- Cell wall: echinocandins
- Cell membrane (ergosterol)
– Amphotericin B
- Antimetabolite: Flucytosine
- Mitosis inhibitor: griseofulvin
Some pearls on antifungals:
– Ketoconazole, clotrimazole, miconazole, econazole
– The strongest imidazole (comparable to terbinafine) is sertaconazole
– ketoconazole is famous for causing gynecomastia.
– Only fluconazole and posaconazole have good oral bioavailibility and CNS penetration
– Itraconazole and voriconazole have poor oral bioavailibility and CNS penetration.
– Oral fluconazole does not need acidic pH to be absorbed., itraconazole needs acidic condition to be absorbed; so beware in patients taking PPI/antacid/antihistamine
– The wider the spectrum, the more chance of drug-drug interaction.
- Oral terbinafine
– First line for tinea unguium (if it spreads proximally involving the lunula) and capitis.
– However,in kerion griseofulvin is favoured if pityrosporum is the pathogen. Terbinafine is only used if trichophyton is identified as the pathogen.
– Slow onset of action, and has highly variable availibility, making it less effective
– Concentrates in keratinocytes (skin, nail or hair)
- Amphotericin B
– Nephrotoxicity, and hypersensitivity reaction (before infusion need test dose with antihistamine beside)
– Converted to 5-FU by fungal enzyme which blocks DNA formation; therefore mutation in the enzyme can cause resistance
– Typically used with amphotericin B
– Static against Aspergillus but Cidal Against Candidiasis
** Cell membrane inhibitors are fungicidal; BUT griseofulvin is fungistatic
Almost all antifungals are cidal except griseofulvin, flucytosine and echinocandins (towards aspergillus).
- Imidazoles are generally okay againt superficial candidiasis.
- For systemic candidiasis
Fluconazole < newer triazoles < echinocandins, amphotericin B
- Fluconazole: C.krusei and glabrata are resistant.
- For newer triazoles, resistance has been found for C.glabrata.
- Triazoles and amphotericin B are generally effective.
- Fluconazole DOES NOT cover aspergillus.
- Newer triazoles, echinocandins > amphotericin B
- Resistance has been found for A.tereus in amphotericin B.
- Only amphotericin B and posaconazole cover this fungus, with posaconazole > amphotericin B
Histoplasmosis, blastomycosis, coccidiodomycosis
- Amphotericin B and triazoles are generally okay.
So for summary
- Echinocandins or Amphotericin B are the best for candidiasis.
– Triazoles is also appropriate. Resistance has been found for triazoles in C.glabrata.
– Fluconazole can be accepted if it’s not C.krusei OR glabrata.
- Triazoles and echinocandins are the best for aspergillus.
– Amphotericin B is appropriate unless A.tereus.
- ONLY posaconazole and amphotericin B cover mucormycosis (posaco > amphotericin B).
- Cryptococcosis generally responds well to triazoles and amphotericin B.
Russell E. Lewis, PharmD. Current Concepts in Antifungal Pharmacology. Mayo Clin Proc. 2011 Aug; 86(8): 805–817.