Antifungal Drugs*

Question 1

Mechanisms of action of antifungals

 Echinocandins

Answer 1

Mechanisms of action of antifungals

 Echinocandins inhibit glucan synthase, block synthesis of 1‐3 beta glucans in the fungal cell wall.

Question 2

Mechanisms of action of antifungals

 Azoles

Answer 2

Mechanisms of action of antifungals

 Azoles inhibit sterol C‐14 demethylase, block synthesis of sterol

Question 3

Mechanisms of action of antifungals

 Ampho

Answer 3

Mechanisms of action of antifungals

 Ampho damages fungal cytoplasmic membranes

Question 4

Mechanisms of action of antifungals

 Flucytosine

Answer 4

Mechanisms of action of antifungals

 Flucytosine converted to 5FU, inhibits DNA synthesis

Question 5

Amphotericin B resistant:

Answer 5

Amphotericin B resistant:

Scedosporium apiospermum (Pseudallescheria boydii), 
Lomentospora (Sc) prolificans, 
Aspergillus terreus,   
Variable in Candida lusitaniae, 
C. auris

Question 6

Fluconazole resistant:

Answer 6

Fluconazole resistant:

All moulds, 
Candida krusei, 
Candida auris,
Candida haemulonii, 
some Candida glabrata

Question 7

Voriconazole resistant:

Answer 7

Voriconazole resistant:

mucormycosis,
Fusarium solani,
some rare Aspergillus species higher MIC’s: (lentulus, ustus, calidoustus)

Question 8

Echinocandin resistance:

Answer 8

Echinocandin resistance:

Cryptococcus,
Trichosporon,
moulds other than Aspergillus

Question 9

Voriconazole: the fundamentals

Answer 9

Voriconazole: the fundamentals

 Candida, Aspergillus , Scedosporium apiospermum, etc.

 Good CSF levels, none in urine.
 Many drug interactions, hallucinations, hepatitis, photosensitivity, visual changes, peripheral neuropathy
 Many months of Rx: skin cancer, periostitis

Question 10

Voriconazole Periostitis:

Answer 10

Voriconazole Periostitis:

• Bone pain
• Months of Rx
• Alk phos high
• Plasma fluoride high (fluorosis)
• Bone scan
• Exostoses

Question 11

Isavuconazonium/Isavuconazole FYI facts:

Answer 11

Isavuconazonium/Isavuconazole

 Noninferior to vori in invasive aspergillosis.

 No drug in CSF or urine.

 increases cyclosporine, tacrolimus

 Cost= $$$. Teratogenic.

Question 12

Posaconazole, FYI facts

Answer 12

Posaconazole

 Approved for prophylaxis in GVHD or prolonged neutropenia.

 Has been used in mucormycosis once patient has responded to amphotericin B

 Interactions with CYP3A4 increase some drug levels

 Check trough levels.

 Well tolerated.

Question 13

Echinocandins, susceptibility and resistance

Answer 13

Echinocandins

 All Candida species susceptible but resistance can arise during long therapy. Mold activity: Aspergillus

 Resistant: Cryptococcus, Trichosporon

 No drug in urine.

 Protein binding high: poor penetration into CSF and vitreous humor of eye

Question 14

Amphotericin B formulations, FYI facts

Answer 14

Amphotericin B formulations

Penetrate CSF and vitreous humor poorly,

Urine concentrations low

AmBisome can cause acute back or chest pain with first infusion.

Potassium wasting in urine

Question 15

Flucytosine, FYI facts

Answer 15

Flucytosine

 Bioavailability 100%, good levels in CSF, eye, urine

 Accumulates in azotemia: BM
depression, hepatitis, colitis. Measure blood levels/dose.

 Used with ampho in cryptococcal meningitis