Table 1.

Spectrum of activity and mechanisms of action and resistance of the major antifungal agents enrolled in the treatment of invasive candidiasis.

Antifungal Class	Antifungal Drug	Spectrum of Activity	Mechanism(s) of Action	Mechanism(s) of Resistance
Polyenes	Amphotericin B	Fungicidal	Polyene molecules links to ergosterol in the fungal membrane by inserting into the lipid bilayers, creating pores that disrupt plasma membrane; oxidative damage.	Mutations in the ERG3 gene affect ergosterol biosynthesis and content in the fungal membrane is responsible for a decrease access to the drug target; susceptibility to oxidative damage by increasing catalase activity.
Pyrimidine analogues	5-Flucytosine	Fungicidal	Inhibition of cellular function and division by incorporating toxic fluorinated pyrimidine antimetabolites into DNA and RNA.	Mutations in the enzyme uracil phosphoribosyltransferase (Fur1p), decreasing the formation of toxic antimetabolites.
Azoles	Fluconazole Voriconazole Posaconazole	Fungistatic	Inhibition of the fungal cytochrome P450 14α-lanosterol demethylase and accumulation of toxic methylated intermediates, with resultant disruption of fungal cell membrane function and growth inhibition.	Overexpression of cell membrane efflux pumps, decreasing drug concentration (upregulation or overexpression CDR and MDR genes); alteration of the target enzyme, decreasing affinity to the binding site (point mutation in ERG11 gene); upregulation of the target enzyme (overexpression of ERG11 gene).
Echinocandins	Caspofungin Anidulafungin Micafungin	Fungicidal	Inhibition of β-(1,3) glucan synthase, decreasing the production of β-(1,3) glucan, which represents one of the major components of the fungal cell wall.	Point mutations in FKS1 and FKS2 genes.