Antibiotics

Question 1

What is the MOA of Amphotericin B?

Answer 1

Complexes with ergosterol to disrupt fungal cell membrane.

However, builds resistance to alteration to ergosterol

Given via IV

Question 2

What does Amphotericin B cover against?

Answer 2

Spectrum of activity: very broad
Yeasts: Candida albicans, cryptococcal neoformans
Organism causing endemic mycoses: histoplamsa capsulatum, blastomyces dermatitidis, Coccidioides immitis
pathogenic molds: aspergillosis fumigatus, agents of mucormycosis

Question 3

What are the adverse side effects of Amphotericin B?

Answer 3

Most common:
—immediate reactions: fever, chill.s muscle spasms, vomiting, headache, and hypotension
Long term:
—renal toxicity

Question 4

What is the MOA of Flucytosine?

Answer 4

MOA: converted to 5-flyorodeoxyuridine monophosphate (FdUMP) and fluorouridine triphosphate (FUTP), which inhibits DNA and RNA synthesis, respectively

Resistant: altered drug metabolism

Question 5

What is the spectrum of activity of Flucytosine?

Answer 5

Narrow,
C. Neoformans
Some candida spp.

Question 6

What are the adverse effects of Flucytosine?

Answer 6

Anemia, leukopenia, thrombocytopenia

Question 7

What are the MOA of azoles?

Answer 7

Inhibition of fungal CYP450 enzymes

Resistance: up regulation of fungal CYP450

Question 8

What is the spectrum of activity of azoles?

Answer 8

Broad spectrum

Due to individual drugs

Question 9

What are the adverse effects of azoles?

Answer 9

Relatively non-toxic
Minor GI issues
Abnormalities in liver enzymes

Question 10

What is Ketoconzole MOA?

Answer 10

Greater propensity to inhibit mammalian CYP450

Question 11

Describe Itraconazole?

Answer 11

Oral and IV formulation
Potent antifungal activity
Poor penetration into cerebral spinal fluid
Works against:
-dimorphism fungi: histoplasmosis, blastomyces, and sporothrix
-aspergillosis spp: largely replace by voriconzole as the azole of choice tho
-dermatohpytoses and onychomycosis

Question 12

Describe Fluconazole?

Answer 12

IV and oral formulation
Inhibitor of the mammalian CYP3A4
Visual disturbances are common (30%) 
Spectrum:
-similar to itraconazole 
-Candida spp. And the dimorphism fungi 
-Rx for choice for invasive aspergillosis and some envirnmomental molds-enhanced activity against aspergillosis spp versus the azoles

Question 13

Describe posaconazole?

Answer 13

Available only as a liquid oral preparation
Spectrum:
-broadest spectrum member of the azoles
-Activity against most species of candida and aspergillosis
-activity against mucormycosis
Currently licensed for:
-salvage therapy in invasive aspergillosis
- prophylaxis infections during induction Chemotherapy for leukemia
Allogeneic bone marrow transplant pt w/ graft-vs-host disease

Question 14

What are the echinocandins?

Answer 14

Caspofungin
Micafungin
Andulafungin

Question 15

What is the MOA of echincandins?

Answer 15

Large cyclic peptides linked to a long-chain fatty acids

MOA: inhibit glucagon synthase

Question 16

What are the spectrum of activity of echinocandins?

Answer 16

Candida
Aspergillosis
Or C. Neoformans or the agents of zygomycosis and mucormycosis
Licensed for:
-disseminated and mucocutaneous candida infections
-empiric antifungal therapy during febrile neutropenia (replacing Amphotericin B)

Question 17

How do species resist echinocandins?

Answer 17

Point mutations in glucan synthase

Question 18

Describe Caspofungin?

Answer 18

Specific spectrum:
-invasive aspergillosis
—only as a salvage therapy in pt that don’t respond to Amphotericin B
—not primary tx

Halftime-life= 9-11 hrs

Question 19

Describe Micafungin.

Answer 19

Specific spectrum:

• mucocutaneous candidiasis
• candidemia
• prophylaxis of candidal infection in bone marrow transplant pt

Half-life:11-15 hrs

Question 20

Describe Anidulafungin.

Answer 20

Specific Spectrum:
-esophageal candidiasis and invasive candidiasis, including candidemia

Half-life= 24-48 hrs