Medication SummarySuccessful therapy for serious systemic Candida infections requires initiation of antifungal therapy as early as possible, as soon as adequate culture results are obtained. Show
Different classes of antifungals are now available to manage any type of candidal infection. Azoles, fluconazole in particular, [39] have become the mainstay of therapy over the past few years. These include topical and systemic agents. Posaconazole is the most recent addition to this group of antifungals. Polyenes include amphotericin B, liposomal amphotericin B formulations, and topical nystatin. Allylamines include terbinafine, which is formulated in a topical preparation and an oral tablet. The newest group of antifungals is echinocandins, including caspofungin, micafungin, and anidulafungin. These drugs have shown excellent clinical efficacy, a low incidence of adverse events, a good safety profile, and ease of use. [48, 49]  Azole AntifungalsClass SummaryThese agents are synthetic compounds that include 2 groups, imidazoles and triazoles. Triazoles have 3 atoms of nitrogen in the azole ring. Imidazoles have only two. The primary mechanism of action is inhibition of lanosterol 14-alpha-demethylase, an enzyme required for the synthesis of ergosterol, the main component of fungal cell membranes. Imidazole agents include miconazole, ketoconazole, and clotrimazole. In August 2013, the FDA announced that clinicians should no longer prescribe ketoconazole (Nizoral, Janssen Pharmaceuticals) tablets as a first-line therapy for any fungal infection, including Candida and dermatophyte infections, because of the risk for severe liver injury, adrenal insufficiency, and adverse drug interactions. [34, 35] The FDA also cautioned that ketoconazole tablets should not be prescribed for any patient with underlying liver disease. The labeling changes do not apply to topical formulations of ketoconazole in creams, shampoos, foams, and gels. Oral ketoconazole is now indicated only for endemic mycoses in patients who fail to respond to or cannot tolerate other treatments. Ketoconazole tablets were also withdrawn from the market in the European Union in July 2013. [34, 35] Triazole agents, which are now the most commonly used azoles, include fluconazole, itraconazole, econazole, terconazole, butoconazole, and tioconazole. Newer triazoles (ie, voriconazole, posaconazole, ravuconazole) are active against fluconazole-resistant strains of Candida. Voriconazole and posaconazole have shown high efficacy against candidiasis in recent clinical trials. [43, 50, 51] Topical agents are frequently used as front-line agents to manage localized or superficial forms of candidiasis such as cutaneous candidiasis, oropharyngeal candidiasis (OPC), and vulvovaginal candidiasis (VVC). These preparations are available as a cream for topical use, as troches for OPC, and as a vaginal suppositories or tablets for vaginitis. Fluconazole (Diflucan)
Triazole with less effect on human sterol metabolism. Does not decrease cortisol and testosterone levels, as occurs with ketoconazole. Has fewer adverse effects and better tissue distribution than older systemic imidazoles. Available PO/IV and has demonstrated efficacy in topical and invasive forms of candidiasis. Available in 50-, 100-, 150-, and 200-mg tabs. Daily dose varies with indication. Itraconazole (Sporanox)
Has fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P450-dependent synthesis of ergosterol, a vital component of fungal cell membranes. Effective against broad range of fungi, including Candida species, and is indicated for treatment of cutaneous, oral, esophageal, and disseminated candidiasis. Available IV, 100-mg caps, and oral solution at 10 mg/mL. Caps require gastric acidity for absorption and should be taken with food to increase absorption. Liquid formulation increases bioavailability and decreases need for acidity for proper absorption. Use of solution has been recommended in mucosal and invasive candidiasis, while caps can be used in onychomycosis and dermatophyte infections. Voriconazole (Vfend)
Available as tablet, suspension and parenteral preparations. Effective as fluconazole against esophageal candidiasis, and as effective as amphotericin B deoxycholate in treatment of candidemia and invasive candidiasis. In Europe, it has been approved for "treatment of fluconazole-resistant serious invasive Candida infections (including C krusei)." Additionally, associated with fewer breakthrough fungal infections when used as empiric therapy in febrile neutropenic patients. FDA approved for esophageal candidiasis and candidemia. Posaconazole (Noxafil)
Novel triazole antifungal agent. Blocks ergosterol synthesis of cell membrane by inhibiting enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. Action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Approved for treatment of OPC, including OPC refractory to itraconazole and/or fluconazole and for prophylaxis of infections due to Candida and Aspergillus in patients who are at high risk, such as those undergoing stem cell transplants with graft versus host disease or with prolonged neutropenia due to a hematologic malignancy or its treatment. Glucan synthesis inhibitors (echinocandins)Class SummaryThese agents inhibit the formation of fungal cell wall. The antifungal class has expanded with the approvals of caspofungin, micafungin, and anidulafungin. Indications are evolving but have been approved for complicated forms of invasive candidiasis, candidemia, disease refractory to other systemic antifungals, and intolerance to amphotericin B. They are broad spectrum and fungicidal against most Candida species, except C parapsilosis and C guilliermondii. Caspofungin (Cancidas)
FDA approved to treat candidemia, invasive candidiasis, and esophageal candidiasis. Initially approved to treat refractory invasive aspergillosis. Also approved as empiric therapy for presumed fungal infections in febrile neutropenic patients. First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of (1,3) β -D-glucan, an essential component of fungal cell wall. This component is not found in mammalian cell walls. Micafungin (Mycamine)
A member of a new class of antifungal agents, echinocandins, that inhibit cell wall synthesis. Echinocandins inhibit the synthesis of (1,3)-β -D-glucan, an essential component of the fungal cell wall, not present in mammalian cells. Indications include prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation, treatment of esophageal candidiasis, candidemia, and invasive candidiasis. Anidulafungin (Eraxis)
