Features of Antifungal Agents

AGENT MECHANISM OF ACTION USE POLYENES Nystatin Membrane disruption Most fungi Amphotericin B Membrane disruption Most fungi AZOLES Ketoconazole Cryptococcus, fungib Fluconazole Cryptococcus, fungi Itraconazole Demethylase block of Cryptococcus, ergosterol synthesis fungi, Clotrimazole some yeasts Miconazole some other yeasts Voriconazole some other and molds ALLYLAMINES Terbinafine Squalene accumulation Dermatophytes, azoles for Candida, Aspergillus Naftifine Squalene accumulation Dermatophytes FLUCYTOSINE Cryptococcus, RNA and DNA synthesis Demethylase block of ergosterol synthesis Demethylase block of ergosterol synthesis Demethylase block of ergosterol synthesis Demethylase block of ergosterol synthesis Demethylase block of ergosterol synthesis

MECHANISM OF RESISTANCE ROUTE Sterol modification Sterol modification Topical, I.v

CLINICAL

Active efflux, demethylase

Oral

Candida, dimorphic

alteration, or overproductiona Active efflux, Oral, i.v demethylase alteration, or overproductiona Active efflux, demethylase alteration, or invasive molds overproductiona (Aspergillus) Unknownc Topical

Candida, dimorphic

Oral, i.v

Candida, dimorphic

Candida, other

Unknownc

Topical

Candida,

Unknownc

Oral, I.v

Candida, yeasts

?Active efflux . Unknown Permease or modifying

Oral combined with Topical Oral Candida and

enzymesd absent resistance emerges

or decreased in monotherapy ECHINOCANDINS Caspofungin Block of glucan Candida Synthesis GRISEOFULVIN Microtubule disruption Dermatophytes POTASSIUM IODIDE Unknown schenckii TOLNAFTATE Dermatophytes Unknown Unknown I.v Aspergillus,

Unknown Unknown Unknown

Oral Oral Oral Sporothrix

Abbreviation: 5FC, 5-flucytosine. a Most work is with fluconazole and Candida, other azoles are to be assumed similar. b Generally less absorbed and less active than fluconazole or itraconazole. c Probably similar to other azoles, but resistance to the concentrations in topical preparations may differ. d Cytosine deaminase and uracil phosphoribosyltransferase (the enzyme that forms 5-fluorodoxyuridine from 5FC).