rd trimester) (Fetal death and premature birth can also occur due to maternal infection.)
Listeria has a predilection for the placenta and the central nervous system. How this occurs is not well understood. Listeria crosses the placenta during maternal bacteremia and infects the fetus.
What diseases does listeria cause in neonates, immunocompromsied, and elderly pts?
Sepsis and/or meningoencephalitis (most common CNS infection
57 adults who ingested contaminated cheese: 21 percent had bacteremia, 40 percent had meningitis, and 39 percent had meningoencephalitis [7]. Forty-two percent had an underlying disease, and more than one-half were at least 65 years of age
How does listeria meningoencephalitis present?
–Mild illness with fever and mental status changes
–Can have fulminant course with coma
–Most adults have a subacute illness; almost half present without signs of meningeal irritation
How is listeria meningoencephalitis diagnosed?
–In subacute presentation, CSF can look like TB or fungal: Lymphocytic predominant, elevated protein, low glucose.
–CSF cultures are usually positive
How is listeria meningoencephalitis tx?
–Ampicillin/Penicillin +/- gentamicin
–Alternative for PCN allergy: Bactrim
Describe Haemophilis influenzae
•Small gram negative bacillus (coccobacillary rod) with polysaccharide capsule (not all strains are encapsulated)
–6 serotypes based on antigenicity of capsule; B is the most important
–Other nonencapsulated strains considered nontypable (cause upper and lower resp tract infections)
Describe the pathogenesis of Haemophilis influenzae
–Inhaled into respiratory tract resulting in asymptomatic colonization or infection (sinusitis, otitis media, PNA)
–From respiratory tract can enter bloodstream and spread to the meninges (caused primarily by encapsulated strains)
More about H. influenzae virulence determinants and plating
Also produces endotoxin and IgA protease
Culture on chocolate agar requires factors V (NAD+) and X (hematin) for growth
Who gets H. flu meningitis?
- Exclusively human pathogen
- Most infections occur in children 6 months to 6 years (decline in maternal IgG, also can’t generate sufficient antibody against the capsule until around 2 years)
- Clinically meningitis is indistinguishable from other causes of bacterial meningitis
–Acute onset
How is H. flu meningitis tx?
Ceftriaxone
Is there a vaccine for H. flu?
•Hib conjugate vaccine
Give to All infants: 2-3 doses 6 weeks to 6 months old; Booster at 12-15 months
What are the common outcomes of bacterial meningitis?
- 10-30% mortality even with appropriate treatment in high-income countries (Meningitis due to S. pneumoniae 19-37% case fatality rates)
- 30% of survivors have long-term neurologic sequelae (hearing loss, other focal deficits)
–Meningococcal meningitis 3-13% case fatality rate with morbidity rates of 3-7%
What are some risk factors for a poor outcome with meningitis?
Systemic compromise, older age, impaired consciousness, low white count in CSF, and low platelet count