One of the newer antifungal agents belonging to the echinocandin class. Also inhibits synthesis of (1,3)-β -D-glucan, an essential component of fungal cell walls. Indicated for treatment of esophageal candidiasis, candidemia, and other forms of candidal infections (eg, intra-abdominal abscesses, peritonitis). PolyenesClass SummaryThese are broad-spectrum fungicidal agents. Mechanism of action is by insertion into fungal cytoplasmic membrane, causing increases in permeability. Membrane channel activity is increased at lower doses, and pores are formed at higher concentrations. Amphotericin B (Fungizone, Amphocin)
One of the oldest antifungals, in use for more than 40 y, and the criterion standard of antifungal therapy. In recent years, lipid formulations have been developed. Total dose must be adjusted depending on type of candidal infection being treated. Most patients receive total dose of 0.5-1.5 g. Amphotericin B, lipid formulations (Amphotec, Abelcet, AmBisome)
Novel lipid formulations of amphotericin B that deliver higher concentrations of drug with a theoretical increase in therapeutic potential and decreased nephrotoxicity. Formulation types include amphotericin B lipid complex (ABLC, Abelcet), amphotericin B colloidal dispersion (ABCD, Amphotec), and liposomal amphotericin B (L-AMB, AmBisome). ABLC and ABCD approved for treating adults and children intolerant of conventional amphotericin B or with fungal infections refractory to conventional amphotericin B. L-AMB is approved for aspergillosis, candidiasis, cryptococcosis, and neutropenic patients with persistent fever on broad-spectrum antibiotics. Nystatin (Mycostatin)
Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. Effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak. Membrane channel activity is increased at lower doses, and pores are formed at higher concentrations. AntimetaboliteClass SummaryFlucytosine is an antimetabolite originally developed for the treatment of leukemia. Flucytosine (Ancobon)
It is deaminated to 5-fluorouracil in the fungal cell by an enzyme not present in mammalian cells, and inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B. It has been used in studies in invasive candidiasis. Avoid use as single agent because of ability to quickly develop resistance in vivo. Topical azolesClass SummaryThese agents are used extensively to treat common mucocutaneous uncomplicated forms of candidiasis. Clotrimazole (Mycelex, Femizole-7)
Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Butoconazole (Femstat-3, Gynazole-1)
Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Use 2% vaginal cream. Available OTC. Miconazole vaginal (Monistat, Micatin)
Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out, resulting in fungal cell death. Lotion preferred in intertriginous areas. If cream is used, apply sparingly to avoid maceration effects. Tioconazole (Vagistat-1)
Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out, resulting in fungal cell death. Terconazole vaginal (Terazol-7, Terazol-3)
Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out, resulting in fungal cell death. AllylaminesClass SummaryThese agents cause a deficiency of ergosterol within the fungal cell wall, causing fungal cell death. Terbinafine (Daskil, Lamisil)
For treatment of paronychia; allylamine antifungal, which inhibits squalene epoxidase and decreases ergosterol synthesis, causing fungal-cell death. Use medication until symptoms significantly improve. Duration of treatment should be >1 wk but not >4 wk. May not be as effective for candidal infections as azole antifungals. Antifungals, SystemicIbrexafungerp (Brexafemme)
The first and only treatment for vaginal yeast infections, which is both oral and non-azole, approved for the treatment of VVC. It is a triterpenoid antifungal agent that inhibits glucan synthase, an enzyme involved in the formation of 1,3-beta-D-glucan, an essential component of the fungal cell wall.
Author Jose A Hidalgo, MD Assistant Professor, Universidad Nacional Mayor de San Marcos; Attending Physician, Department of Internal Medicine, Division of Infectious Diseases, Guillermo Almenara Hospital, Peru Jose A Hidalgo, MD is a member of the following medical societies: HIV Medicine Association, Infectious Diseases Society of America Disclosure: Nothing to disclose. Coauthor(s) Jose A Vazquez, MD, FACP, FIDSA Chief, Division of Infectious Diseases, Professor, Department of Medicine, Medical College of Georgia at Augusta University Jose A Vazquez, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Society for Microbiology, HIV Medicine Association, Immunocompromised Host Society, Infectious Diseases Society of America, International AIDS Society, International Immunocompromised Host Society, International Society for Human and Animal Mycology, International Society for Infectious Diseases, Medical Mycological Society of the Americas, Michigan Infectious Disease Society, Mycological Society of America, National Foundation for Infectious Diseases Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cidara; Amplyx; F2G, Scynexis<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan; Astellas. Specialty Editor Board Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Received salary from Medscape for employment. for: Medscape. Chief Editor Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation Disclosure: Nothing to disclose. Additional Contributors David Hall Shepp, MD Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America Disclosure: Received salary from Gilead Sciences for management position. Which antifungal agent is available for systemic and topical use?Azoles are available for topical, oral, and intravenous administration. Common agents include fluconazole, miconazole, itraconazole, and voriconazole.
Which of the following antifungal drugs is used for systemic mycoses?The polyene antifungal, amphotericin B, is widely used as a systemic agent for the treatment of systemic mycoses, such as aspergillosis and candidosis.
What antifungal medication is available for topical administration?The most commonly used topical antifungals include nystatin, tavaborole, ciclopirox, and azoles like ketoconazole, miconazole, econazole, and efinaconazole. These medications are applied topically on the affected skin, in the form of ointments, creams, gels, or foams.
Which antifungal drug is only used as topical application?Nystatin is the only polyene antifungal that is available for topical administration. The drug is derived from Streptomyces noursei and has activity against Candida but not dermatophytes. Nystatin is used topically for the treatment of Candida infections of the skin and mucous membranes.
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