Meningitis - A. Prunuske

Question 1

Meningitis develops in the __________ …

Answer 1

subarachnoid space, which lacks antibody and complement production required for phagocytosis

Question 2

This type of meningitis has the highest incidence during first year of life

Answer 2

Aseptic Meningitis Syndrome (often Viral but could be noninfectious)

Fever, headache, and photophobia
less neck stiffness and altered mental status

CSF increase in lymphocytes and monocytes, slight increase in protein, and normal glucose.

Question 3

enteroviruses and meningitis

Answer 3

>85% of viral meningitis cases include enteroviruses

coxsackievirus, echovirus, human enteroviruses 68-71

common in late summer and fall

Question 4

Are enteroviruses DNA or RNA viruses? What else to you know?

Answer 4

(+) ssRNA

fecal to oral

Capsid symmetry
Icosahedral

No Envelope (Naked)

Question 5

A patient presents with fever, stiff neck, irritability, and neurologic dysfunction.

Symptomes appeared with acute onset and progression.

Meningeal inflammation associated with inflammatory exudate in the CSF containing many polymorphonuclear leukocytes, increased protein, and decreased glucose

Answer 5

**Bacterial meningitis –> Septic meningitis **

Life-threating and requires prompt empiric therapy prior to lumbar puncture.

Order of treatment: blood culture first, then antibiotic (ceftriaxone + …), then lumbar puncture (if safe)

Question 6

Bacterial meningitis treatment:

MRSA, resistant strep

Answer 6

**ceftriaxone + vancomycin **

Question 7

Bacterial meningitis treatment:

HSV

Answer 7

ceftriaxone + acyclovir

Question 8

Bacterial meningitis treatment

Pseudomonas, AIDS

Answer 8

ceftriaxone + cefepime

Question 9

Bacterial meningitis treatment:

Listeria

Answer 9

**ceftriaxone + ampicillin **

Question 10

ceftriaxone mechanism of action

Answer 10

Beta-lactam: Binds PBPs, inhibiting the transpeptidation step in peptidoglycan synthesis which is required for bacterial cell walls

Used for streptococci and more serious Gram- infections, Can cross blood brain barrier

Resistance: inactivation of the drug by beta-lactamases

Side effects: **Strong association with Clostridium difficile- associated diarrhea **

Question 11

What is the most common bacterial meningitis in adults?

What is the most common in 11-17 year olds?

How about infants less than two months?

Answer 11

**Streptococcus pneumonia **

Neisseria meningiditis

GBS

Question 12

Neisseria meningiditis

Answer 12

Meningococcal meningitis; Gram negative, diplococcus

Virulence factors include pili, IgA protease, capsule, and endotoxin

Transmit through respiratory droplets

Definitive and prophylactic treatment with ceftriaxone

Question 13

Streptococcus pneumonia

Answer 13

Pneumococcal meningitis
** Gram positive diplococci**, lancet shape

secondary to paranasal sinusitis and otitis media

Corticosteroid dexamethasone give prior to antibiotic leads to a reduction in hearing loss and other neurological sequelae in adults

PCN (penicillin)-resistant S. pneumoniae require coverage with vancomycin

Question 14

Hemophilus influenza type b

Answer 14

Gram negative; “Coccoid” rod

occurs in unvaccinated infants and young children

Infection can be followed by hearing loss

Prevention with Hib vaccine

Treatment with ceftriaxone

Question 15

For what other age group, do you see an increased risk
for Listeria monocytogenes?

Why might the risk of infection from the most common
causes be lower in infants?

Answer 15

Over 65 age group or pregnant

Maternal immunity

Question 16

Group B streptococcus (Lancefield group B antigen)
aka Streptococcus agalactiae

Answer 16

Normal GI and genitourinary tract flora

Pregnant women screened with 25% as carriers and given Penicillin G as prophylactic

All pregnant women 35-37 weeks (2 swabs-vaginal and rectal) screened

Treat with IV Penicillin G 5 million units followed by 2.5 million units q 4 H starting at rupture of membranes or start of labor til delivery

Bacitracin resistant, catalase negative

Question 17

Listeria monocytogenes

Answer 17

Gram positive, rod

Immunosuppressed (pregnancy), old, young

Fever, headache, no nuchal rigidity (diarrhea)

Question 18

Escherichia coli K1 strains

Answer 18

Gram negative, rod

K1 capsular polysaccaride prevents fusion with lysosome, LPS,

If expressing beta-lactamase empiric coverage with ceftriaxone may not be sufficient add carbapenem

Question 19

Mycobacterium tuberculosis

Answer 19

chronic meningitis

Gradual onset beginning with a generalized illness.

