Antifunals

Question 1

Amphotericin B Mechanism

Answer 1

Binds ergosterol - disrupts wall function and creates small pores.

Question 2

Echinocandin Mechanism

Answer 2

Inhibits B-(1,3)-glucan synthase

• Responsible for cross-linking
• Required for cell wall synthesis

Question 3

Azole Mechanism

Answer 3

Inhibits Cytochrome P450 lanosterol 14-a demethylase

- Required for ergosterol biosynthesis

Question 4

Amphotericin B Toxicities

Answer 4

“Shake and bake”
Nephrotoxicity
- Renal artery vasoconstriction
- Binds to renal tissues

Question 5

Advantages of LFAB ( FWAB or Bacontericin B)

Answer 5

Delays delivery to kidney due to lipophilicity.

Question 6

Agents - Cidal or static?

Answer 6

Ampho - cidal
Azole - static
Echino - cidal against Candida

Question 7

Major drug interaction with Azoles

Answer 7

They inhibit CYP enzymes - 3A4!

Also, PGP

Question 8

Low end of Fluconazole dose

Answer 8

6-12 mg/kg/day in the ICU

Question 9

Fluconazole Strengths

Answer 9

C. albicans

Question 10

Fluconazole weaknesses

Answer 10

Does not cover molds

Often under dosed

Question 11

Voriconazole strengths

Answer 11

Broad spectrum

• Candida
• Aspergillus *
• NOT Mucorales or Zygomycetes

IV and PO
Generic

Question 12

Gold standard for Aspergillus

Answer 12

Voriconazole

Question 13

Voriconazole weaknesses

Answer 13

Metabolite and cancer risk
Dosing strategy concerns
Toxicities
- LFT increases
- Hallucinations

Question 14

Posaconazole strengths

Answer 14

Broadest spectrum

• Candida
• Aspergillus
• Zygomycetes

IV and delayed release tablet have reliable PK
- QD as oral

Question 15

Posaconazole weaknesses

Answer 15

Very expensive

Question 16

Isavuconazole (Cresemba) strengths

Answer 16

Decent spectrum

• Aspergillus
• Mucorales (limited data)
• NO CANDIDA

IV and oral

• QD as oral
• IV : no cyclodextrin (accum. in renal failure)

Question 17

Isavuconazole weaknesses

Answer 17

No prophylaxis data

Very long t1/2 - IV needs loading dose

Question 18

“Advanced” Azole Indications

Answer 18

Voriconazole - TREATMENT of IA and IC
Posaconazole - PROPHYLAXIS in high risk patients
Isavuconazole - TREATMENT of IA & Mucormycosis

Question 19

Echinocandins include

Answer 19

“Whatever-a-fungin”

Question 20

Echinocandin strengths

Answer 20

Potent against Candida (cidal)
Really well tolerated
Great PK
Few interactions
No cross-resistance with Azoles

Question 21

Echinocandin weaknesses

Answer 21

Limited spectrum: Candida >>> Aspergillus (combo)
- That's about it.
- Not C. neoformans
No oral form
High cost

Question 22

Flucytosine (5-FC)

Answer 22

Think Cryptococcal meningitis

Question 23

Terbinafine

Answer 23

Toe nails

Question 24

Greatest risk for Invasive Candidiasis

Answer 24

GI-Perforation
Also being in the ICU > 3 days
- Really when you have something put inside you.

Question 25

Increasingly prevalent Candida species resistant to fluconazole:

Answer 25

C. glabrata

Question 26

Candida species completely resistant to fluconazole:

Answer 26

C. krusei

Question 27

What to use for C. krusei

Answer 27

Echinocandins: Whatever-a-fungin | Maybe Vori or Posa

Question 28

Only candida species with resistance to Echinocandins

Answer 28

C. parapsilosis

Question 29

What to use for C. glabrata

Answer 29

Echinocandinds: Whatever-a-fungin IF resistant to Fluconazole. - If resistant to one azole, resistant to all azoles.

Question 30

Two Candida species that don't show resistance yet:

Answer 30

C. albicans and C. tropicalis

Question 31

Poor prognosis in Candidemia

Answer 31

Older age APACHE > 2 Immunosuppressive therapy C. tropicalis infection (seems weird)

Question 32

Predictors of good outcome from study:

Answer 32

Removal of central venous catheter | Treatment with echinocandin

Question 33

Initial treatment recommendation for Candidemia in non-neutropenic adults:

Answer 33

Echinocandin 1st line or Fluconazole 800mg followed by 400mg

Question 34

What's the deal with Candida auris?

Answer 34

It causes severe illness. It can be resistant to all three antifungal options. It is increasing in prevalence. It is difficult to identify. It is showing up in hospitals and nursing homes.

Question 35

When would you worry about IFI (Aspergillosis)

Answer 35

Severyly immunocomprimised; bone marrow/blood cancer.

Question 36

Common species involved in IFI

Answer 36

A. fumigatus | A. flavus

Question 37

Where do you see IFI show up?

Answer 37

Lung and sinuses mostly | CNS most common secondary site

Question 38

Treatment for IFI

Answer 38

Voriconazole - isavu and posa probably work too - addition of Echinocandin may be seen in future - Isavu less SE's Alternative: Lipid-AmpB

Question 39

What do you do if someone gets a mold infection while on an Azole

Answer 39

Ampho

Question 40

Prophylaxis for IA

Answer 40

Posa > Vori > micafungin

Question 41

Therapeutic drug monitoring for Voriconazole:

Answer 41

Stay above: 2 | Stay below: 5-6