Nystatin is an antifungal medication often used to treat superficial infections, but it is generally ineffective against onychomycosis, the technical term for toenail fungus. The fungi responsible for most toenail infections fall outside of Nystatin’s effective range, making this common antifungal an incorrect solution.
The Specific Targets of Nystatin
Nystatin belongs to a class of medications called polyene antifungals, and its mechanism of action is highly specific, targeting a component unique to the cell membranes of certain fungi. The drug works by seeking out and binding to a molecule called ergosterol, which performs the same structural function in a fungal cell membrane that cholesterol performs in a human cell membrane. This binding process is highly disruptive, causing the fungal cell wall to become leaky.
When Nystatin attaches to ergosterol, it forms pores within the membrane, leading to the rapid leakage of essential intracellular contents and causing the fungal cell to die. This mechanism is primarily effective against yeasts, most notably species belonging to the Candida genus. Nystatin is the standard treatment for infections like oral thrush or diaper rash caused by Candida albicans, but it has a very narrow spectrum of activity against other types of fungi.
Primary Causes of Toenail Fungus
The reason Nystatin fails to treat most cases of onychomycosis relates directly to the type of organism causing the infection, which is usually not a yeast. The vast majority of toenail fungus infections, estimated to be over 90% of all cases, are caused by a group of filamentous fungi called dermatophytes. The most common dermatophyte responsible is Trichophyton rubrum, which thrives on keratin, the protein that makes up the nail plate.
Dermatophytes have a different cell wall structure and metabolic pathway compared to the yeasts that Nystatin targets. These organisms are not susceptible to the drug’s pore-forming mechanism, making Nystatin ineffective against the predominant cause of toenail infection. The infection is difficult to treat because the fungus embeds itself deep within the nail bed and the nail plate, requiring medication that can penetrate the dense nail structure.
While rare, some onychomycosis cases can be caused by Candida species, particularly in individuals with underlying health conditions. Even in these instances, Nystatin is often not the preferred treatment because its topical formulations struggle to penetrate the hard, thickened nail plate barrier effectively. Therefore, Nystatin does not work for the typical case of toenail fungus because the causative organism is resistant to its action.
Standard, Effective Treatments for Onychomycosis
Since the infection is typically caused by a dermatophyte embedded deep within the nail, effective treatment protocols must use different classes of antifungals that can reach the infection site. The most successful approach is often systemic, using oral antifungal medications that are delivered to the nail bed through the bloodstream. These systemic treatments are necessary to achieve high enough drug concentrations within the nail unit to eradicate the fungus.
The current gold standard oral treatment is terbinafine, an allylamine antifungal that is highly fungicidal against dermatophytes. Terbinafine works by inhibiting a different enzyme, squalene epoxidase, which is necessary for the fungus to synthesize ergosterol. This leads to a toxic buildup of squalene within the fungal cell, killing the organism. Treatment typically requires taking the medication daily for approximately 12 weeks for toenails.
Another common oral option is itraconazole, an azole antifungal that functions by blocking another step in the ergosterol synthesis pathway. Topical treatments are sometimes used for mild cases or as an adjunct to oral therapy, but they are limited by their poor ability to penetrate the nail. Stronger topical agents, such as ciclopirox or newer lacquers like efinaconazole, must be applied daily for up to a year to be effective, focusing on delivering the active drug through the nail surface.