Azoles
Class Summary
Azoles are synthetic antifungals with broad-spectrum fungistatic activity against yeasts and fungi, including candidal species. By blocking fungal cytochrome P450-dependent enzymes, azoles disrupt the synthesis of ergosterol, which is the principal sterol in fungal cell membranes. The two subclasses of azoles are imidazoles (eg, clotrimazole, miconazole, econazole, ketoconazole) and triazoles (eg, fluconazole, itraconazole).
The most common adverse effect of topical azoles is local skin and mucous membrane irritation. The most common adverse effects of systemic azoles are gastrointestinal distress, morbilliform rash, and hepatotoxicity. Most azoles have additional adverse effects specific to each drug, and these are listed below. Diazoles (eg, ketoconazole, miconazole) have a stronger effect on human cytochromes than triazoles (eg, fluconazole, itraconazole) and therefore tend to have more severe adverse effects. Caution must be exerted when prescribing azoles to patients who take other medicatons that are metabolized by the cytochrome P450 system. Azole-induced inhibition of the cytochrome complex may increase plasma concetration of these medicatons (e.g. warfarin).
Azoles are effective antifungals, but resistance is occasionally reported. Development of cross-resistance of C albicans to different azoles during treatment with a single azole derivative has been described. Second-generation triazoles, such as voriconazole or posaconazole, offer greater succeptibility rates and hold indications for the use of mucocutaneous candidias in certain settings. [23, 24]
Clotrimazole (Lotrimin, Mycelex, Femizole, Gyne-Lotrimin)
Clotrimazole is available as topical therapy. As a 10-mg troche, clotrimazole is effective against oral candidiasis in some patients who are immunocompromised. It is less effective than other azoles in patients with HIV infection.
Fluconazole (Diflucan)
Fluconazole is available as systemic therapy. Compared with other azoles, it has lower toxicity while maintaining a half-life of 30 hours in patients with normal renal function. Fluconazole is active against most C albicans, although resistance is occasionally seen. It is less active against other species, such as C glabrata, and it has no activity against C krusei.
Itraconazole (Sporanox)
Itraconazole is available as systemic therapy. Itraconazole is active against all Candida species. Therefore, it may be advantageous in patients who are immunocompromised and in whom other antifungals may predispose to selection and overgrowth of resistant species. It may interact with terfenadine, astemizole, and cisapride to produce dysrhythmias and to increase the activity of anticoagulants, cyclosporine, midazolam, and sulfonylureas. Adverse effects include hepatotoxicity, hypokalemia, and peripheral neuropathy.
Voriconazole (Vfend)
Voriconazole is available as systemic therapy. It holds several labeled indications, include those for the treatment of disseminated cutaneous candidiasis and esophgeal candidiasis. It is effective against organisms that demonstrate resistance to fluconazole, including C krusei and C glabrata. There are reports of voriconazole-resistant C. glabrata isolates across a wide geographical range. If available and indicated, testing of candidal isolates for antifungal succeptibilities should be considered. The associated adverse effects include phototoxicity, arrhythmia, and visual disturbances.
Posaconazole (Noxafil)
Pasoconazole is a newer, 2nd-generation triazole that is thought to have a more favorable side effect profile as compared to earlier azoles. Although it is generally used for prophylaxis and treatment of invasive Aspergillus or Candidal infections, there is an oral suspension that is FDA-approved for the treatment of oropharyngeal candidiasis, including cases that are refractory to itraconazole or fluconazole.
Polyenes
Class Summary
This class of antifungals includes the drugs amphotericin B and nystatin. Amphotericin B is available as a systemic therapy, and nystatin is available as topical therapy. Polyenes irreversibly bind to the cell membrane sterol, ergosterol, causing disruption by increasing cell membrane permeability. They are fungistatic at low concentrations and become fungicidal at higher concentrations.
Amphotericin, in particular, is notorious for its adverse effects. It can cause fevers, electrolyte disturbances, nephrotoxicity, arrhythmias, as well as a number of skin eruptions. Severe reactions from amphotericin include seizures, agranulocytosis, and hepatotoxicity.
Amphotericin B deoxycholate (Amphotericin B (conventional), Fungizone)
This is one of the oldest antifungals and has been in use for more than 40 years; it is the criterion standard of antifungal therapy. Lipid formulations have been developed. The total dose must be adjusted depending on the type of candidal infection being treated. Most patients receive a total dose of 0.5-1.5 g.
Nystatin (Mycostatin, Nilstat, Nyamyc)
This is a fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. It is effective against various yeasts and yeastlike fungi. It changes the permeability of the 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.
Topical Antimicrobials
Class Summary
Silver sulfadiazine (Silvadene, SSD Cream, Thermazene)
Silver sulfadiazine (SSD) applied topically to the skin exhibits antimicrobial effects; although it is not used on mucosal surfaces, SSD has been incorporated into resins used to create dentures and other dental materials, in which it promotes anti-adhesive properties that are thought to control microbial growth.
Boric acid
Boric acid is an inexpensive white crystalline solid that is thought to have fungistatic properties. It may be obtained through a compounding pharmacy and has been used in the treatment of azole-resistant candidal vulvovaginitis. Adverse effects can be mild, such as local irritation. Systemic adverse effects can also occur and can include fever, vomiting, and seizures. Patients should be warned that boric acid capsules can be fatal if swallowed, and they should not be used during pregnancy.
Gentian violet 1%
When applied topically, gentian violet has antiseptic properties. A case of successful treatment of C glabrata vulvovaginitis has been reported.
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Pseudomembranous candidiasis.
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Erythematous candidiasis in HIV/AIDS.
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Denture-related stomatitis; a common form of oral candidiasis. From Scully C, Flint SF, Bagan JV, Porter SR, Moos K. Atlas of Oral and Maxillofacial Diseases. 2010. Informa, London.
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Angular cheilitis; a common form of oral candidiasis, typically seen in patients with denture-related stomatitis, especially those in whom the denture needs adjustment. In others, it may be a sign of diabetes, nutritional deficiency, or immune defect.
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Multifocal candidiasis; lingual lesions.
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Chronic hyperplastic candidiasis; typically affects the tongue dorsum or the commissures of the lips; potentially malignant.
