Exam #7: Bacterial Infections of the CNS

Question 1

What are the two categories that CNS infections are divided into?

Answer 1

Meningitis= infections of the meninges

Encephalitis= infections of the brain parenchyma itself

Question 2

What must microbes disrupt to gain access to the CNS?

Answer 2

BBB

Question 3

What is hematogenous spread?

Answer 3

Spread through the bloodstream e.g. bacteremia

Question 4

What are the different modes of entry to the CNS?

Answer 4

1) Hematogenous spread
2) Spread from an adjacent site
3) Direct inoculation (rare)
4) Neuronal spread e.g. HSV

Question 5

What is acute pyogenic meningitis?

Answer 5

Bacterial meningitis that leads to the proliferation of neutrophils

Question 6

What is aseptic meningitis?

Answer 6

Viral meningitis (historical term, meningeal inflammation without growth on culture)

Question 7

How does bacterial meningitis compare to viral meningitis?

Answer 7

Bacterial is generally more severe

Question 8

Who is predisposed to get meningitis?

Answer 8

Pneumococcal meningitis:
- Pneumonia & chronic OM

Meningococcal meningitis:

• 10-20 % population are carriers
• History of recent UTI–>easier to get into the CNS
• MAC (terminal) Complement deficiencies
• Outbreaks are most common in winter

Generally, individuals with altered or underdeveloped immune status are at an increased risk of developing bacterial meningitis

Question 9

What are the common virulence factors associated with bacterial pathogens that cause CNS infections?

Answer 9

• Capsules= anti-phagocytic

- Fimbriae, pilli, & outer membrane= function in attachment & colonization

Question 10

Describe the general pathophysiology of meningitis.

Answer 10

1) Bacterial penetration of the BBB

2) Inflammatory reaction*
- Many of the clinical manifestations are a result of the immune response in the confined area of the brain

3) Cell wall & toxin components of bacteria exacerbate the inflammatory response
- IL-1 & TNF-a –>ICP, Altered cerebral blood flow, Cerebral edema

Question 11

What symptoms are characteristic of meningitis?

Answer 11

Fever
Headache
Stiff neck (nuchal rigidity)

• AMS

Question 12

What CSF abnormalities are associated with bacterial meningitis?

Answer 12

*Presence of PMNs
Decreased glucose
Increased protein
Increased pressure

Question 13

What CSF abnormalities are associated with viral meningitis & encephalitis?

Answer 13

Mono/lympho
*Rare PMN
Normal glucose
Normal or slight increased protein & pressure

Question 14

What is the approach to empirical treatment of suspected CNS infection?

Answer 14

1) Empirical abx therapy is generally initiated
2) Age, predisposing factors, and other symptoms may provide clues
3) Examination of CSF & results should direct treatment plan

Question 15

Who is most commonly infected with bacterial meningitis?

Answer 15

Infants & children

Question 16

What are the MOST common etiological agents that cause bacterial meningitis in children?

Answer 16

Listen in order:

S. pneumoniae
N. meningitides 
Group B step. 
Listeria monocytogenes 
Haemophilus influenzae

Question 17

What is the most common cause of bacterial meningitis in neonates (<1 month)?

Answer 17

Group B Strep (S. agalacticae)

Note that this is especially common in kids that are less than 2 months old

Question 18

What pathogen becomes increasingly prevalent in the teenage years?

Answer 18

N. meningitidis

Question 19

What pathogen becomes more prevalent in the very young & old?

Answer 19

Listeria monocytogenes

Question 20

List the characteristics of S. pneumoniae.

Answer 20

Gram positive coccus
Catalase neg 
Chains
Diplococci 
Oval 
a-hemolytic 
Optochin sensitive 

Capsulated

Question 21

What is the most common cause of vaccine preventable death in the US?

Answer 21

Pneumococcal disease

Question 22

What clinical syndromes may pneumococcal meningitis follow?

Answer 22

Pneumonia

OM

Question 23

List the virulence factors associated with S. pneumoniae.

Answer 23

Capsule
Pneumolysin= kills WBC
IgA protease

Question 24

Describe the course of pneumococcal meningitis infection.

