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Antifungal Therapy

Antifungal therapy

Definition

Antifungal drugs are used to treat infections caused by fungus and to prevent the development of fungal infections in patients with weakened immune systems.

Purpose

Fungal infections

A fungus is a living organism that can cause infection when it grows in the human body. In healthy people, fungal infections tend to be mild and treatable. For cancer patients, however, fungal infections can become severe and must be treated quickly. Cancer patients, particularly those with leukemia or lymphoma , tend to have weakened immune systems as a result of chemotherapy or the disease. Once they are infected, their weak immune system allows the fungus to grow quickly. Because of this risk, some cancer patients with no obvious fungal infection are given antifungal therapy to help prevent infection from developing.

Fungal infection can occur in two ways. Some fungi, such as candida, are usually found in the bodies of healthy people and cause little or no harm. When the immune system is weak, however, these fungi begin to grow and cause infection. Other fungi, such as aspergillus and cryptococcus, are found in the air. Infection occurs when the fungus is either inhaled into the lungs or comes into contact with an operative wound. The most common fungal infections found in patients with weakened immune systems are candidiasis, aspergillosis and cryptococcosis.

Treatment

The treatment of a fungal infection depends on the type and location of infection. Superficial infections that affect the skin, hair, and nails can be treated with topical (cream or ointment) or oral antifungal drugs. Systemic infections that affect the internal organs require aggressive treatment with either oral or intravenous drugs.

Description

There are three classes of drugs typically used to treat fungal infections: polyenes, azoles, and echinocandins.

Polyenes

Polyenes are drugs that work by attaching to the sterol component found in the fungal membrane, causing the cells to become porous and die. The two polyenes most commonly used are nystatin (Mycostatin) and amphotericin B (Fungizone). Nystatin is often used as a topical agent to treat superficial infections, or is taken orally to treat candidal infections such as oral or esophageal candidiasis.

Amphotericin B was the first antifungal drug to be approved for use, and it is still the standard therapy for the most severe systemic fungal infections. Recently, several new types of amphotericin B (Abelcet, Amphotec and AmBisome) have been introduced. These drugs, called lipid formulations, cause fewer side effects than traditional amphotericin B but are more expensive.

Azoles

Azoles stop fungal growth by preventing fungi from making an essential part of their cell wall. Three typical azoles are ketoconazole (Nizoral), fluconazole (Diflucan), and itraconazole (Sporanox). Ketoconazole is the oldest of these three drugs, and has been used since the 1970s. It is slightly more toxic than the other azoles and does not work for aspergillosis and many candidiasis infections.

Although fluconazole is effective against both superficial and systemic candidiasis, some strains of this fungus have now become resistant to the drug. Itraconazole, the newest of the azoles, is effective against a range of different fungal infections. Unlike ketoconazole or fluconazole, it can be used to treat aspergillosis.

Echinocandins

Echinocandins are a new class of antifungal drugs that work by disrupting the wall that surrounds fungal cells. Caspofungin (Cancidas) is the first of this new class of drugs to be approved. It is an effective treatment for severe, systemic fungal infections, and is given to patients who do not respond to other therapies.

Recommended dosage

Although dosages differ for the various antifungal treatments, most therapies continue even after there is no sign of infection.

Polyenes

Topical nystatin should be liberally applied two to three times daily. Liquid formulations of the drug are usually taken in doses of 400, 000 to 600, 000 units four times a day for adults and children. The dose for the oral tablets is 500, 000 to 1 million units every 8 hours. Both traditional amphotericin B and the new lipid formulations of the drug are given intravenously. Dosages are adjusted according to each patient's tolerance and the severity and location of the infection. Patients receiving amphotericin B treatment are usually hospitalized.

Azoles

Ketoconazole is available as a tablet and as a topical treatment. Both treatments are usually given once daily. Treatment can last for several weeks for superficial infections, or up to a year for more serious infections. Fluconazole and itraconazole are both administered either orally or intravenously. The dose depends on the type of fungal infection, the patient's condition and the response to treatment.

Echinocandins

Caspofungin is given intravenously once daily, and most patients receive the same dose.

Precautions

Patients who are given topical or oral antifungal therapy should make sure they use their medication regularly, and for as long as their doctor thinks is necessary. Infections that are not completely eradicated frequently recur.

Side effects

Antifungal drugs that are applied topically rarely cause side effects unless the patient is allergic to the drug. Side effects are more common when drugs are taken orally or intravenously. The most common reactions from azole drugs are nausea, diarrhea and other gastrointestinal symptoms. These symptoms usually affect less than 10% of patients. Caspofungin also produces few side effects. The most common side effect is a rash.

Amphotericin B can be quite toxic and most patients experience side effects. These include fever , rigors, and chills. Premedication with acetaminophen, diphenhydramine , hydrocortisone, and sometimes meperidine can be given to prevent these side effects. Amphotericin B can also seriously damage the kidneys. However, patients are carefully monitored while taking this drug. If symptoms develop, the liposomal alternative is usually given. Lipid formulations of amphotericin B are far less damaging to the kidneys.

Interactions

Drug interactions are significant with antifungal treatment. Patients taking amphotericin B should not take any other drug that can cause kidney damage. Potentially serious reactions can occur when patients taking azole antifungal therapies also take certain antihistamines such as astemizole (Hismanal) or the statin drug lovastatin (Mevacor). Patients on antifungal therapy who plan to take other prescribed, over the counter, or alternative medicines should always check with their doctor first.

Alison McTavish, M.Sc.

KEY TERMS

Aspergillosis

A fungal infection that can be life-threatening to patients with a weakened immune system.

Candidiasis

A fungal infection that can be mild or very serious depending on what part of the body it infects.

Cryptococcosis

A fungal infection that can cause meningitis.

Intravenous

A treatment that is given directly into the bloodstream.

Topical

A treatment that is applied on the skin.

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