The incidence of fungal infections has been increasing with the spread of acquired immunodeficiency syndrome (AIDS) and the increased use of broad-spectrum antibiotics that reduce the non-pathogenic bacteria which normally compete with fungi. Fungal infections can occur on the surfaces of the body or, more seriously, within the body; the latter are seen more frequently in immunocompromised patients such as those receiving chemotherapy for the treatment of cancer.
Amphotericin has a very wide spectrum of antifungal activity. It interacts with ergosterol and forms a transmembrane ion channel in the fungal membrane. It affects only fungi because cholesterol, not ergosterol, is the main sterol in human cells. Given orally, it is not well absorbed but acts in the gastrointestinal (GI) tract. It can be given by intravenous infusion and intrathecally. It is eliminated very slowly (over weeks) in the urine. Unwanted effects with parenteral amphotericin are common and can be serious and include renal toxicity, hypokalaemia, anaemia and anaphylactic reactions.
Flucytosine is converted to 5-fluorouracil, an anti-metabolite, within fungal cells. It has a narrow spectrum of action affecting mainly yeast and cryptococcal infections. It is given orally or by intravenous infusion and is widely distributed in the body. Unwanted effects are infrequent.
This group includes imidazoles and triazoles; these are effective in the treatment of a wide range of fungal infections.
Mechanism of action
Azoles inhibit the fungal P450 enzymes that are necessary for the synthesis of ergosterol – an essential component of the fungal membrane. Examples are fluconazole, itraconazole and clotrimazole.
Fluconazole is given orally or intravenously and is widely distributed, passing into the cerebrospinal fluid (CSF) and other bodily fluids. Itraconazole is given orally and undergoes extensive first-pass metabolism.
Unwanted effects of fluconazole are mild; itraconazole can cause GI tract disturbances.
Terbinafine inhibits the synthesis of ergosterol, a crucial component of fungal cell membranes. Given orally, it is selectively taken up by the nails, skin and fat. Unwanted effects are mild.