Systemic Antifungals

Question 1

Amphotericin B

Answer 1

IND: Systemic fungal infections. Drug of choice and most effective agent for systemic mycoses, but highly toxic; reserved for progressive and potentially fatal system fungal infections
MOA: Binds to fungal cell membrane and increases permeability, allows for leakage of intracellular ions which reduces viability
BOX: n/a
CON: n/a
ADR: Not well tolerated. Amphoterrible

Question 2

Azole antifungals

Answer 2

Broad spectrum antifungal alternative to Amphotericin B.
Low toxicity, oral formula available.
INHIBIT CYP enzymes and can increase the levels of many other drugs
MOA: Inhibit the synthesis of ergosterol; an essential part of the cytoplasmic membrane

Question 3

Fluconazole

Answer 3

IND: COCCIDIOMYCOSIS, Candidiasis, cryptococcal meningitis
MOA: azole
BOX: n/a
CON: CYP 3A4 substrates
ADR: QT prolongation, Torsades. Derm rxns; SJS TEN

Question 4

Itraconazole

Answer 4

IND: HISTOPLASMOSIS, COCCIDIOMYCOSIS, Aspergillosis, blastomycosis, candidiasis, onychomycosis
MOA: azole
BOX: CHF, cause or exacerbate. Avoid in pts with CHF or Hx of CHF.
Drug interactions
CON: Pregnancy, CHF, drug interactions
ADR: GI
Oral suspension: food decreases absorption. Caps: food increases absorption

Question 5

Posaconazole

Answer 5

IND: Invasive aspergillosis, candidiasis, etc
MOA: azole
BOX: n/a
CON: CYP substrates
ADR: QT prolongation. GI

Question 6

Voriconazole

Answer 6

IND: Treatment of fungal infections. “workhorse for non-candidiasis” Aspergillosis first line.
MOA: azole
BOX: n/a
CON: CYP substrates
ADR: Visual disturbances: optic neuritis, vision color changes, episcleritis and scleritis, audio and visual hallucinations. Hepatotoxicity

Question 7

Isavuconazole/Isavuconazonium Sulfate

Answer 7

IND: Aspergillosis, mucomycosis. Combat some resistances
MOA: IS is a Prodrug that is rapidly hydrolyzed to active isavuconazole in the blood. Then just azole
BOX: n/a
CON: CYP substrates, familial short QT syndrome
ADR: Hepatotoxicity. GI

Question 8

Echinocandins

Answer 8

IND: Invasive aspergillosis, candidemia, other candida infections
MOA: Inhibits synthesis of beta 1,3 D Glucan; an essential part of cell wall of fungi. More static than other agents
BOX: n/a
CON:
ADR: Infusion related rxns.
Names are -fungin

Question 9

Aspergillosis

Answer 9

Invasive aspergillosis MC presents as invasive pulm aspergillosis, can occur in other organs.
Voriconazole IV or PO is 1st line, others used if it isn’t tolerated. Posaconazole and Isavuconazole.
Severe invasive, in a severely immunocompromised pt: Voriconazole AND an echinocandin
Amphotericin B reserved for treatment resistant or severe cases prior to ID’ing aspergillosis

Question 10

Histoplasmosis

Answer 10

MC in midwest states.
Most cases are self-limiting and require no therapy
If it progresses, we use Itraconazole (most effective/1st line)
Severe/life threatening: Amphotericin B for 1-2wks before switching to Itrazonazole

Question 11

Coccidiomycosis

Answer 11

Pulmonary infection
US southwest
Immunocompetent/ no risk factors: nothing
Competent w/risk factors: Fluconazole 400mg daily or Itraconazole 200mg BID x 6-12wks.
Compromised mild-moderate: Fluconazole 400mg daily or Itraconazole
Compromised severe: Fluconazole or Itraconazole

Question 12

Candidiasis

Answer 12

Some species are resistant to Fluconazole and other Azoles. (Glabrata or Krusei)
Fluconazole is 1st line if it isn’t one that commonly has a resistance
Empiric therapy: Start with Echinocandin until cultures are narrowed to the specific Candida species