Standard antifungal treatment, including role of alternative modalities to administer amphotericin B

Intravenous therapy with amphotericin B remains the standard treatment for established fungal infections in cancer patients, and it is the drug of choice for life-threatening fungal disease such as candidiasis, invasive aspergillosis and that caused by other moulds. The dosing and usage patterns have evolved after nearly 40 years' experience and depend on the infectious organism, the site of involvement and toxicities. Despite this experience, nephrotoxicity and dose-related and infusion-related adverse reactions persist, and relatively little is described about dosing, toxicities and their modification. Management of toxicities is approached by altering drug concentration, infusion rate and salt loading and by the use of premedications, supplemental medications and regional therapy. Inherent and emerging resistance of certain fungal organisms has led to combination therapy of amphotericin B with flucytosine for synergy. Guidelines have been proposed for the standardization of antifungal susceptibility testing for yeasts and are undergoing investigation for moulds. Prevention and/or amelioration of the most limiting toxicity of amphotericin B, renal impairment, has been approached by manipulation of the carrier agent, delivery system or delivery site, and, of these, liposomal incorporation or lipid complexing represent the most promising methods. AmBisome is commercially available in Europe. ABLC, AmBisome, and ABCD all localize to the reticuloendothelial system, have less nephrotoxicity and variable incidences of infusion-related side-effects, and appear to allow higher dosing levels with the potential for greater efficacy than Fungizone. Direct comparison of antifungal activity or toxicities among these products would be of value in determining the relative roles for these formulations in the treatment of fungal infections in cancer and bone marrow transplant patients.