Treatment with rifampin, isoniazid, pyrazinamide and ethambutol

requires four drugs because of the resistance capabilities

BCG vaccine

Question 20

Cryptococcus neoformans

Answer 20

inhaled as spores and can disseminate hematogenously to CNS in immunocompromised individuals

chronic meningitis

Treatment: Amphotericin + Flucytosine **until culture negative followed by fluconazole for 3-12 months sometimes rest of life. **

Question 21

Amphotericin B

Answer 21

Binds ergosterol creating holes in fungi membrane allowing leakage of electrolytes.

Broad spectrum: systemic fungal infections in immunocompromised. Active against yeast and molds

Distribution: Liposomal crosses blood brain barrier.

TOXIC because binds cholesterol

Resistance: Rare, decrease ergosterol in membrane

Question 22

Flucytosine (5-FC)

Answer 22

antimetabolite. converted to 5-fluorouracil in fungi, interfering with DNA and RNA syntheses

• *Narrow spectrum**: Yeast (not dimorphic or molds)
• *Candida Albicans** and Cryptococcus

Toxicity: Bone marrow suppression

Resistance: Loss of converting enzyme or transporters, cotreat with amphotericin B to minimize development of resistance and to increase uptake

Question 23

Azoles- Fluconazole (CNS), Itraconazole, Voriconazole(CNS)

Answer 23

binds fungal P-450 enzyme blocks production of ergosterol

Systemic mycoses (dimorphic fungi) and yeast

Toxicity: Drug-Drug interactions, hepatotoxicity, neurotoxicity, alters hormone synthesis- avoid during pregnancy.

Resistance: Altered cytochrome P-450, Upregulation of efflux transporters

Question 24

During a 4-week period in August in a rural county in the Midwest, a total of 29 persons (between the ages of 9-15) had a rapid onset of fever, headache, and photophobia. Some patients had diarrhea for a few days preceding the headache and all had been recently swimming. WBC 54/ul; glucose 65 mg/dL; protein 30 mg/dL

Which of the following is the most likely causative agent?

Answer 24

Echovirus type 9

Question 25

A 3-year-old female presented with one-day history of fever, headache, lethargy, irritability, apnea, and projectile vomiting (over the past 18 hours). Physical examination revealed an irritable febrile child with resistance to being touched or moved; no focal neurologic signs; no cranial nerve deficits. The child’s immunization history was questionable. The CSF examination revealed 2500 WBCs/ul with 78% PMNs; glucose 21 mg/dL; protein 220 mg/dL. Cultures of CSF and blood yielded a Gram – rod capable of growth on chocolate agar, but not on blood agar.

Answer 25

Haemophilus influenzae type B

Question 26

A 3-week-old baby boy was brought to the emergency department with a 24-hour history of fever, poor feeding, irritability, and a seizure that occurred just before arriving at the ED. He was born premature (32 weeks’ gestation) with very low birth weight after a normal vaginal delivery

Which of the following organisms is most likely?

Answer 26

Streptococcus agalactiae

Question 27

A 66-year-old woman was brought to the emergency department with 5 days of fever, headache, and confusion. She had had diarrhea for 2 days that resolved a few days before her current symptoms began. She had a history of rheumatoid arthritis, for which she had been taking prednisone daily for the past several months. The Gram stain of the culture reveals intracellular, Gram-positive rods.

From where might she have contracted the infection?
What is the appropriate treatment?

Answer 27

Listeria monocytogenes

consumption of contaminated food

If at risk, add ampicillin to empiric treatment (ceftriaxone)

Definitive trt: Ampicillin (beta-lactam) + Gentamicin (ribosome inhibitor)

Question 28

Patient with Mycobacterium tuberculosis is advised not to rely solely on oral contraceptives to avoid pregnancy because they may be less effective while she is being maintained on antimycobacterial drugs. The agent most likely to interfere with the action of the oral contraceptive she is taking is…

For which of these drugs, might you need to increase the dose in a for a patient who is a fast acetylater?

Answer 28

Isoniazid

inhibits mycolic acids (component of mycobacterial cell wall). Acetylation by the liver varies genetically and fast acetylators may require higher dose.