Table 1.

Antifungal drug classes, targets and frequently observed mechanisms of resistance.

Drug class	Target pathway	Drug target	Mechanism of action	Mechanism of resistance	Species with reported resistance
Azoles (fluconazole, voriconazole, itraconazole, posaconazole, isavuconazole)	Cell membrane (Ergosterol)	Erg11p (lanosterol 14-α-demethylase)	Inhibits de novo ergosterol synthesis thereby depleting membranes of ergosterol and causing accumulation of toxic sterol precursors	Increased drug efflux Mutations in Erg11p Overexpression of Erg11p Copy number variation Incorporation of non-ergosterol sterols into cell membranes	C. albicans C. glabrata C. tropicalis C. dubliniensis C. parapsilosis C. krusei (intrinsic) C. auris (almost universal)
Echinocandins (caspofungin, anidulafungin, micafungin)	Cell wall (β-1,3-glucan)	β-1,3-glucan synthase	Inhibits β-1,3-glucan synthesis thereby disrupting cell wall stability	Mutations in FKS1/2	C. albicans C. glabrata C. auris
Polyenes (amphotericin B)	Cell membrane (Ergosterol)	Sterols (ergosterol)	Major: Sequesters ergosterol out of membranes. Minor: induces pore formation causing ion leakage	Incorporation of non-ergosterol sterols into cell membranes	C. albicans C. glabrata C. guillermondii C. krusei C. lusitaniae C. auris
Pyrimidine analogues (5- fluorocytosine)	DNA synthesis, Protein synthesis	FUMP, FDUMP	Inhibits pyrimidine metabolism	Mutations in UPRT, FCY1, FCY2, FUR1	C. albicans C. glabrata