Answer 24

Acute onset
High mortality
Neurological sequela

Question 25

How is pneumococcal meningitis diagnosed?

Answer 25

Clinically - Gram stain CSF - Latex agglutination - Standard culture....etc.

Question 26

How is pneumococcal meningitis treated?

Answer 26

*Medical emergency, begin empirical abx therapy with vancomycin & a cephalosporin*

Question 27

How is pneumococcal meningitis prevented?

Answer 27

Vaccination; however, note that there are 90 different capsular polysaccharides - Not ALL are covered - However, currently we have a varieties of polysaccharide vaccines

Question 28

What is PPV23 & what is the problem with PPV23?

Answer 28

This is the 23 valent vaccine for S. pneumonia that came out in the 1980s--DOESN'T work well in young kids

Question 29

What are the current vaccine recommendations for S. pneumoniae

Answer 29

- Recommended for kids >2 with chronic illness, immunosuppression, & other risk factors - Also recommended for adults >65

Question 30

What is PCV13?

Answer 30

Pneumococcal polysaccharide conjugated nontoxic diptheria toxin - 13 serotypes

Question 31

List the characteristics of Neisseria meningitidis.

Answer 31

``` Gram - diplococcus Kidney bean appearance Oxidase positive Catalase positive Capsule LOS ```

Question 32

How does LOS differ from LPS?

Answer 32

- Shorter side chains | - No repeating polysaccharide

Question 33

How is Neisseria meningitis cultured?

Answer 33

CO2 supplementation

Question 34

What infections does Neisseria meningitis cause?

Answer 34

``` Meningitis Bacteremia Pneumonia Arthritis OM Epiglotittis ```

Question 35

How is Neisseria meningitis transmitted?

Answer 35

Aerosolized droplets

Question 36

What are the clinical features of Neisseria meningitis infection? How does meningcococcal meningitis differ from pneumococcal meningitis?

Answer 36

Neisseria meningitis presents as: - Abrupt onset fever - Headache - Neck pain i. e. as typical meningitis However, meningococcal meningitits also is accompanied by: * Rash - hypotension - multi-organ failure

Question 37

What causes the rash seen in Neisseria meningitis infection?

Answer 37

Antibody complexes

Question 38

How is Neisseria meningitis treated?

Answer 38

Vancomycin and/or a cephalosporin followed by once N. meningitidis is identified PCN

Question 39

How is meningococcal meningitis prevented?

Answer 39

Vaccination Serotypes A, C, Y, W-135, BUT NOT B

Question 40

What serotype causes half of the meningococcal meningitis causes in children under 2? Is there a vaccine for this strain?

Answer 40

- Serotype B | - No

Question 41

How is meningococcal meningitis diagnosed?

Answer 41

- Recognize clinical signs & symptoms - Gram stain CSF - Rapid antigen detection in CSF

Question 42

Describe the current meningococcal vaccine that is used in clinical practice.

Answer 42

"MCV4" -Meningococcal Conjugate Vaccine Tetravalent polysaccharide conjugate vaccine

Question 43

List the characteristics of Streptococcus agalactiae.

