Antifungals
Last updated 12th September 2019 - Tom Heaton
There are 3 main classes of antifungal medications:
Antifungal medications target components of the fungal membrane or wall that are unique to fungi.
- Polyenes
- Azoles
- Echinocandins
Antifungal medications target components of the fungal membrane or wall that are unique to fungi.
Polyenes
Polyenes bind to the ergosterol in the cell membrane of the fungi.
This then results in the development of pores that lead to loss of osmotic control of the cell.
Examples include:
This then results in the development of pores that lead to loss of osmotic control of the cell.
Examples include:
- Amphotericin B deoxycholate
- AmBisome (liposomal amphotericin B)
- Nystatin
Amphotericin B
Initially isolated from the bacteria streptomyces nodosus.
It has a wide range of antifungal activity:
It has significant toxicity though:
It has strong protein binding and so tissue penetration can be poor
The lipid formulations e.g. AmBisone are thought to reduce the toxicity of the drug by limiting its action to the site of the fungi.
It has a wide range of antifungal activity:
- Candida (most species)
- Cryptococcus
- Aspergillus (most species)
- Dimorphic fungi
It has significant toxicity though:
- Nephrotoxic
- Electrolyte derangement
- Hypokalaemia
- Hypomagnesaemia
- Hypokalaemia
- Infusion reactions
- Nausea/vomiting
- Chills/rigors
- Nausea/vomiting
- Phlebitis
- Anaemia
It has strong protein binding and so tissue penetration can be poor
The lipid formulations e.g. AmBisone are thought to reduce the toxicity of the drug by limiting its action to the site of the fungi.
Azoles
Azoles act by inhibiting the enzyme 14,alpha-demethylase.
This is a key enzyme in the synthesis of ergosterol.
There is subsequently reduced ability to reproduce, even if the result may not be death of the fungi.
It is important to note that this mechanism of action may actually impede the efficacy of polyenes.
Examples include:
There is quite a variation in activity of the different azole against different fungal species.
A basic summary of indications:
Fluconazole
Adverse effects include:
This is a key enzyme in the synthesis of ergosterol.
There is subsequently reduced ability to reproduce, even if the result may not be death of the fungi.
It is important to note that this mechanism of action may actually impede the efficacy of polyenes.
Examples include:
- Fluconazole
- Itraconazole
- Voriconazole
- Clotrimazole
There is quite a variation in activity of the different azole against different fungal species.
A basic summary of indications:
Fluconazole
- First line for most candida
- Can be a step down for cryptococcus
- Mild-moderate coccidioidomycosis
- Dimorphic fungi
- Invasive aspergillus (may also add echinocandin)
Adverse effects include:
- Numerous drug interactions (warfarin, anticonvulsants)
- Hepatotoxicity
- Alopecia - fluconazole
- Neurotoxicity - voriconazole
- Headaches
- Nausea/vomiting and abdominal pain
- Stevens-Johnson syndrome
Echinocandins
Echinocandins inhibit the enzyme beta-1,3-glucan synthase, which is a key enzyme in the synthesis of beta-1,3-glucan in the cell wall.
Beta-1,3-glucan can be thought of as equivalent to the peptidoglycan of bacterial cell wells, and this echinocandins as the penicillin of antifungals.
This can be fungicidal (e.g. in candida species) or simply fungistatic (e.g. in aspergillus).
Examples include:
The indications are:
Minor adverse effects include:
Beta-1,3-glucan can be thought of as equivalent to the peptidoglycan of bacterial cell wells, and this echinocandins as the penicillin of antifungals.
This can be fungicidal (e.g. in candida species) or simply fungistatic (e.g. in aspergillus).
Examples include:
- Caspofungin
- Anadulafungin
- Micafungin
The indications are:
- Treatment of candida when azoles not suitable
- Second line for aspergillus disease
Minor adverse effects include:
- Rash
- Diarrhoea
- Arthralgia
Links & References
- Strong Medicine. Antifungals (fungal infections - lesson 4). Youtube. 2015. https://www.youtube.com/watch?v=qkmF-kA0AR8
- Beed, M. et al. Fungal infections and critically ill adults. CEACCP. 2014. 14(6). 262-267. https://academic.oup.com/bjaed/article/14/6/262/247636
- Lockwood, G. Antimicrobial drugs. e-LFH. 2019.