Echinocandins

Question 1

Echinocandins

Answer 1

Caspofungin
Micafungin
Anidulafungin

Their MOA is distinct

Three drugs have virtually identical spectra

Very well tolerated

Excellent activity against Candida

Lack an oral formulation

Considerably fewer drug interactions than azoles
Safer than polyenes
Great activity against fluconazole resistant yeasts

Question 2

Echinocandins MOA

Answer 2

Inhibit beta-1,3-D-glucan synthase- the enzyme responsible for production of beta-1,3-D-glucan (a vital component of the cell wall of many fungi)
Only active against fungi that are dependent on this type of glucan

Question 3

Echinocandins Spectrum

Answer 3

Good
C. albicans
C. glabrata
C. lusitaniae 
C. parapsilosis 
C. tropicalis 
C. krusei
Aspergillus species 

Moderate
C. parapsilosis
Some dimorphic fungi
Mucorales (in combo with AmphoB)

Poor
Most non-Aspergillus molds
Cryp. neoformans

Question 4

Echinocandins Adverse Effects

Answer 4

Excellent safety profile

Can cause mild histamine-mediated infusion related reactions (not common and can be ameliorated by slowing the infusion rate)

Hepatotoxicity is also possible with any of these but not common

Question 5

Echinocandins Important Facts

Answer 5

Differences between agents are minor; mostly PK

Caspofungin and Micafungin eliminated hepatically (noncytochrome P450)
Anidulafungin degrades in plasma; avoids hepatic metabolism (but not completely devoid of hepatotoxicity)

Have excellent cidal activity against Candida; against Aspergillus activity is neither classically cidal or static (cause aberrant nonfunctional hyphae to be formed by the actively growing mold)

Only modestly active against molds; substantially enhance effects of other antifungals against these pathogens; trend toward reduced mortality among combo therapy (p value = 0.07 in this study; there is low toxicity with echinocandins so clinicians still advocate for combo therapy)
May also enhance effects of LAmB against Mucorales (based on in vitro and limited clinical data)

Drug interactions are minor
Take caution:
Caspofungin (with cyclosporine)
Micafungin (with Sirolimus)

Are not cheap and are IV only
After beginning empiric therapy with echinocandin, consider switching to fluconazole of susceptible strain and no contraindications to fluconazole

Question 6

Echinocandins Good For

Answer 6

Drugs of choice for invasive candidiasis (especially in patients who are clinically unstable and at risk for azole resistant species)

Useful in invasive aspergillosis (do not have as much supporting data as voriconazole and the polyenes)

All used for esophageal candidiasis
Some used for prophylaxis or empiric therapy of fungal infections in neutropenic patients

To increase likelihood of cure, will add echinocandin to:
Voriconazole (for Aspergillus)
AmphoB (for Mucorales)