Answer 43

``` Gram + cocci Chains Catalase negative B-hemolytic Group B ```

Question 44

What patient population is most susceptible to GBS meningitis?

Answer 44

Newborns

Question 45

What other infections are caused by GBS?

Answer 45

Sepsis UTI Soft tissue infections

Question 46

Why is the neonate susceptible to GBS infection?

Answer 46

- 10-30% of pregnant women are colonized by GBS - Thus, maternal intrapartum GBS colonization is a MAJOR risk factor for the development of early onset disease in infants *Note that maternal colonization increases risk of infection x25

Question 47

What virulence factors are associated with GBS?

Answer 47

Polysaccharide capsule

Question 48

Aside from maternal GBS colonization, what else increases the risk of GBS meningitis in the neonate?

Answer 48

- Obstetric issue - GBS bacteuria - Previous infant with GBS infection - African American - Low GBS antibody

Question 49

What are the characteristics of early onset GBS disease?

Answer 49

Early onset= within the first week of life Disease is characterized by bacteremia, pneumonia, & meningitis - Respiratory distress - Labored breathing - Fever - Lethargy - Irritability *Note that 1/4 that survive will suffer from permanent neurological sequela

Question 50

What are the characteristics of late onset GBS disease?

Answer 50

Late onset= between 1-3 weeks after birth Similar signs and symptoms of "early onset," but meningitis is more common

Question 51

How is GBS diagnosed in the neonate?

Answer 51

- Recognition of clinical signs and the identification of the organisms--FEVER in NEONATE is a BIG DEAL - Identification of organism in CSF - Serologic confirmation by presence of Group B antigen

Question 52

How is GBS treated?

Answer 52

PCN

Question 53

How is neonatal GBS prevented?

Answer 53

- Universal screening of all pregnant women - Intrapartum antibiotics i.e. high doses of IV PCN ~4 hours prior to delivery *Note that there is no vaccine to prevent GBS

Question 54

List the characteristics of Haemophilus influenzae type B.

Answer 54

Gram negative rod Requires X & V Chocolate agar Encapsulated

Question 55

What serotype of Haemophilus influenzae causes meningitis?

Answer 55

Type B

Question 56

Is there a vaccine for HiB?

Answer 56

Yes, (conjugated) vaccine against the poly-ribitol phosphate (PRP) capsule

Question 57

What diseases are caused by non-encapsulated Haemophilus influenzae?

Answer 57

Pinkeye OM Sinusitis

Question 58

What diseases are caused by encapsulated Haemophilus influenzae?

Answer 58

Meningitis | Epiglottitis

Question 59

What is the major neurological sequelae from HiB meningitis?

Answer 59

Hearing loss

Question 60

How is HiB diagnosed?

Answer 60

Gram stain CSF | Latex agglutination test

Question 61

How is HiB treated?

Answer 61

Similar to other forms of bacterial meningitis--broad to narrow spectrum

Question 62

List the characteristics of Clostridium tetani.

Answer 62

- Gram + rod - Anaerobic - Spore forming--soil & feces - Neurotoxin--tetanospasmin

Question 63

Describe the typical entrance mechanism of Clostridium tetani.

Answer 63

- Spores enter through wound contamination or traumatic inoculation - Umbilical stump can be contaminated in neonatal tetanus

Question 64

What is tetanospasmin? Describe the mechanism of action.

Answer 64

- AB tetanus toxin - B binds to motor neurons via polysaialoganglioside receptors - Entire toxin is internalized & retrogradely transported to the spinal cord - In the spinal cord, it activates the release of GABA - Leads to "SPASTIC PARALYSIS"

Question 65

What are the symptoms of tetanus?

Answer 65

Descending pattern of symptoms as follows: "Lock jaw" Neck stiffness Difficulty swallowing Muscle rigidity

Question 66

How is Tetanus diagnosed?

Answer 66

Mostly based on clinical presentation & exposure history

Question 67

How is Tetanus treated?

Answer 67

Passive & active immunization - Administer Ig - Vaccinate with inactivated tetanus toxin

Question 68

How is Tetanus prevented?

Answer 68

Vaccination with tetanus toxoid--the "T' in DTaP *formalin inactivated tetanus toxin*

Question 69

List the characteristics of Clostridium botulinum.

Answer 69

Gram positive rod Anaerobic Spore forming Produce neurotoxin

Question 70

What is Infant Botulism?

Answer 70

"Floppy baby" Sydrome - Infants ingest honey containing spores & produce toxin - Most common cause of Botulism in the US

Question 71

List the characteristics of Listeria monocytogenes.

Answer 71

Gram + rod | Motile

Question 72

What is Listeria monocytogenes associated with?

Answer 72

Consumption of contaminated food i.e. deli meat, milk, cheese, poultry *Transplacental transmission to neonate

Question 73

How does Mycobacterium tuberculosis compare to other bacterial meningitis infections? What diseases can it cause?

Answer 73

Chronic symptom onset - Meningitis - Brain abscess

Question 74

What CNS infections can S. aureus cause?

Answer 74

Meningitis | Brain abscess