Polyenes

Question 1

Polyenes

Answer 1

Amphotericin B
Lipid formulations
Nystatin (topical)

Amphotericin B deoxycholate was standard care for systemic infections due to broad spectrum and lack of alternatives

Notable for toxicities (nephrotoxicity and infusion related reactions)

Three lipid forms were developed
ABCD- Ampho B colloidal dispersion
ABLC- Ampho B lipid complex
LAmB- liposomal Ampho B

Less use now
Still used because of activity against yeasts and many molds
Proven efficacy in understudied disease states
Long history of use

Question 2

Polyenes MOA

Answer 2

Bind to ergosterol in the fungal cell membrane- forming pores in the membrane and leading to leakage of cell contents- leading to eventual cell death

Question 3

Polyenes Spectrum

Answer 3

Good
Most Candida and Aspergillus species
Cryptococcus neoformans
Dimorphic fungi
Many molds

Moderate
Mucorales

Poor
C. lusitaniae
A. terreus

Question 4

Polyenes Adverse Effects

Answer 4

Infusion related reactions 
Fever, chills, rigors can be impressive 
Can be attenuated by premedication with APAP, HC, and sometimes others
LAmB has lowest incidence
ABCD has greatest

Renal
Nephrotoxicity is common
Direct effects on distal tubule and indirect effects through vasoconstriction of afferent arteriole is the cause
Nephrotoxicity leads to wasting of Mg and K (frequently need supplementation)
All lipids forms have less risk than conventional deoxycholate form; LAmB has least risk

Others
Increased transaminases and rash

Question 5

Polyenes Dosing Issues

Answer 5

Deoxycholate generally dosed 0.5-1.5 mg/kg/day

Lipid forms 3-6 mg/kg/day
Clinicians dose the lipid forms equivalently but whether they actually are is debatable

Fatal overdose can occur if deoxycholate doses as lipid

Question 6

Polyenes Important Facts

Answer 6

Nephrotoxicity can be decreased by sodium loading
Administer boluses of NS before and after the infusion
This is an inexpensive and easy way to protect the kidney

To decrease incidence of infusion related reactions, clinicians give APAP, Diphenhydramine, and HC
Meperidine is often given to treat rigors; it has a neurotoxic metabolite that is eliminated renally so be careful of using this drug in patients who develop renal dysfunction

Between lipid forms, differences in efficacy are debatable but in safety do exist
Infusion related- ABCD has worst; LAmB the least
All have less nephrotoxicity than deoxycholate; LAmB has the least

Nystatin only used topically; poor tolerance when given systemically

Question 7

Polyenes Good For

Answer 7

Ampho B drug of choice for cryptococcal meningitis and serious forms of other fungal infections (like those caused by dimorphic fungi and some molds)

Because of broad spectrum, reasonable choice if fungal infection suspected but organism not known (like in febrile neutropenia)

Declined use in candidiasis and aspergillosis (availability of newer safer agents)