Introduction
Nystatin is a polyene antifungal drug that has broad-spectrum fungicidal and fungistatic activity against a number of yeasts and fungi, most notably Candida species. It is one of the most effective antifungal agents synthesized by bacteria, in this case a strain of Streptomyces noursei, and is closely related to amphotericin B, differing only slightly in structure. Nystatin has a greater antifungal activity than amphotericin B - parenterally administered nystatin, however, is associated with significant toxicity and is not available in a formulation appropriate for systemic use. As it undergoes very little absorption following oral or topical administration, nystatin's efficacy is limited to the treatment/prevention of cutaneous, mucocutaneous, and gastrointestinal fungal infections.
Uses
Nystatin is a polyene ionophore antifungal used to treat cutaneous, mucocutaneous, and gastrointestinal mycotic infections, particularly those caused by Candida species.
Nystatin is available in oral formulations for the treatment and/or prevention of oral candidiasis (a.k.a. thrush), intestinal candidiasis, and anal candidiasis. It is indicated topically for the treatment of vulvovaginal candidiasis and other cutaneous candida infections. A combination product containing nystatin alongside neomycin, gramicidin D, and triamcinolone (Viaderm K.C.®) is indicated in the treatment of corticosteroid-responsive dermatoses caused by bacterial or candidal infections and for pruritus ani/vulvae. It is also available in combination with metronidazole for the treatment of mixed infections due to Trichomonas vaginalis and Candida albicans.
Nystatin is also sometimes used off-label for the prevention of invasive candidiasis in low birth weight neonates, though it is generally reserved as a second-line option after fluconazole.
Associated Conditions
Pharmacodynamics
Nystatin is an antifungal that is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast-like fungi. It exerts its antifungal effects via disruption of the fungal cell membrane. Resistance to nystatin is minimal in Candida albicans, but tends to develop in other species of Candida. Nystatin carries no significant activity against bacteria, protozoa, or viruses. It carries significant systemic toxicity and is currently unavailable in a formula appropriate for systemic use - its efficacy is currently restricted, therefore, to topical, oral, and gastrointestinal infections.
Mechanism of Action
Nystatin is a channel-forming ionophore, meaning it exerts its therapeutic effect via formation of a membrane-spanning pore in the fungal plasma membrane. The formation of this pore results in a change in membrane permeability that allows for leakage of intracellular contents and the subsequent disruption of electrochemical gradients necessary for proper cell function. Selectivity for fungal cells over mammalian cells is due to nystatin’s greater binding affinity for ergosterol, a key sterol found in fungal cell walls, as opposed to its mammalian counterpart, cholesterol.
Absorption
Systemic absorption of nystatin is minimal following oral administration, and no detectable plasma concentrations are attained following topical or vaginal administration.
Volume of Distribution
Nystatin is not absorbed into the systemic circulation and thus does not undergo distribution.
Protein Binding
Nystatin is not absorbed into the systemic circulation and is therefore not subject to plasma protein binding.
Route of Elimination
The majority of orally administered nystatin is eliminated unchanged in the feces.
Toxicity
The oral LD50 in rats is 10 g/kg. There have been no reports of serious toxic effects following overdosage of nystatin - doses in excess of five million units daily have resulted in nausea and gastrointestinal upset with no other associated effects.
Food Interactions
No interactions found.
