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The incidence of fungal infections has been increasing in the human population over the last 15 years, majorly due to increased numbers of cancers and immune-compromised patients, who are at great risk owing to deteriorated immune systems.

Antifungal therapy was previously restricted to the systemically active azoles (such as fluconazole, imidazole and ketoconazole) and the broad-spectrum but toxic antifungal drug amphotericin B. Of late, reformulation of amphotericin B into liposomal delivery systems has improved safety profile for the drug.

Also, a new azole antifungal, voriconazole, and a new class of antifungals, the echinocandins, have been introduced into the pharmaceutical industry, putting forward more options of treatment, and reduced toxicity compared with conventional amphotericin B.

Topical drugs for fungal infections

A number of antifungal drugs are either too toxic or otherwise unsuitable for systemic administration, but they can be used topically to treat fungal infections of the skin and mucous membranes. A large number of drugs are presently available in topical form for fungal infections. All these topically applied drugs have a good margin of safety, and most of them show a great degree of effectiveness.

Topical antifungal drugs are available over the counter and come in various forms which include creams, liquids, powders, aerosol sprays, ointments, and vaginal suppositories. Creams and liquids gain entry into the cracks and crevices where fungi are known to grow, so they are usually the most effective modality for treating fungal infections on the skin. But because powders absorb extra moisture, they are better to use in moist areas of the body, such as between the toes.

Candidal infections of the skin

Treatment of candidal infections of the skin is possible with topical imidazoles (such as clotrimazole, econazole, ketoconazole, etc.), topical terbinafine or nystatin. A benefit of using nystatin is that it is not absorbed from the gut after oral administration thus it can be helpful in curing intestinal candidiasis. Oral candidiasis can be treated with nystatin pastilles or suspension. But candidal infections that do not respond well to topical therapy will require a systemically active azole such as fluconazole. 

Dermatophyte infections of skin

Dermatophyte infections of the skin can be treated with a topical imidazole antifungal such as clotrimazole or miconazole in cream form or by using a shampoo containing an antifungal such as ketoconazole. Nystatin is known to be ineffective for Dermatophytosis.

Pityriasis versicolor

Pityriasis versicolor can be treated with topical imidazole creams to be applied in large quantities, but more conveniently with the use of an antifungal shampoo such as one made with ketoconazole. It should be applied once daily and should be left on the skin for up to five minutes before being washed off. This treatment should be continued for five days. In case topical therapy is unsuccessful especially in case of immune-compromised patients, a systemic azole such as fluconazole can be used.

Topical therapy with amorolfine, tioconazole and undecenoate-containing nail lacquers, paints and creams can treat nail infections in the initial stages of fungal disease.

Vulvovaginal candidiasis

Intravaginal application of topical imidazoles is effective in the treatment of vulvovaginal candidiasis. Women should also apply cream to the vulva as well as insert a pessary or intravaginal cream where possible, as this area is also commonly affected.

Most topical antifungal drugs need four weeks of treatment. But certain infections, particularly the infection in spaces between toes, may take up to six weeks for complete cure. The benefit of using topical antifungal drugs is that these agents are usually well tolerated. Topical antifungal drugs also have no recognized drug-drug or food-drug interactions. The commonest adverse effects are localized irritation (presenting as redness, itch, and a burning sensation) caused by the vehicle or its components.

Systemic drugs for fungal infections

Systemic antifungal drugs are administered by mouth or by injection to treat fungal infections. Fungal infections that occur inside the body or that do not settle down after treatment with creams or ointments may need to be treated with systemic antifungal drugs.

Systemic antifungals are used to treat various fungal infections such as histoplasmosis, aspergillosis and blastomycosis,, which can affect the lungs and other organs. They are also used to treat or prevent fungal infections in immune-compromised people, which include bone marrow or organ transplant patients and people with AIDS.

Systemic fungal infections can take a long time to settle completely, so it is usually obligatory to continue medication for several months, or even for a year or longer. It is imperative to continue the medicine as per the advice of the physician, and should be continued even if symptoms begin to improve. If the drug is stopped before long, the symptoms can reappear.

Oral candidiasis

Systemic anti-candidal treatment is the second-line therapy for oral candidiasis. Fluconazole and itraconazole are used in immune-competent patients. But systemic therapy should be avoided in children. Voriconazole is effective in candidal esophagitis and is given as rescue therapy for candidal infections. It has activity against a broader spectrum of species of Candida as compared with fluconazole.

Severe skin infections

Systemic treatment is indicated in severe, extensive skin infections, or in case of associated systemic infections such as in immune-suppressed people, or in people unresponsive to topical treatment. Systemic drugs such as griseofulvin or terbinafine are used to treat advanced nail infections. Oral terbinafine is only effective against Dermatophyte nail infections and has fungistatic activity against candida albicans.   

Aspergillosis

Aspergillosis, rapidly progressive opportunistic mycoses, is known to most commonly affect the respiratory tract of severely immune-compromised patients and is treated with amphotericin. Recent studies put forth that mortality rate can be reduced by using combination therapy, or liposomal amphotericin B, in place of amphotericin monotherapy. More recently, voriconazole is being used as first-line therapy for serious aspergillus infections and is now considered by most clinical mycologists to be the drug of choice for aspergillus infections in both immune-competent and immune-compromised individuals.

Cryptococcal meningitis

Cryptococcal meningitis is the commonest form of fungal meningitis. Treatment is done with amphotericin, with or without flucytosine. Fluconazole is also said to be especially useful for cryptococcal and coccidioidal meningitis. It can be given alone to AIDS patients with no disturbance of consciousness and is also used as prophylaxis against relapse.

Histoplasmosis

Histoplasmosis can be fatal, particularly in HIV infected patients. Oral administration of itraconazole or ketoconazole can be done in less severe infection and intravenous amphotericin is given for more severe infections.

There are several side-effects associated with systemic antifungal drugs. The common minor side-effects of these drugs include constipation, diarrhea, nausea, vomiting, headache, sleepiness, light-headedness, and facial flushing.

It is important to notice that some systemic antifungal drugs such as oral forms of itraconazole or ketoconazole or the injectable form of miconazole may cause serious and possibly life-threatening liver damage. Therefore it is vital for patients to undergo liver function tests before they start consuming the medicine and as often as their physician recommends while they continue taking it.

Rare severe allergic reactions have been reported with fluconazole. Ketoconazole has caused anaphylaxis in some people after the first dose. Also remember to not to take these antifungal drugs with other drugs unless the physician approves of the therapy in order to avoid drug interactions.

  • medical-dictionary.thefreedictionary.com/Antifungal+Drugs,+Systemic
  • www.healthline.com/galecontent/antifungal-drugs-topical
  • findarticles.com/p/articles/mi_g2601/is_0001/ai_2601000104/
  • www.merck.com/mmpe/sec14/ch180/ch180b.html