Fluconazole (often marketed as Diflucan) is a commonly prescribed oral triazole antifungal medication. It functions by disrupting the synthesis of ergosterol, a compound necessary for maintaining the structural integrity of the fungal cell membrane. While highly effective for many fungal infections, particularly those caused by Candida albicans, alternatives are often needed due to patient factors or fungal resistance.
Patient intolerance, concerns over potential side effects like liver enzyme elevation, or contraindications such as pregnancy may necessitate a change in therapy. A significant and growing concern is the emergence of fluconazole resistance, especially in non-albicans Candida species like Candida glabrata and Candida krusei. This resistance requires reliance on alternative medications with different mechanisms of action.
Other Systemic Antifungal Medications
When an infection is systemic, meaning it has spread throughout the body, or involves a fluconazole-resistant strain, treatment requires alternative oral or intravenous (IV) agents. Systemic alternatives often include second-generation triazoles, such as itraconazole, voriconazole, and posaconazole. These azoles offer a broader spectrum of activity than fluconazole, making them effective against a wider range of fungal pathogens, including certain molds and resistant Candida strains.
Voriconazole and posaconazole are frequently reserved for treating severe infections due to their enhanced potency and ability to penetrate various tissues. However, these newer azoles inhibit key liver enzymes involved in drug metabolism, requiring careful monitoring and adjustment of other medications the patient may be taking. Itraconazole is commonly used for infections affecting the nails and skin, but its absorption is highly variable, often requiring it to be taken with food or an acidic beverage.
A different class of antifungals, the echinocandins, is a major alternative for severe, resistant infections. This class includes caspofungin, micafungin, and anidulafungin, which are only administered intravenously. Echinocandins work by targeting \(\beta\)-(1,3)-D-glucan, a component of the fungal cell wall absent in human cells. This unique mechanism makes them fungicidal and highly effective against most fluconazole-resistant Candida species, including C. glabrata.
For life-threatening systemic fungal infections, polyene antifungals, specifically amphotericin B, remain a powerful option. Amphotericin B binds to ergosterol in the fungal cell membrane, creating pores that cause rapid cell death. Modern formulations, such as liposomal amphotericin B, reduce the high incidence of side effects like nephrotoxicity common with older formulations. Although highly effective, its potential for severe side effects means it is usually reserved for the most severe or refractory cases.
Prescription Topical and Local Treatments
For localized fungal infections affecting the skin, mouth, or vagina, prescription-strength topical agents are often preferred to avoid the systemic exposure and side effects associated with oral medications. One established local option is nystatin, a polyene antifungal available as an oral suspension for oral thrush or as a cream or vaginal tablet for localized candidiasis. Nystatin works by binding to ergosterol but is negligibly absorbed into the bloodstream, confining its action to the site of application.
For complicated or recurrent vulvovaginal candidiasis, prescription azole formulations like terconazole or butoconazole are available. These are applied intravaginally for three to seven days, delivering a high concentration of the drug directly to the infection site.
Prescription local treatments are also used for specific dermatological infections where oral fluconazole is not the optimal choice. Fungal nail infections (onychomycosis), for example, can be treated with antifungal lacquers like ciclopirox. Ciclopirox is a hydroxypyridone antifungal that works by chelating polyvalent cations like iron and aluminum, inhibiting metal-dependent enzymes within the fungal cell.
Ciclopirox lacquer is painted directly onto the nail plate, a process that may need to be repeated daily for many months due to the slow growth rate of the nail. This localized delivery method overcomes the poor penetration of thick nail keratin, minimizing the risk of widespread side effects while concentrating antifungal activity.
Non-Prescription and Supportive Care Options
For minor, uncomplicated fungal infections, non-prescription options often serve as the first course of treatment. The most common are over-the-counter (OTC) topical azoles, such as miconazole and clotrimazole, available as creams, ointments, or vaginal suppositories. These products inhibit ergosterol synthesis, similar to fluconazole, but confine the medication to the skin or mucosal surface. These localized OTC azoles are effective for common conditions like athlete’s foot, ringworm, and uncomplicated vaginal yeast infections, providing relief within a few days.
For recurrent vulvovaginal candidiasis, especially those caused by non-albicans species like C. glabrata, boric acid is a non-pharmaceutical option. Boric acid is typically compounded into a gelatin capsule and inserted intravaginally for an extended period. It is hypothesized to work by restoring the acidic vaginal pH and exerting a non-specific antifungal effect against resistant strains. Boric acid is toxic if swallowed and must only be used as a vaginal suppository.
In addition to direct antifungal treatments, supportive care focuses on restoring the body’s natural microbial balance to prevent recurrence. Probiotic supplements containing Lactobacillus species help re-establish beneficial bacteria, which can inhibit Candida overgrowth. While not a primary treatment for acute infection, probiotics and dietary modifications, such as reducing simple sugar intake, are valuable strategies for long-term health maintenance and reducing future fungal issues.