PHARM - CNS Infections

Question 1

qwhat are the community aquired etiologies of meningitis in an immunocompetent patient ?

Answer 1

• s. pneumonia
• n. meningitis
• h. influenza
• listernia monocytogenes > 50

Question 2

what are the community acquired etiologies of meningitis in an immunocompromised patient ?

Answer 2

• listeria monocytogenes
• psueodmonas aeurginosa

Question 3

tx of community aqcuired meningitis in a

• immunocompetent patient?
• immunocompromised patient?

Answer 3

immunocompetent: combination of

• vancomycin
• ceftriaxone / ceftaxomine (3rd gen ceph)
• +/- ampicillin: only if > 50

​immunocompromised: combination of

• vacomycin
• ampicillin
• either: ceftaxadime / cefepime (4th gen cehps) OR meropenum

Question 4

tx of healthcare associated meningitis?

Answer 4

same as community acquired in a I/C patient.

combination of

• vacomycin
• ampicillin
• either
  
  • ceftaxadime / cefepime (4th gen cehps)
  • meropenum

Question 5

tx of healthcare associated meningitis?

Answer 5

same as community acquired in a I/C patient.

combination of

• vacomycin
• ampicillin
• either
  
  • ceftaxadime / cefepime (4th gen cehps)
  • meropenum

Question 6

tx of penetrating head wound meningitis?

Answer 6

same as community acquired in a I/C patient.

combination of

• vacomycin
• ampicillin
• either
  
  • ceftaxadime / cefepime (4th gen cehps)
  • meropenum

Question 7

tx of meninigits in children?

Answer 7

same as tx for community acquired meninigits in immunocompetent patients

combination of:

• vancomycin
• ceftriaxone / ceftaxomine (3rd gen ceph)
• +/- ampicillin: if under 3 yeares

Question 8

in the treatment of meingitis, what can be used to replace the cephalosporins in a pt with a beta lactam allergy?

Answer 8

• community associated - moxifloxacin
• I/C, healthcare associated, penetrating wound - aztreonam, ciproflaxacin
• children - aztreonam or chloramphenicol

Question 9

in the treatment of meningitis, what can be used to replace the ampicillin in a pt with a beta lactam allergy?

Answer 9

TMX

Question 10

why can impenem not be used to treat meningitis?

Answer 10

blocks GABAa receptors & thus poses too high of a seizure risk

Question 11

what is the difficultly with using beta lactamases to treat meningitis?

Answer 11

• patient can develop resistance (i.e., their cells produce beta lactamase)
• beta-lactamase inhibitors are not an effective solution becauase of their minimal CNS penetration

Question 12

how are beta-lactams eliminated?

Answer 12

by organic acid transporters (OAT) 1 & 3 in the kidney, except for three excreted by the liver:

nacillin, oxacillin, and ceftriaxone

Question 13

how is probenacid related to beta-lactam use?

Answer 13

probenacid inhibitrs tubular transport by OAT in the kidney. thus, it it increases plasma levels of all beta-lactams except those that are excreted via the liver: nafcillin, oxacillin, ceftriaxone

Question 14

nafcillin is a potent inducer of…?

Answer 14

CYP-3A4

Question 15

what is the role of ampicillin in the treatment of meningitis

Answer 15

covers listeria monocytogenes. used in

• community associated > 50
• I/C community associated
• healthcare associated
• penetrating headwound
• children < 3

Question 16

whare the roles of cephalosporins in the treatment of meningitis?

Answer 16

• 3rd: ceftriaxone, ceftaxomine used in
  
  • community acquired
  • in children
• 4rd: cefepime, ceftaxidime: covers psueodmonas & can thus be used in
  
  • community acquired - I/C
  • healthcare associated

Question 17

what is the role of the carbapenems in the treatment of meningitis?

Answer 17

meropenem covers pseudomonas (& double covers literia), and can thus be in combo therapy for:

• community acquired meningitis in I/C patient
• healthcare associated meningitis

imipenem is NOT an alternative b/c of its seizure risk

Question 18

what is the role of aztreonam in the treatment of meningitis

Answer 18

to replace cephalosporins for patients with beta lactam allergies

Question 19

aztreonam - relevant properties

Answer 19

• only B-lactam with no gram positive coverage
• not resistant to ESBL
• excreted renally but NOT affected by probenaci
• AE: thrombocytopenia, neutropenia

Question 20

what is the role of vancomycin in the treatment of meningitis?

Answer 20

to double cover s. pneumonia (vanc = gram + only)

note that it does not cover listeria - which is why we add in ampicillin in I/C, healthcare, wound-associated meningitis

(used in all regimens)

Question 21

vancomycin - AEs

Answer 21

• “red man syndrome” - erythema in response to histamine release
• nephrotoxicity

Question 22

vancomycin should be monitored when used with what other Abx?

why?

Answer 22

aminoglycosides

they are also nephrotoxic

Question 23

what is the role of chloramphenicol in the teatment of meningitis?

Answer 23

can be used to replace the cephalosporins in children with a B-lactam allergy

Question 24

chloramphenicol

• coverage
• MOA
• PK
• AE

Answer 24

• coverage: gram + and gram - but not psuedomonas
• MOA: binds 50s subunit inhibiting peptidyl transferase
• PK: metabolized by glucaronidation
• AE
  
  • anemia
  • aplastic anemia
  • gray baby syndrome - in infants w/ no glucuronidation enzyme
    
    • cyanosis + CV collapse

Question 25

what is the role of linezolid in the treatment of meningitis?

Answer 25

to replace vancomyin

note - however - that is it only bacteriostatic, not bacteriocidal

Question 26

linezolid

• MOA
• AEs

Answer 26

• MOA: binds 50s subunit and prevents it from complexes with 30s
• AEs:
  
  • bone marrow suppresion
  • SEVERE HTN - esp if given with MAO inhibitors
  • serotonin syndrome - fever, agititation, mental status changes

Question 27

TMP-SMX

• MOA
• AEs

Answer 27

• MOA: inhibits folic acid pathway
• AEs:
  
  • hypersensitivity
  • anemia
    
    • hemolytic - in pts w/ G-6-P deficiency
    • megoblastic
  • stevens-john syndrome: rash
  • in preganncy: kernicterus / jaundice - induced brain damage
• C/I: caution in 1st trimester